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1.
Am J Physiol Gastrointest Liver Physiol ; 327(4): G485-G498, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39259911

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.


Assuntos
Dieta Hiperlipídica , Hepatócitos , MicroRNAs , Neuregulina-1 , RNA Circular , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Camundongos , Hepatócitos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Masculino , Neuregulina-1/genética , Neuregulina-1/metabolismo , Camundongos Endogâmicos C57BL , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Ribonucleosídeo Difosfato Redutase
2.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4069-4077, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39307739

RESUMO

This study investigates the therapeutic effect of hybrid exosomes loaded with sinomenine(SIN) obtained by membrane fusion of milk exosomes with liposomes in collagen-induced arthritis(CIA) rats. Exosomes were isolated from fresh bovine milk by sucrose density gradient centrifugation, while liposomes were prepared using the emulsion solvent evaporation-low temperature curing method. Hybrid exosomes were characterized after membrane fusion through co-incubation: The morphology was detected by transmission electron microscopy, the particle size and potential by nanoparticle size potentiostat, and the expressions of surface characteristic proteins CD63 and TSG101 before and after fusion by Western blot(WB). The drug loading capacity and encapsulation rate of sinomenine were measured after the loading of sinomenine on exosomes by ultrasonic method. The CIA rat model was induced by collagen antibody. The efficacy experiment consisted of the control group, model group, SIN group, SIN-liposome group, SIN-milk exosome group, SIN-hybrid exosome group and positive drug(dexamethasone) group. The changes in body mass of rats during administration were recorded. Besides, the foot swelling, immune organ index, arthritis index, microcirculation index, synovial histopathology, and serum inflammatory factor levels detected by enzyme-linked immunosorbent assay were observed for pharmacodynamical study. Under transmission electron microscopy, both hybrid exosomes and milk exosomes showed saucer-like appearance. After co-incubation, the exosome particle size increased from(97.92±3.42)nm to(132.70±4.07)nm, and the Zeta potential changed from(-2.01±0.33)mV to(-17.90±2.13)mV. WB assay showed that CD63 and TSG101 proteins were normally expressed in milk exosomes and hybrid exosomes. The encapsulation rate of milk exosomes was 31.64%±2.48%, with a drug loading of 2.35%±0.52%, while the hybrid exosomes exhibited an encapsulation rate of 48.21%±3.12% and drug loading of 3.17%±0.36%, as determined by the microplate reader. Pharmacodynamic results showed that compared with the model group, the general condition, swelling degree of foot, arthritis index and immune organ index of all drug administration groups were significantly improved(P<0.05, P<0.01); microvascular comprehensive score and vascular resistance were significantly decreased(P<0.05, P<0.01); serum levels of TNF-α, IL-1ß and IL-6 inflammatory factors were significantly decreased(P<0.01); and the lesions of synovial tissue were improved to some extent. Meanwhile, compared with the SIN group, SIN-liposome group and SIN-milk exosome group, the SIN-hybrid exosome group had a more stable and durable drug effect. The hybrid exosomes obtained by co-incubation of milk-derived exosomes with liposomes successfully improved the drug carrying capacity of exosomes and biocompatibility of liposomes. The hybrid exosomes loaded with sinomenine have good efficacy on CIA model rats, and can effectively solve the problems of TCM such as sinomenine, which have good efficacy but short biological half-life. The study provides new insights for the development of TCM and the treatment of diseases such as rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Exossomos , Lipossomos , Leite , Morfinanos , Animais , Exossomos/química , Ratos , Lipossomos/química , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Leite/química , Bovinos , Morfinanos/química , Morfinanos/administração & dosagem , Morfinanos/farmacologia , Masculino , Humanos , Feminino
4.
Huan Jing Ke Xue ; 45(9): 5003-5014, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323120

