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1.
PLoS One ; 19(4): e0301666, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564570

RESUMO

PURPOSE: This study aimed to investigate the mediating role of fear of progression on illness perception and social alienation among maintenance hemodialysis (MHD) patients. BACKGROUND: MHD is frequently accompanied by increased pain and complications such as itchy skin, chronic fatigue, and muscle spasms. Cardiovascular disease rates are also elevated among MHD patients, which can heighten their anxiety regarding prognosis and treatment discomfort. This chronic fear may severely impact social functioning, leading patients to withdraw from interpersonal interactions and experience heightened helplessness and loneliness. Further investigation is necessary to understand the factors behind the high level of social alienation in MHD patients and their underlying mechanisms. DESIGN: A cross-sectional study guided by the STROBE. METHODS: A convenience sample of 230 MHD patients were enrolled from January to May 2023. Data including demographic and clinical characteristics, illness perception, fear of progression, and social alienation were collected. Descriptive analysis and Pearson correlations were conducted using IBM SPSS version 25.0. The mediating effect was analyzed using Model 4 of the PROCESS macro for SPSS, with the Bootstrap method employed to assess its significance. RESULTS: The score of social alienation in MHD patients was high, with illness perception and fear of progression both significantly correlated with social alienation. In the mediating effects model, illness perception can predict social alienation in MHD patients, and fear of progression use plays a part in mediating the process by which illness perception affects social alienation. The Kappa Squared (κ2) value of 21.9%, suggests a medium effect size. CONCLUSIONS: Illness perception directly predicts social alienation in MHD patients and exerts an indirect effect through the mediating role of fear of progression. Suggests that healthcare professionals should concentrate on MHD patients with high negative illness perceptions to alleviate their fear of progression, thereby decreasing the level of social alienation and enhancing their integration into society.


Assuntos
Diálise Renal , Alienação Social , Humanos , Estudos Transversais , Medo , Percepção
2.
BMC Genomics ; 25(1): 384, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637729

RESUMO

BACKGROUND: Curcubita ficifolia Bouché (Cucurbitaceae) has high value as a food crop and medicinal plant, and also has horticultural value as rootstock for other melon species. China is home to many different cultivars, but the genetic diversity of these resources and the evolutionary relationships among them, as well as the differences between C. ficifolia and other Cucurbita species, remain unclear. RESULTS: We investigated the chloroplast (cp) genomes of 160 C. ficifolia individuals from 31 populations in Yunnan, a major C. ficifolia production area in China. We found that the cp genome of C. ficifolia is ~151 kb and contains 128 genes, of which 86 are protein coding genes, 34 encode tRNA, and eight encode rRNAs. We also identified 64 SSRs, mainly AT repeats. The cp genome was found to contain a total of 204 SNP and 57 indels, and a total of 21 haplotypes were found in the 160 study individuals. The reverse repeat (IR) region of C. ficifolia contained a few differences compared with this region in the six other Cucurbita species. Sequence difference analysis demonstrated that most of the variable regions were concentrated in the single copy (SC) region. Moreover, the sequences of the coding regions were found to be more similar among species than those of the non-coding regions. The phylogenies reconstructed from the cp genomes of 61 representative species of Cucurbitaceae reflected the currently accepted classification, in which C. ficifolia is sister to the other Cucurbita species, however, different interspecific relationships were found between Cucurbita species. CONCLUSIONS: These results will be valuable in the classification of C. ficifolia genetic resources and will contribute to our understanding of evolutionary relationships within the genus Cucurbita.


