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In contemporary literature, little attention has been paid to the association between coronavirus disease-2019 (COVID-19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID-19 exposures (critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 33 different types of cancers of the European population. The results of the inverse-variance-weighted model indicated that genetic liabilities to critically ill COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (odds ratio [OR] = 1.0924; p-value = 0.0116), esophageal cancer (OR = 1.0004; p-value = 0.0226), colorectal cancer (OR = 1.0010; p-value = 0.0242), stomach cancer (OR = 1.2394; p-value = 0.0331), and colon cancer (OR = 1.0006; p-value = 0.0453). The genetic liabilities to hospitalized COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (OR = 1.1096; p-value = 0.0458), esophageal cancer (OR = 1.0005; p-value = 0.0440) as well as stomach cancer (OR = 1.3043; p-value = 0.0476). The genetic liabilities to SARS-CoV-2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p-value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p-value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID-19 had causal effects on cancer risk.
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Neoplasias da Mama , COVID-19 , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Feminino , SARS-CoV-2 , Estado Terminal , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery. METHODS: In this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery. RESULTS: Lung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation. CONCLUSIONS: During general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn .
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Laparoscopia , Atelectasia Pulmonar , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pulmão/diagnóstico por imagem , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
Fifteen new and rare iridoid glucoside dimers, cornusides A-O (1-15), and 10 known iridoid glucosides (16-25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1-25 were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23 showed inhibitory effects, with IC50 values of 11.9, 12.2, 14.0, 7.0, and 6.9 µM, respectively.
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Cornus/química , Frutas/química , Glucosídeos/química , Glucosídeos Iridoides/química , Iridoides/química , Piranos/química , Extratos Vegetais/químicaRESUMO
Immunogenic antigen (jujuboside A-BSA) and coating antigen (jujuboside A-OVA) of jujuboside A were synthesized by sodium periodate oxidation method for the first time. Jujuboside A artificial antigen was confirmed by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS). The titer and specificity of the antibody in serum of immunized mice were detected by enzyme-linked immunosorbent assay (ELISA). The corrected relation curve of inhibition rate showed that the antibody against Jujuboside A obtained from immunized mice could bind to jujuboside A and the titer was up to 1â¶4 000. The jujuboside A artificial antigen was synthesized, which can be used further to preparation of monoclonal antibody and the pharmacokinetics study of jujuboside A in laboratory animals.
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Antígenos/química , Saponinas/síntese química , Animais , Ensaio de Imunoadsorção Enzimática , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
To investigate the chemical compounds from the fruit of Cornus officinalis, six compounds were isolated and determined by extensive spectroscopic analysis as 6'-O-acetyl-7α-O-ethyl morroniside (1), (-)-isolariciresinol 3α-O-ß-D-glucopyranoside(2), apigenin (3), cirsiumaldehyde(4), p-coumaric acid (5), caffeic acid (6). Compound 1 was a new iridoid glucoside,and compounds 2-4 were obtained from the Cornus genus for the first time. Compounds 2-6 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation. The MTT results showed that compound 4 increased cell viability moderately in OGD/R treated PC12 cells at the concentration of 1.0 µmolâ¢L⻹.
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Cornus/química , Frutas/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Animais , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Células PC12 , Compostos Fitoquímicos/química , RatosRESUMO
Retinal vessel segmentation plays a vital role in the clinical diagnosis of ophthalmic diseases. Despite convolutional neural networks (CNNs) excelling in this task, challenges persist, such as restricted receptive fields and information loss from downsampling. To address these issues, we propose a new multi-fusion network with grouped attention (MAG-Net). First, we introduce a hybrid convolutional fusion module instead of the original encoding block to learn more feature information by expanding the receptive field. Additionally, the grouped attention enhancement module uses high-level features to guide low-level features and facilitates detailed information transmission through skip connections. Finally, the multi-scale feature fusion module aggregates features at different scales, effectively reducing information loss during decoder upsampling. To evaluate the performance of the MAG-Net, we conducted experiments on three widely used retinal datasets: DRIVE, CHASE and STARE. The results demonstrate remarkable segmentation accuracy, specificity and Dice coefficients. Specifically, the MAG-Net achieved segmentation accuracy values of 0.9708, 0.9773 and 0.9743, specificity values of 0.9836, 0.9875 and 0.9906 and Dice coefficients of 0.8576, 0.8069 and 0.8228, respectively. The experimental results demonstrate that our method outperforms existing segmentation methods exhibiting superior performance and segmentation outcomes.