RESUMO

Clarifying the temporal and spatial changes in the carbon budget in the Chongqing metropolitan area and exploring the spatial correlation of land use carbon budget are of great significance for realizing the regional "double carbon" goal. Using 21 districts and counties in Chongqing metropolitan area as the research scale, the IPCC inventory method, carbon emission coefficient method, Gini coefficient, gravity model, and social network analysis were used to estimate the net carbon emissions from land use in Chongqing metropolitan area from 2000 to 2020, and the spatial correlation of the carbon budget was obtained. The results revealed that: ① In the past 20 years, the carbon budget of the Chongqing metropolitan area showed an overall upward trend, with an average annual growth rate of 2.83%, and the spatial distribution was "higher in the north and south, higher in the east and west, and lower in the middle." ② During the past 20 years, the spatial difference of net carbon emissions in the Chongqing metropolitan area became highly average, and the overall Gini coefficient decreased by 11.42%, whereas the intra-group difference was the largest in key development zones. ③ In the past 20 years, the overall structure of the spatial correlation network of land use carbon budget in the Chongqing metropolitan area has become stable and complex, and the network density and network correlation number have increased by 0.43 and 180, respectively, the network correlation degree has increased to 1, and the network health degree has improved. ④ In the individual network structure of land use carbon budget in the Chongqing metropolitan area, the degree centrality of each district and county has increased, and the increase in the central urban area was the most significant, with an increase of 81, whereas the decline in intermediate centrality and proximity centrality has promoted the regional coordinated development and integration process in the metropolitan area. ⑤ In the past 20 years, the density of net carbon emissions in the Chongqing metropolitan area has increased as a whole, with the density of the core area increasing by 0.35 and the density of the core-edge area increasing by 0.34. By exploring the change and spatial correlation of land use carbon budget in the Chongqing metropolitan area, this study clarified the spatial distribution difference of carbon budget and provided support for regional green development.

5.
Int J Biol Macromol ; 279(Pt 3): 135223, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39241999

RESUMO

Laminaria digitata is a high-quality seaweed resource that is widely cultured and has good application prospects. In this study, Laminaria digitata fucoidan (LF) was extracted from Laminaria digitata, and purified using DEAE-Sepharose Fast Flow gel column to obtain four different grades. Among those, LF4 (Mw:165 kDa), mainly composed of fucose(56.80 %), had the highest total sugar (66.91 %) and sulfate (17.07 %) content. FT-RT and NMR results showed that LF4 was mainly composed of galactosylated galactofucose, and has a sulfate group attached to fucose C4. With the animal experimentation, it was revealed that hyperlipidaemic mice had significantly higher levels of TC (5.52 mmol/L), TG (2.28 mmol/L) and LDL-C (5.12 mmol/L) and significantly lower levels of HDL-C (2 mmol/L). However, LF had the efficacy in modulating the lipid metabolism disturbances induced by hyperlipidemia, as well as the ability to regulate cholesterol transport in serum. Moreover, it regulated AMPK/ACC, PPAR-α/LAXRa, Nrf2/Nqo1, TLR4/NF-κB signaling pathway genes and proteins expression in the liver. In addition, it promoted the production of beneficial short-chain fatty acids (SCFAs) while improving the composition and structure of gut microbiota, including balancing the abundance of Bacteroidota, Firmicutes, Muribaculaceae, Alloprevotella, Escherichia-Shigella, Prevotella and NK4A136. The results clearly indicated that LF4 could significantly ameliorate hyperlipidemia, suggesting its prospective application as a functional food.