Assuntos
Cucurbita , Cucurbitaceae , Genoma de Cloroplastos , Humanos , Cucurbita/genética , Cucurbitaceae/genética , Filogenia , China , Cloroplastos/genética , Variação Genética
3.
J Neurotrauma ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517097

RESUMO

The potential influence of pituitary-related hormones (including both pituitary gland and target gland hormones) on functional recovery after traumatic brain injury has been observed. However, the relationship between these hormones and the recovery of consciousness in patients with disorders of consciousness (DOC) remains unclear. In this retrospective and observational study, 208 patients with DOC were recruited. According to the Glasgow Outcome Scale (GOS) scores after 6 months, DOC patients were categorized into two subgroups: a favorable prognosis subgroup (n = 38) comprising those who regained consciousness (GOS ≥ 3), and a poor prognosis subgroup (n = 156) comprising those who remained in DOC (GOS < 3). Comparative analyses of pituitary-related hormone levels between the two subgroups were conducted. Furthermore, a binary logistic regression analysis was conducted to assess the predictive value of pituitary-related hormones for the patients' prognosis. The favorable prognosis subgroup showed a significant increase in Adrenocorticotropic hormone (ACTH) levels (p = 0.036). Moreover, higher ACTH levels and shorter days since injury were significantly associated with a better prognosis, with odds ratios of 0.928 (95% CI = 0.873-0.985, p = 0.014) and 1.015 (95% CI = 1.005-1.026, p = 0.005), respectively. A subsequent receiver operating characteristic analysis demonstrated the potential to predict patients' prognosis with an area under the curve value of 0.78, an overall accuracy of 75.5%, a sensitivity of 77.5%, and a specificity of 66.7%. Our findings indicate that ACTH levels could serve as a clinically valuable and convenient predictor for patients' prognosis.

4.
Neuroimage ; 290: 120580, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508294

RESUMO

Diagnosis of disorders of consciousness (DOC) remains a formidable challenge. Deep learning methods have been widely applied in general neurological and psychiatry disorders, while limited in DOC domain. Considering the successful use of resting-state functional MRI (rs-fMRI) for evaluating patients with DOC, this study seeks to explore the conjunction of deep learning techniques and rs-fMRI in precisely detecting awareness in DOC. We initiated our research with a benchmark dataset comprising 140 participants, including 76 unresponsive wakefulness syndrome (UWS), 25 minimally conscious state (MCS), and 39 Controls, from three independent sites. We developed a cascade 3D EfficientNet-B3-based deep learning framework tailored for discriminating MCS from UWS patients, referred to as "DeepDOC", and compared its performance against five state-of-the-art machine learning models. We also included an independent dataset consists of 11 DOC patients to test whether our model could identify patients with cognitive motor dissociation (CMD), in which DOC patients were behaviorally diagnosed unconscious but could be detected conscious by brain computer interface (BCI) method. Our results demonstrate that DeepDOC outperforms the five machine learning models, achieving an area under curve (AUC) value of 0.927 and accuracy of 0.861 for distinguishing MCS from UWS patients. More importantly, DeepDOC excels in CMD identification, achieving an AUC of 1 and accuracy of 0.909. Using gradient-weighted class activation mapping algorithm, we found that the posterior cortex, encompassing the visual cortex, posterior middle temporal gyrus, posterior cingulate cortex, precuneus, and cerebellum, as making a more substantial contribution to classification compared to other brain regions. This research offers a convenient and accurate method for detecting covert awareness in patients with MCS and CMD using rs-fMRI data.


Assuntos
Transtornos da Consciência , Aprendizado Profundo , Humanos , Encéfalo/diagnóstico por imagem , Estado Vegetativo Persistente , Inconsciência , Estado de Consciência
5.
Am J Pathol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548269