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Aprendizagem , Vasos Retinianos , Vasos Retinianos/diagnóstico por imagem , Redes Neurais de Computação , Processamento de Imagem Assistida por ComputadorRESUMO
The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.
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Biomimética , Células Epidérmicas , Epiderme/patologia , Queratinócitos , Pele , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
The dermal-epidermal junction (DEJ), located between the dermal-epidermal layers in human skin tissue, plays a significant role in its function. However, the limitations of biomaterial properties and microstructure fabrication methods mean that most current tissue engineered skin models do not consider the existence of DEJ. In this study, a nanofiber membrane that simulates the fluctuating structure of skin DEJ was prepared by the composite molding process. Electrospinning is a technique for the production of nanofibers, which can customize the physical and biological properties of biomaterials. At present, electrospinning technology is widely used in the simulation of customized natural skin DEJ. In this study, four different concentration ratios of poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanofiber membranes were prepared based on electrospinning technology. We selected a 15%PLGA + 5%PCL nanofiber membrane with mechanical properties, dimensional stability, hydrophilicity, and biocompatibility after physical properties and biological characterization. Then, the array-based microstructure model was prepared by three-dimensional (3D) printing. Subsequently, the microstructure was created on a 15%PLGA + 5%PCL membrane by the micro-imprinting process. Finally, the cell proliferation and live/dead tests of keratinocytes (HaCaTs) and fibroblasts (HSFs) were measured on the microstructural membrane and flat membrane. The results showed that 15%PLGA + 5%PCL microstructure membrane was more beneficial to promote the adhesion and proliferation of HaCaTs and HSFs than a flat membrane.
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Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.
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Polivinil , Engenharia Tecidual , Alicerces Teciduais , Polivinil/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Humanos , Impressão Tridimensional , Materiais Biocompatíveis/química , Polímeros/química , Animais , Polímeros de FluorcarbonetoRESUMO
Objective: This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM. Methods: Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2. Results: PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of -7.441 and -4.295 kcal/mol, correspondingly. Conclusion: PLP2's upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2's role in glioma modulation. Our research hints at PLP2's potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.
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Objective: In recent years, more and more cases of intracranial aneurysms (IAs) have been found in elderly patients, and neurosurgical interventions have increased, but there is still no consensus on the best treatment strategy for elderly patients. In elderly patients, endovascular coiling (EC) is more popular than surgical clipping (SC) due to its advantages of less trauma and faster recovery. However, SC has made great progress in recent years, significantly improving the prognosis of elderly patients. Therefore, it is necessary to further explore the effects of different treatment modalities on clinical prognosis, hospital stay, and hospital cost of elderly IA patients, and select the most appropriate treatment modalities. Methods: The authors retrospectively analyzed 767 patients with intracranial aneurysms admitted to the facility between August 2017 and December 2022. Prognostic risk factors and multivariate logistic regression were analyzed for elderly patients treated with EC or SC. The area under the receiver operating characteristic (ROC) curve was used to calculate the predictive power of each independent predictor between the treatment groups. Results: Our study included 767 patients with aneurysms, of whom 348 (45.4%) were elderly, 176 (22.9%) underwent endovascular coiling, and 172 (22.4%) underwent microsurgical clipping. A comparison of elderly patients treated with EC and SC showed a higher prevalence of hypertension in the EC group (P = 0.011) and a higher Hunt-Hess score on admission in the SC group (P = 0.010). Patients in the EC group had shorter hospital stays but higher costs (P = 0.000 and P = 0.000, respectively). Patients treated with SC had a higher incidence of postoperative cerebral infarction and poor prognosis (P = 0.002 and P = 0.008, respectively). Through multi-factor logistic analysis, it was found that age (OR 1.209, 95% CI 1.047-1.397, P = 0.010), length of stay (LOS) (OR 1.160, 95 CI% 1.041-1.289, P = 0.007), and complications (OR 31.873, 95 CI% 11.677-320.701, P = 0.000) was an independent risk factor for poor prognosis in elderly patients with EC. In elderly patients treated with SC, age (OR 1.105, 95% CI 1.010-1.209, P = 0.029) was an independent risk factor for poor prognosis. Conclusion: EC and SC interventions in elderly adults carry higher risks compared to non-older adults, and people should consider these risks and costs when making a decision between intervention and conservative treatment. In elderly patients who received EC or SC treatments, EC showed an advantage in improving outcomes in elderly patients although it increased the economic cost of the patient's hospitalization.