6.
Front Microbiol ; 15: 1441398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220037

RESUMO

Studies in model microorganisms showed that cell division is highly vulnerable to high hydrostatic pressure (HHP). Disassembly of FtsZ filaments induced by HHP results in the failure of cell division and formation of filamentous cells in E. coli. The specific characteristics of FtsZ that allow for functional cell division in the deep-sea environments, especially in obligate piezophiles that grow exclusively under HHP condition, remain enigmatic. In this study, by using a self-developed HHP in-situ fixation apparatus, we investigated the effect of HHP on FtsZ by examining the subcellular localization of GFP-tagged FtsZ in vivo and the stability of FtsZ filament in vitro. We compared the pressure tolerance of FtsZ proteins from pressure-sensitive strain Shewanella oneidensis MR-1 (FtsZSo) and obligately piezophilic strain Shewanella benthica DB21MT-2 (FtsZSb). Our findings showed that, unlike FtsZSo, HHP hardly affected the Z-ring formation of FtsZSb, and filaments composed of FtsZSb were more stable after incubation under 50 MPa. By constructing chimeric and single amino acid mutated FtsZ proteins, we identified five residues in the N-terminal GTPase domain of FtsZSb whose mutation would impair the Z-ring formation under HHP conditions. Overall, these results demonstrate that FtsZ from the obligately piezophilic strain exhibits superior pressure tolerance than its homologue from shallow water species, both in vivo and in vitro. Differences in pressure tolerance of FtsZ are largely attributed to the N-terminal GTPase domain. This represents the first in-depth study of the adaptation of microbial cytoskeleton protein FtsZ to high hydrostatic pressure, which may provide insights into understanding the complex bioprocess of cell division under extreme environments.

7.
Front Nutr ; 11: 1292954, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144288

RESUMO

Background: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD. Methods: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Results: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.

9.
ACS Omega ; 9(31): 33702-33709, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39130592

RESUMO

Aiming at the problems of current similar hydrogel plugging agents, such as poor breaking performance, nonspontaneous degradation, and reservoir pollution which have been plaguing their application in temporary plugging operations, this study has synthesized a cross-linking agent for hydrogels with dimethylaminoethyl acrylate and dibromo-p-xylene as raw materials. With Fourier transform infrared, 1H nuclear magnetic resonance, and thermogravimetric analyses as representations of the structure and thermal stability of the cross-linking agent, a set of self-degrading hydrogel systems has been developed with the cross-linking agent as the core so as to make evaluations on the temperature resistance, plugging performance, and core damage performance of the hydrogel and conduct a study on its gelation kinetics. The research results show that the cross-linking agent shows good thermal stability. When applied in the hydrogel system, the hydrogel has shown high temperature resistance, maintaining gel strength for 5-10 days at 50-90 °C, with viscosity after complete degradation lower than 10 mPa·s. The excellent bearing strength of the hydrogel system has led to a core damage rate below 5%. The study on gelation kinetics of the hydrogel system shows that, with the increase in the concentration of the cross-linking agent, the gelation time of the hydrogel system is shortened, with the reaction order between the cross-linker concentration and the gelation time at about 0.6 under the condition of 50-90 °C.

10.
Cancer Immunol Immunother ; 73(10): 198, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105866

RESUMO

CD27 belongs to the tumor necrosis factor receptor superfamily and acts as a co-stimulatory molecule, modulating T and B cell responses. CD27 stimulation enhances T cell survival and effector functions, thus providing opportunities to develop therapeutic strategies. The current study aims to investigate the role of endogenous CD27 signaling in tumor growth and metastasis. CD8 + T cell-specific CD27 knockout (CD8Cre-CD27fl) mice were developed, while global CD27 knockout (KO) mice were also used in our studies. Flow cytometry analyses confirmed that CD27 was deleted specifically from CD8 + T cells without affecting CD4 + T cells, B cells, and HSPCs in the CD8Cre-CD27fl mice, while CD27 was deleted from all cell types in global CD27 KO mice. Tumor growth and metastasis studies were performed by injecting B16-F10 melanoma cells subcutaneously (right flank) or intravenously into the mice. We have found that global CD27 KO mice succumbed to significantly accelerated tumor growth compared to WT controls. In addition, global CD27 KO mice showed a significantly higher burden of metastatic tumor nests in the lungs compared to WT controls. However, there was no significant difference in tumor growth curves, survival, metastatic tumor nest counts between the CD8Cre-CD27fl mice and WT controls. These results suggest that endogenous CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in this commonly used melanoma model, presumably through stimulating antitumor activities of other types of immune cells.