RESUMO

Two major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1), are implicated in exfoliation glaucoma, yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, the pan-LOX inhibitor ß-aminopropionitrile (BAPN) was used to treat adult wild-type (WT) and Fbn1C1041G/+ mice for 8 weeks and their eyes were examined. Although intraocular pressure did not change and exfoliation material was not detected in the eyes, BAPN treatment worsened optic nerve and axon expansion in Fbn1C1041G/+ mice, an early sign of axonal damage in rodent models of glaucoma. Disruption of elastic fibers was detected only in Fbn1C1041G/+ mice, which increased with BAPN treatment, as shown by histologic and immunohistochemical staining of the optic nerve pia mater. Transmission electron microscopy showed that Fbn1C1041G/+ mice had fewer microfibrils, smaller elastin cores, and a lower density of elastic fibers compared with WT mice in control groups. BAPN treatment led to elastin core expansion in both WT and Fbn1C1041G/+ mice, but an increase in the density of elastic fiber was confined to Fbn1C1041G/+ mice. LOX inhibition had a stronger effect on optic nerve and elastic fiber parameters in the context of Fbn1 mutation, indicating the Marfan mouse model with LOX inhibition warrants further investigation for exfoliation glaucoma pathogenesis.

6.
Mutagenesis ; 39(3): 181-195, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38468450

RESUMO

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.


Assuntos
Aflatoxina B1 , Fumonisinas , Hepatócitos , Fumonisinas/toxicidade , Humanos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Aflatoxina B1/toxicidade , Linhagem Celular , Inflamação/genética , Inflamação/induzido quimicamente , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo
7.
Math Biosci Eng ; 21(2): 1844-1856, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38454663

RESUMO

Liver rupture repair surgery serves as one tool to treat liver rupture, especially beneficial for cases of mild liver rupture hemorrhage. Liver rupture can catalyze critical conditions such as hemorrhage and shock. Surgical workflow recognition in liver rupture repair surgery videos presents a significant task aimed at reducing surgical mistakes and enhancing the quality of surgeries conducted by surgeons. A liver rupture repair simulation surgical dataset is proposed in this paper which consists of 45 videos collaboratively completed by nine surgeons. Furthermore, an end-to-end SA-RLNet, a self attention-based recurrent convolutional neural network, is introduced in this paper. The self-attention mechanism is used to automatically identify the importance of input features in various instances and associate the relationships between input features. The accuracy of the surgical phase classification of the SA-RLNet approach is 90.6%. The present study demonstrates that the SA-RLNet approach shows strong generalization capabilities on the dataset. SA-RLNet has proved to be advantageous in capturing subtle variations between surgical phases. The application of surgical workflow recognition has promising feasibility in liver rupture repair surgery.


Assuntos
Fígado , Redes Neurais de Computação , Humanos , Fluxo de Trabalho , Simulação por Computador , Fígado/cirurgia , Hemorragia/cirurgia
8.
Synth Syst Biotechnol ; 9(1): 134-143, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38318491

RESUMO

The biosynthesis of bioactive secondary metabolites, specifically antibiotics, is of great scientific and economic importance. The control of antibiotic production typically involves different processes and molecular mechanism. Despite numerous efforts to improve antibiotic yields, joint engineering strategies for combining genetic manipulation with fermentation optimization remain finite. Lincomycin A (Lin-A), a lincosamide antibiotic, is industrially fermented by Streptomyces lincolnensis. Herein, the leucine-responsive regulatory protein (Lrp)-type regulator SLCG_4846 was confirmed to directly inhibit the lincomycin biosynthesis, whereas indirectly controlled the transcription of SLCG_2919, the first reported repressor in S. lincolnensis. Inactivation of SLCG_4846 in the high-yield S. lincolnensis LA219X (LA219XΔ4846) increases the Lin-A production and deletion of SLCG_2919 in LA219XΔ4846 exhibits superimposed yield increment. Given the effect of the double deletion on cellular primary metabolism of S. lincolnensis, Plackett-Burman design, steepest ascent and response surface methodologies were utilized and employed to optimize the seed medium of this double mutant in shake flask, and Lin-A yield using optimal seed medium was significantly increased over the control. Above strategies were performed in a 15-L fermenter. The maximal yield of Lin-A in LA219XΔ4846-2919 reached 6.56 g/L at 216 h, 55.1 % higher than that in LA219X at the parental cultivation (4.23 g/L). This study not only showcases the potential of this strategy to boost lincomycin production, but also could empower the development of high-performance actinomycetes for other antibiotics.