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Skin lesions not only disrupt appearance and barrier functionality but also lead to severe microbial infections and immune-inflammatory responses, seriously affect physical and mental health. In situ printing involves the direct deposition of bio-ink to create or repair damaged tissues or organs within a clinical setting. In this study, we designed and fabricated a novel portable in situ printer. This handheld instrument exhibits excellent printing performance, allowing hydrogels to be patterned and molded on surfaces according to specific requirements. By utilizing a dual-component hydrogels co-printing approach with high and low viscosities, we achieved in situ cell-laden printing using low-viscosity hydrogel. This demonstrates the advantages of the device in maintaining cell viability and achieving hydrogel structuring. This approach opens up the possibilities for the efficient encapsulation of active components such as drugs, proteins, and cells, enabling controlled macro- and micro-structuring of hydrogels. This breakthrough finding highlights the potential of our technical approach in dermatological treatment and wound repair, by dynamically adapting and regulating microenvironments in conjunction with hydrogel scaffolds and cell reparative impetus.
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Gesture recognition systems epitomize a modern and intelligent approach to rehabilitative training, finding utility in assisted driving, sign language comprehension, and machine control. However, wearable devices that can monitor and motivate physically rehabilitated people in real time remain little studied. Here, we present an innovative gesture recognition system that integrates hydrogel strain sensors with machine learning to facilitate finger rehabilitation training. PSTG (PAM/SA/TG) hydrogels are constructed by thermal polymerization of acrylamide (AM), sodium alginate (SA), and tannic acid-reduced graphene oxide (TA-rGO, TG), with AM polymerizing into polyacrylamide (PAM). The surface of TG has abundant functional groups that can establish multiple hydrogen bonds with PAM and SA chains to endow the hydrogel with high stretchability and mechanical stability. Our strain sensor boasts impressive sensitivity (Gauge factor = 6.13), a fast response time (40.5 ms), and high linearity (R2 = 0.999), making it an effective tool for monitoring human joint movements and pronunciation. Leveraging machine learning techniques, our gesture recognition system accurately discerns nine distinct types of gestures with a recognition accuracy of 100%. Our research drives wearable advancements, elevating the landscape of patient rehabilitation and augmenting gesture recognition systems' healthcare applications.
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Based on observations in China's east coastal oceans, we conducted a preliminary assessment of 16 sets of carbonic acid dissociation constants (K1* and K2*) by comparing spectrophotometrically measured pH values at 25 °C with those calculated from total alkalinity and dissolved inorganic carbon. We obtained that K1* and K2* often performed differently within different salinity ranges, and that the constants of Millero et al. (2002) (M02) demonstrated the best performance for the salinity range of 24-35. In contrast, the often recommended constants of Mehrbach et al. (1973) refit by Dickson and Millero (1987) (DM87-M) and Lucker et al. (2000) (L00) would underestimate pH at salinities of 24-30. This was mainly associated with the higher product of K1* and K2* by DM87-M and L00 than by M02 at this salinity range. Also, we found almost no differences between pH values calculated with DM87-M and L00.