Assuntos
Linfócitos T CD8-Positivos , Melanoma Experimental , Transdução de Sinais , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Animais , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Modelos Animais de Doenças , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Metástase Neoplásica , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
11.
J Cell Mol Med ; 28(12): e18483, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39051629

RESUMO

The development of high-throughput technologies has enhanced our understanding of small non-coding RNAs (sncRNAs) and their crucial roles in various diseases, including atrial fibrillation (AF). This study aimed to systematically delineate sncRNA profiles in AF patients. PANDORA-sequencing was used to examine the sncRNA profiles of atrial appendage tissues from AF and non-AF patients. Differentially expressed sncRNAs were identified using the R package DEGseq 2 with a fold change >2 and p < 0.05. The target genes of the differentially expressed sncRNAs were predicted using MiRanda and RNAhybrid. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. In AF patients, the most abundant sncRNAs were ribosomal RNA-derived small RNAs (rsRNAs), followed by transfer RNA-derived small RNAs (tsRNAs), and microRNAs (miRNAs). Compared with non-AF patients, 656 rsRNAs, 45 miRNAs, 191 tsRNAs and 51 small nucleolar RNAs (snoRNAs) were differentially expressed in AF patients, whereas no significantly differentially expressed piwi-interacting RNAs were identified. Two out of three tsRNAs were confirmed to be upregulated in AF patients by quantitative reverse transcriptase polymerase chain reaction, and higher plasma levels of tsRNA 5006c-LysCTT were associated with a 2.55-fold increased risk of all-cause death in AF patients (hazard ratio: 2.55; 95% confidence interval, 1.56-4.17; p < 0.001). Combined with our previous transcriptome sequencing results, 32 miRNA, 31 snoRNA, 110 nucleus-encoded tsRNA, and 33 mitochondria-encoded tsRNA target genes were dysregulated in AF patients. GO and KEGG analyses revealed enrichment of differentially expressed sncRNA target genes in AF-related pathways, including the 'calcium signaling pathway' and 'adrenergic signaling in cardiomyocytes.' The dysregulated sncRNA profiles in AF patients suggest their potential regulatory roles in AF pathogenesis. Further research is needed to investigate the specific mechanisms of sncRNAs in the development of AF and to explore potential biomarkers for AF treatment and prognosis.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Perfilação da Expressão Gênica , Pequeno RNA não Traduzido , Humanos , Fibrilação Atrial/genética , Pequeno RNA não Traduzido/genética , Apêndice Atrial/metabolismo , Masculino , Feminino , MicroRNAs/genética , Ontologia Genética , Idoso , Pessoa de Meia-Idade , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Regulação da Expressão Gênica , Transcriptoma/genética , Biologia Computacional/métodos , Prognóstico
12.
bioRxiv ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39005475

RESUMO

Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying this early dysregulation are not fully understood. Microglia, as the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. Here we investigated the role of microglia in the motor cortical circuits in a mouse model of TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording and longitudinal in vivo calcium imaging in awake mice, we observed neuronal hyperactivity at the initial stage of disease progression. Spatial and single-cell RNA sequencing revealed that microglia are the primary responders to motor cortical hyperactivity. We further identified a unique subpopulation of microglia, rod-shaped microglia, which are characterized by a distinct morphology and transcriptional profile. Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity. The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, exacerbated motor deficits, and further decreased survival rates of rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in the mouse model of TDP-43 related neurodegeneration.