9.
Mar Pollut Bull ; 199: 116044, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237250

RESUMO

Using appropriate zooplankton to transfer the primary productivity of harmful algae to higher trophic levels through food chain is an eco-friendly mode to remove harmful algae. To assess the top-down efficiency of rotifer removing Phaeocystis and the salinity effect, we adopted a series of salinities to carry out Phaeocystis-rotifer population dynamics and rotifer life-history experiments. Results showed that the time for rotifers to remove Phaeocystis population was the shortest when the salinity was ≤20 ‰. With salinity rising to above 25 ‰, although the clearance time of Phaeocystis population by rotifer was significantly prolonged, ultimately the Phaeocystis population were almost completely eliminated at all salinities. Additionally, rotifer matured and reproduced earlier at low salinity, while high salinity significantly delayed first reproductive time and decreased the total offspring. The above findings are helpful to assess the impacts of external environmental factors on the application of zooplankton to control harmful algae.


Assuntos
Haptófitas , Rotíferos , Animais , Salinidade , Dinâmica Populacional , Reprodução
10.
Cell Commun Signal ; 22(1): 33, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217003

RESUMO

BACKGROUND: Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H2S) exerts a neuroprotective effect in many neurodegenerative diseases. However, whether H2S is anti-PANoptosis and neuroprotective in the progression of acute SCIRI remains unclear. Thus, in this study we aimed to explore the role of H2S in SCIRI and its underlying mechanisms. METHODS: Measurements of lower limb function, neuronal activity, microglia/macrophage function histopathological examinations, and biochemical levels were performed to examine the efficacy of H2S and to further demonstrate the mechanism and treatment of SCIRI. RESULTS: The results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score. Additionally, the number of TUNEL-positive and cleaved caspase-3-positive cells was decreased, and the upregulation of expression of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 expression were reversed after GYY4137 administration. Meanwhile, both the expression and activation of p-MLKL, p-RIP1, and p-RIP3, along with the number of PI-positive and RIP3-positive neurons, were decreased in GYY4137-treated rats. Furthermore, GYY4137 administration reduced the expression of NLRP3, cleaved caspase-1 and cleaved GSDMD, decreased the colocalization NeuN/NLRP3 and Iba1/interleukin-1ß-expressing cells, and inhibited proinflammatory factors and microglia/macrophage polarization. CONCLUSIONS: H2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.


Assuntos
Sulfeto de Hidrogênio , Morfolinas , Fármacos Neuroprotetores , Compostos Organotiofosforados , Traumatismo por Reperfusão , Ratos , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 3/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/metabolismo , Medula Espinal/patologia , Apoptose , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-38244151

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUT) are primarily causal for end-stage renal disease and have significant implications for long-term survival. A total of 39 healthy controls and 94 children with chronic kidney disease (CKD) were enrolled (3-12 years old as children, 13-18 years old as adolescents), who were divided into CAKUT and Non-CAKUT according to the etiology of CKD. CKD group was further classified according to estimating glomerular filtration rate (eGFR). Circulating levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemokine-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were analyzed. The relationship between these inflammatory markers with eGFR and the kidney injury parameter (urine protein) was investigated to assess their potential as early markers of disease progression. All circulating levels of these inflammatory cytokines were increased in CKD patients (including CAKUT and Non-CAKUT) compared with healthy subjects. The circulating levels of MCP-1 and TGF-ß1 were increased in CAKUT adolescents compared with CAKUT children. In CAKUT children, levels of MCP-1 and TGF-ß1 increased as CKD progressed, and MCP-1 and TGF-ß1 were negatively and significantly correlated with eGFR and positively with urine protein. MCP-1 and TGF-ß1 may contribute to the early detection of CKD and disease stage/progression in CAKUT children.