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Carbono , Ácido Carbônico , Oceanos e Mares , Carbono/análise , Salinidade , ChinaRESUMO
BACKGROUND: Dermoscopic image segmentation using deep learning algorithms is a critical technology for skin cancer detection and therapy. Specifically, this technology is a spatially equivariant task and relies heavily on Convolutional Neural Networks (CNNs), which lost more effective features during cascading down-sampling or up-sampling. Recently, vision isotropic architecture has emerged to eliminate cascade procedures in CNNs as well as demonstrates superior performance. Nevertheless, it cannot be used for the segmentation task directly. Based on these discoveries, this research intends to explore an efficient architecture which not only preserves the advantages of the isotropic architecture but is also suitable for clinical dermoscopic diagnosis. METHODS: In this work, we introduce a novel Semi-Isotropic L-shaped network (SIL-Net) for dermoscopic image segmentation. First, we propose a Patch Embedding Weak Correlation (PEWC) module to address the issue of no interaction between adjacent patches during the standard Patch Embedding process. Second, a plug-and-play and zero-parameter Residual Spatial Mirror Information (RSMI) path is proposed to supplement effective features during up-sampling and optimize the lesion boundaries. Third, to further reconstruct deep features and get refined lesion regions, a Depth Separable Transpose Convolution (DSTC) based up-sampling module is designed. RESULTS: The proposed architecture obtains state-of-the-art performance on dermoscopy benchmark datasets ISIC-2017, ISIC-2018 and PH2. Respectively, the Dice coefficient (DICE) of above datasets achieves 89.63%, 93.47%, and 95.11%, where the Mean Intersection over Union (MIoU) are 82.02%, 88.21%, and 90.81%. Furthermore, the robustness and generalizability of our method has been demonstrated through additional experiments on standard intestinal polyp datasets (CVC-ClinicDB and Kvasir-SEG). CONCLUSION: Our findings demonstrate that SIL-Net not only has great potential for precise segmentation of the lesion region but also exhibits stronger generalizability and robustness, indicating that it meets the requirements for clinical diagnosis. Notably, our method shows state-of-the-art performance on all five datasets, which highlights the effectiveness of the semi-isotropic design mechanism.
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Dermoscopia , Neoplasias Cutâneas , Humanos , Dermoscopia/métodos , Neoplasias Cutâneas/diagnóstico , Pele/patologia , Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodosRESUMO
As the largest organ of the human body, the skin has a complex multi-layered structure. The composition of the skin includes cells, extracellular matrix (ECM), vascular networks, and other appendages. Because of the shortage of donor sites, skin substitutes are of great significance in the field of skin tissue repair. Moreover, skin models for disease research, drug screening, and cosmetic testing fall far short of the demand. Skin tissue engineering has made remarkable progress in developing skin models over the years. However, there are still several problems to be resolved. One of the crucial aspects is the lack of vascular systems for nutrient transport and waste disposal. Here, we will focus on the discussion and analysis of advanced manufacturing strategies for prevascularized skin, such as a scaffold-based method, cell coating technology, cell sheet engineering, skin-on-a-chip, and three-dimensional (3D) bioprinting. These key challenges, which restrict the prevascularized skin and provide perspectives on future directions will also be highlighted.
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Bioimpressão , Pele Artificial , Matriz Extracelular , Humanos , Impressão Tridimensional , Pele , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
Lithium is associated with oxidative stress and apoptosis, but the mechanism by which lithium protects against spinal cord injury remains poorly understood. In this study, we found that intraperitoneal administration of lithium chloride (LiCl) in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factor α, interleukin-6, and interleukin 1 ß. Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression, reducing the oxidative stress response, and inhibiting activation of the Nod-like receptor protein 3 inflammasome. We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells. We found that lithium reduced inflammation, oxidative damage, apoptosis, and necrosis and up-regulated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 in PC12 cells. All-trans retinoic acid, an Nrf2 inhibitor, reversed the effects of lithium. These results suggest that lithium exerts anti-inflammatory, anti-oxidant, and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury. This study was approved by the Animal Ethics Committee of Xi'an Jiaotong University (approval No. 2018-2053) on October 23, 2018.