13.
Brain ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001866

RESUMO

Mitochondrial and synaptic dysfunction are pathological features of brain aging and cognitive decline. Synaptic mitochondria are vital for meeting the high energy demands of synaptic transmission. However, little is known about the link between age-related metabolic changes and the integrity of synaptic mitochondria. To this end, we investigate the mechanisms of advanced glycation endproducts (AGEs)-mediated mitochondrial and synaptic stress and evaluate the strategies to eliminate these toxic metabolites. Using aged brain and novel transgenic mice overexpressing neuronal glyoxalase 1 (GLO1), we comprehensively analyzed alterations in accumulation/buildup of AGEs and related metabolites in synaptic mitochondria and the association of AGE levels with mitochondrial function. We demonstrate for the first time that synaptic mitochondria are an early and major target of AGEs and the related toxic metabolite methylglyoxal (MG), a precursor of AGEs. MG/AGEs-insulted synaptic mitochondria exhibit deterioration of mitochondrial and synaptic function. Such accumulation of MG/AGEs positively correlated with mitochondrial perturbation and oxidative stress in aging brain. Importantly, clearance of AGEs-related metabolites by enhancing neuronal GLO1, a key enzyme for detoxification/of AGEs, reduces synaptic mitochondrial AGEs accumulation and improves mitochondrial and cognitive function in aging and AGE-challenged mice. Furthermore, we evaluated the direct effect of AGEs on synaptic function in hippocampal neurons in live brain slices as an ex-vivo model and in vitro cultured hippocampal neurons by recording long-term potentiation (LTP) and measuring spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs). Neuronal GLO1 rescues deficits in AGEs-induced synaptic plasticity and transmission by fully recovery of decline in LTP or frequency of mEPSC. These studies explore crosstalk between synaptic mitochondrial dysfunction and age-related metabolic changes relevant to brain aging and cognitive decline. Synaptic mitochondria are particularly susceptible to AGEs-induced damage, highlighting the central importance of synaptic mitochondrial dysfunction in synaptic degeneration in age-related cognitive decline. Thus, augmenting GLO1 function to scavenge toxic metabolites represents a therapeutic approach to reduce age-related AGEs accumulation and to improve mitochondrial function and learning and memory.

14.
Open Med (Wars) ; 19(1): 20240983, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911257

RESUMO

The bleeding time and amount in the short-segment group were shorter than in the long-segment group, and the bleeding volume was less than in the long-segment group. The Japanese Orthopaedic Association low back pain score, Oswestry Dysfunction Index, and lumbar spine stiffness disability index score of the two groups were significantly improved preoperatively, postoperatively, and at 6 months, 1 year, and 2 years post-operation. The differences were statistically significant at different time points within the groups. Neurological function improved to varying degrees postoperatively. The Cobb angle was significantly higher in both groups (P < 0.05). Adjacent vertebral disease occurred in 10 of 64 patients with short-segment fixation, with a prevalence of 15.6%. Preoperative pelvic tilt angle, preoperative pelvic projection angle (PPA), preoperative degree of matching of PPA to LL (PI-LL), and preoperative coronal Cobb angle were higher in patients with adjacent vertebral disease. There were varying degrees of improvement in low back pain and spinal function after short-segment decompression and fusion internal fixation. However, the patients are generally elderly and at risk of persistent low back pain and accelerated degeneration of adjacent segments.

16.
Opt Express ; 32(11): 18618-18638, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859014

RESUMO

Fourier single pixel imaging utilizes pre-programmed patterns for laser spatial distribution modulation to reconstruct intensity image of the target through reconstruction algorithms. The approach features non-locality and high anti-interference performance. However, Poor image quality is induced when the target of interest is occluded in Fourier single pixel imaging. To address the problem, a deep learning-based image inpainting algorithm is employed within Fourier single pixel imaging to reconstruct partially obscured targets with high quality. It applies a distance-based segmentation method to segment obscured regions and the target of interest. Additionally, it utilizes an image inpainting network that combines multi-scale sparse convolution and transformer architecture, along with a reconstruction network that integrates Channel Attention Mechanism and Attention Gate modules to reconstruct complete and clear intensity images of the target of interest. The proposed method significantly expands the application scenarios and improves the imaging quality of Fourier single pixel imaging. Simulation and real-world experimental results demonstrate that the proposed method exhibits the high inpainting and reconstruction capacity in the conditions of hard occlusion and down-sampling.