12.
Oncol Rep ; 51(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38186298

RESUMO

Osteosarcomas are malignant bone tumors that typically originate in the epiphyses of the long bones of the extremities in adolescents. Asiatic acid has been reported to possess anti­inflammatory, neuroprotective, antidiabetic, antitumor and antimicrobial activities. The present study used a combination of network pharmacological prediction and in vitro experimental validation to explore the potential pharmacological mechanism of asiatic acid against osteosarcoma. A total of 78 potential asiatic acid targets in osteosarcoma were identified using databases. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/AKT and MAPK signaling pathways are essential in the treatment of osteosarcoma with asiatic acid. Molecular docking revealed binding of asiatic acid to EGFR, Caspase­3, ESR1, HSP90AA1, IL­6 and SRC proteins. asiatic acid inhibited proliferation through G2/M cell cycle arrest in osteosarcoma cells. In addition, asiatic acid induced mitochondria­dependent apoptosis as demonstrated by increases in Bax and VDAC1 expression, and a decrease in Bcl­2 protein expression. The increased autophagosomes, increased LC3­II/I ratios and decreased p62 expression in the treatment group indicated that asiatic acid triggered autophagy. In addition, asiatic acid decreased the levels of phosphorylated (p­)PI3K/PI3K and p­AKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of p­ERK1/2/ERK1/2, p­p38/p38 and p­JNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Adolescente , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico
13.
Aging (Albany NY) ; 16(1): 153-168, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38175691

RESUMO

BACKGROUND: Osteoarthritis (OA) is one of the main causes of pain and disability in the world, it may be caused by many factors. Aging plays a significant role in the onset and progression of OA. However, the mechanisms underlying it remain unknown. Our research aimed to uncover the role of aging-related genes in the progression of OA. METHODS: In Human OA datasets and aging-related genes were obtained from the GEO database and the HAGR website, respectively. Bioinformatics methods including Gene Ontology (GO), Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment, and Protein-protein interaction (PPI) network analysis were used to analyze differentially expressed aging-related genes (DEARGs) in the normal control group and the OA group. And then weighted gene coexpression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO) regression, and the Random Forest (RF) machine learning algorithms were used to find the hub genes. RESULTS: Four overlapping hub genes: HMGB2, CDKN1A, JUN, and DDIT3 were identified. According to the nomogram model and receiver operating characteristic (ROC) curve analysis, four hub DEARGs had good diagnostic value in distinguishing normal from OA. Furthermore, the qRT-PCR test demonstrated that HMGB2, CDKN1A, JUN, and DDIT3 mRNA expression levels were lower in OA group than in normal group. CONCLUSION: Finally, these four-hub aging-related genes may help us understand the underlying mechanism of aging in osteoarthritis and could be used as possible diagnostic and therapeutic targets.


Assuntos
Proteína HMGB2 , Osteoartrite , Humanos , Biologia Computacional , Aprendizado de Máquina , Osteoartrite/diagnóstico , Osteoartrite/genética , Envelhecimento/genética
14.
ACS Appl Mater Interfaces ; 16(3): 4071-4088, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38194589

RESUMO

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.


Assuntos
Dendrímeros , Neoplasias , Animais , Camundongos , Hidrogéis/química , Micelas , Dendrímeros/farmacologia , Dendrímeros/uso terapêutico , Neoplasias/tratamento farmacológico , Doxorrubicina/química , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral
15.
Brain Res ; 1823: 148680, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977412