17.
Biomed Pharmacother ; 177: 117006, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908197

RESUMO

Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4 mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1ß, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500 ng/mL) / adenosine triphosphate (5 mM) and treated it with GB (10, 20, and 40 µM). GB upregulated the expression of mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of reactive oxygen species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1ß, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5 mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy.


Assuntos
Ginkgolídeos , Inflamassomos , Lactonas , Microglia , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neuralgia , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ginkgolídeos/farmacologia , Ginkgolídeos/uso terapêutico , Mitofagia/efeitos dos fármacos , Lactonas/farmacologia , Lactonas/uso terapêutico , Inflamassomos/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Masculino , Ratos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo
18.
Bioresour Technol ; 402: 130844, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754560

RESUMO

In this study, a novel magnetic Ni-Fe2O3-C catalyst combined with electromagnetic induction heating in biomass steam gasification was proposed to enhance H2 production. Better catalytic performance for H2 production was observed with the Ni-Fe2O3-C catalyst under induction heating, resulting in an increase in H2 yield from 735.1 to 2271.2 mL/g-biomass (a 209.1 % enhancement). SEM, TGA and XRD analysis demonstrated a significant decrease in coking deposition, caking, and particle agglomeration of the Ni-Fe2O3-C catalyst under induction heating, while maintaining more active sites. Importantly, the benefits of induction heating were also applicable to different magnetic catalysts like Ni-Al2O3-C, Ni-ZrO2-C, and Ni-MgO-C. Experimental results revealed a logarithmic correlation between the increase in H2 yields due to induction heating and the magnetic saturation (Ms) of the catalysts. The Ni-Fe2O3-C catalyst, with a high Ms of 50.9 emu/g, showed the highest catalytic activity for H2 production under induction heating in this study.


Assuntos
Biomassa , Compostos Férricos , Hidrogênio , Níquel , Vapor , Catálise , Hidrogênio/química , Níquel/química , Compostos Férricos/química , Temperatura Alta , Calefação , Difração de Raios X , Fenômenos Eletromagnéticos
19.
Sci Immunol ; 9(95): eadj9730, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728414

RESUMO

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.


Assuntos
Autoimunidade , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoimunidade/imunologia , Sistema Nervoso Central/imunologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Receptores de Antígenos Quiméricos/imunologia , Análise de Célula Única
20.
Perfusion ; : 2676591241252721, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703049

RESUMO

INTRODUCTION: Axillary artery cannulation (AAC) has been widely employed in total arch replacement surgeries using the frozen elephant trunk (FET) technique for acute type A aortic dissection (ATAAD), showing better clinical results than femoral artery cannulation (FAC). Nevertheless, in type II hybrid arch repair (HAR), FAC is crucial for lower body perfusion. Hence, it is unclear whether AAC remains necessary or if AAC represents a more advantageous method for initiating cardiopulmonary bypass. METHODS: We conducted a study involving patients diagnosed with ATAAD who underwent type II HAR from August 2021 to December 2022. Demographic baseline and intraoperative data were collected, and the postoperative outcomes of patients receiving FAC only were compared with those receiving AAC. RESULTS: There were no significant differences in baseline demographics between patients who underwent FAC alone (n = 46) and those who underwent AAC (n = 39). Patients who underwent AAC showed a lower incidence of transient neurological dysfunction (TND) post-surgery compared to those who underwent FAC (12.8% vs 32.6%, p = .032). There were no significant differences between the groups in terms of postoperative mortality within 30 days, permanent neurological dysfunction (PND), length of stay in the intensive care unit (ICU) and postoperative ward, duration of mechanical ventilation, and other complications. CONCLUSIONS: Axillary artery cannulation may decrease the incidence of postoperative transient neurological dysfunction (TND) in type II HAR for ATAAD. Nonetheless, studies with larger sample sizes are necessary.

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