RESUMO

This study aimed to investigate whether brain anatomical structures and functional network connectivity are altered after chronic complete thoracic spinal cord injury (cctSCI) and to determine how these changes impact clinical outcomes. Structural and resting-state functional MRI was performed for 19 cctSCI patients (18 for final statistics) and 19 healthy controls. Voxel-based morphometry (VBM) was used to assess gray matter volume (GMV) with differences between cctSCI patients and controls. VBM results were used as seeds for whole-brain functional connectivity (FC) analysis. The relationship between brain changes and clinical variables was investigated. Compared with those of the control group, the left triangular inferior frontal gyrus, middle frontal gyrus, orbital inferior frontal gyrus, precuneus and parietal superior gyrus volumes of SCI patients decreased, while the left superior frontal gyrus and supplementary motor area volumes increased. Additionally, when the regions with increased GMV were used as seeds, the FC of the parahippocampus and thalamus increased. Subsequent partial correlation analysis showed a positive correlation between FC and total sensorimotor score based on the ASIA criteria (p = 0.001, r = 0.746). Overall, the structural and functional changes in the brain after cctSCI occurred in some visual and cognitive areas and sensory or motor control areas. These findings aid in improving our understanding of the underlying brain injury mechanisms and the subsequent structural and functional reorganization to reveal potential therapeutic targets and track treatment outcomes.


Assuntos
Encéfalo , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/diagnóstico por imagem , Substância Cinzenta , Córtex Cerebral , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos
16.
Adv Biol (Weinh) ; 8(1): e2300424, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37786299

RESUMO

Paraplegia is a serious consequence of spinal cord ischemia-reperfusion (SCIR) injury, which leads to neuron death and permanent loss of motor function. However, there is no effective treatment for SCIR. Melatonin exerts a neuroprotective effect in neurodegenerative diseases. However, whether pyroptosis, apoptosis, and necroptosis (PANoptosis) is the primary cause of the massive neural death in SCIR is unknown, and if melatonin exhibits anti-PANoptotic effect in rescuing the disastrous damage is to be decided. This study indicates that melatonin confers neuroprotection in SCIR, attenuating the loss of Nissl body and improving Basso, Beattie & Bresnahan locomotor rating scale scores. Specifically, the apoptotic hallmarks in neurons are increased in SCIR injured spinal cord compared to the sham group. The upregulated trend is reversed by melatonin while the effect of melatonin is abolished by the administration of luzindole, a selective melatonin receptor antagonist. Moreover, similar patterns are found in the necroptotic markers in neurons, the pyroptotic indicators, and the interleukin-1ß staining in microglia. In conclusion, PANoptosis may underlie the mass neural death and paraplegia in SCIR, and melatonin confers neuroprotection to the spinal cord via inhibiting PANoptosis.


Assuntos
Melatonina , Traumatismo por Reperfusão , Isquemia do Cordão Espinal , Ratos , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Ratos Sprague-Dawley , Isquemia do Cordão Espinal/tratamento farmacológico , Paraplegia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Reperfusão
17.
J Basic Microbiol ; 64(1): 119-127, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37562983

RESUMO

The transcription factor (TF)-mediated regulatory network controlling lincomycin production in Streptomyces lincolnensis is yet to be fully elucidated despite several types of associated TFs having been reported. SLCG_2919, a tetracycline repressor (TetR)-type regulator, was the first TF to be characterized outside the lincomycin biosynthetic cluster to directly suppress the lincomycin biosynthesis in S. lincolnensis. In this study, improved genomic systematic evolution of ligands by exponential enrichment (gSELEX), an in vitro technique, was adopted to capture additional SLCG_2919-targeted sequences harboring the promoter regions of SLCG_6675, SLCG_4123-4124, SLCG_6579, and SLCG_0139-0140. The four DNA fragments were confirmed by electrophoretic mobility shift assays (EMSAs). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) showed that the corresponding target genes SLCG_6675 (anthranilate synthase), SLCG_0139 (LysR family transcriptional regulator), SLCG_0140 (beta-lactamase), SLCG_6579 (cytochrome P450), SLCG_4123 (bifunctional DNA primase/polymerase), and SLCG_4124 (magnesium or magnesium-dependent protein phosphatase) in ΔSLCGL_2919 were differentially increased by 3.3-, 4.2-, 3.2-, 2.5-, 4.6-, and 2.2-fold relative to those in the parental strain S. lincolnensis LCGL. Furthermore, the individual inactivation of these target genes in LCGL reduced the lincomycin yield to varying degrees. This investigation expands on the known DNA targets of SLCG_2919 to control lincomycin production and lays the foundation for improving industrial lincomycin yields via genetic engineering of this regulatory network.


Assuntos
Proteínas de Bactérias , Magnésio , Streptomyces , Magnésio/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos , Lincomicina , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tetraciclina , DNA , Regulação Bacteriana da Expressão Gênica
18.
Neural Netw ; 171: 332-342, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38113718

RESUMO

The 6-Degree-of-Freedom (6-DoF) robotic grasping is a fundamental task in robot manipulation, aimed at detecting graspable points and corresponding parameters in a 3D space, i.e affordance learning, and then a robot executes grasp actions with the detected affordances. Existing research works on affordance learning predominantly focus on learning local features directly for each grid in a voxel scene or each point in a point cloud scene, subsequently filtering the most promising candidate for execution. Contrarily, cognitive models of grasping highlight the significance of global descriptors, such as size, shape, and orientation, in grasping. These global descriptors indicate a grasp path closely tied to actions. Inspired by this, we propose a novel bio-inspired neural network that explicitly incorporates global feature encoding. In particular, our method utilizes a Truncated Signed Distance Function (TSDF) as input, and employs the recently proposed Transformer model to encode the global features of a scene directly. With the effective global representation, we then use deconvolution modules to decode multiple local features to generate graspable candidates. In addition, to integrate global and local features, we propose using a skip-connection module to merge lower-layer global features with higher-layer local features. Our approach, when tested on a recently proposed pile and packed grasping dataset for a decluttering task, surpassed state-of-the-art local feature learning methods by approximately 5% in terms of success and declutter rates. We also evaluated its running time and generalization ability, further demonstrating its superiority. We deployed our model on a Franka Panda robot arm, with real-world results aligning well with simulation data. This underscores our approach's effectiveness for generalization and real-world applications.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Aprendizagem , Generalização Psicológica , Simulação por Computador
19.
Cell Rep ; 43(1): 113633, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38159279

RESUMO

Arousal and awareness are two components of consciousness whose neural mechanisms remain unclear. Spontaneous peaks of global (brain-wide) blood-oxygenation-level-dependent (BOLD) signal have been found to be sensitive to changes in arousal. By contrasting BOLD signals at different arousal levels, we find decreased activation of the ventral posterolateral nucleus (VPL) during transient peaks in the global signal in low arousal and awareness states (non-rapid eye movement sleep and anesthesia) compared to wakefulness and in eyes-closed compared to eyes-open conditions in healthy awake individuals. Intriguingly, VPL-global co-activation remains high in patients with unresponsive wakefulness syndrome (UWS), who exhibit high arousal without awareness, while it reduces in rapid eye movement sleep, a state characterized by low arousal but high awareness. Furthermore, lower co-activation is found in individuals during N3 sleep compared to patients with UWS. These results demonstrate that co-activation of VPL and global activity is critical to arousal but not to awareness.


Assuntos
Sono , Núcleos Ventrais do Tálamo , Humanos , Sono/fisiologia , Nível de Alerta/fisiologia , Vigília/fisiologia , Encéfalo/fisiologia , Eletroencefalografia
20.
Appl Opt ; 62(34): 9028-9035, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38108738

RESUMO

The terahertz (THz) wave contains abundant spectrum resources and is still in the early stages of development. It has great application potential in biomedical engineering and public security. However, in these areas there are difficulties to overcome like measuring the wide band absorption of a trace mount sample. In this paper, a THz absorption enhancing method is suggested by a multiplexing strategy. By gradually expanding the stretchable substrate of the dielectric metagrating with an oblique THz wave incidence, the resonance peak frequencies can cover the frequency range of 0.48-0.58 THz. Also, the corresponding envelope built by the peaks of the metagrating absorption spectrum with the 0.2 µm α-lactose film can demonstrate 71.55 times boosting compared to the original absorption amplitude of the film. The investigation witnesses possibilities for the detection of biomacromolecular materials.

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