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Persistent inflammation in the secondary spinal cord injury (SCI) is an important reason for the failure of nerve repair, which is partly due to the continuous activation of local M1-like macrophage/microglia. It is reported that extracellular trap (ET) has been a new way of cell death, which can be released by macrophages and named macrophage extracellular trap (Met). Furthermore, it exists widely in the pathophysiological process of many diseases, but it has been rarely studied in the field of SCI. In this study, we constructed a spinal cord contusion model and assessed the function outcome of SCI rats. We used immunofluorescence, flow cytometry, and transmission electron microscope (TEM) to demonstrate the existence of Mets. Besides, some related experiments had also been employed to explore the relationship between Mets and M1 polarization of macrophage/microglia. We also performed Co-IP and Western blotting to reveal a new extracellular proinflammatory signal pathway. Finally, we made a linear regression analysis between the concentrations of specific markers of Mets in human serum and ASIA scores. Briefly, our results suggested that macrophages infiltrated in SCI area could induce macrophage/microglia to differentiate into M1-like cells by releasing Mets, which may be achieved partly through LL37-P2X37-NF-κB signal pathway. However, limiting Mets could effectively inhibit M1 polarization and promote function recovery. In addition, the concentrations of Met related proteins in human serum showed high correlation with ASIA scores and could be applied to reflect the severity of SCI. In conclusion, Mets may be a new target for SCI therapy and a promising index for SCI assessment.
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Armadilhas Extracelulares , Traumatismos da Medula Espinal , Humanos , Ratos , Animais , NF-kappa B , Microglia , Transdução de Sinais , MacrófagosRESUMO
Background: Breast cancer is the most common cancer worldwide. Hypoxia and lactate metabolism are hallmarks of cancer. This study aimed to construct a novel hypoxia- and lactate metabolism-related gene signature to predict the survival, immune microenvironment, and treatment response of breast cancer patients. Methods: RNA-seq and clinical data of breast cancer from The Cancer Genome Atlas database and Gene Expression Omnibus were downloaded. Hypoxia- and lactate metabolism-related genes were collected from publicly available data sources. The differentially expressed genes were identified using the "edgeR" R package. Univariate Cox regression, random survival forest (RSF), and stepwise multivariate Cox regression analyses were performed to construct the hypoxia-lactate metabolism-related prognostic model (HLMRPM). Further analyses, including functional enrichment, ESTIMATE, CIBERSORTx, Immune Cell Abundance Identifier (ImmuCellAI), TIDE, immunophenoscore (IPS), pRRophetic, and CellMiner, were performed to analyze immune status and treatment responses. Results: We identified 181 differentially expressed hypoxia-lactate metabolism-related genes (HLMRGs), 24 of which were valuable prognostic genes. Using RSF and stepwise multivariate Cox regression analysis, five HLMRGs were included to establish the HLMRPM. According to the medium-risk score, patients were divided into high- and low-risk groups. Patients in the high-risk group had a worse prognosis than those in the low-risk group (P < 0.05). A nomogram was further built to predict overall survival (OS). Functional enrichment analyses showed that the low-risk group was enriched with immune-related pathways, such as antigen processing and presentation and cytokine-cytokine receptor interaction, whereas the high-risk group was enriched in mTOR and Wnt signaling pathways. CIBERSORTx and ImmuCellAI showed that the low-risk group had abundant anti-tumor immune cells, whereas in the high-risk group, immunosuppressive cells were dominant. Independent immunotherapy datasets (IMvigor210 and GSE78220), TIDE, IPS and pRRophetic analyses revealed that the low-risk group responded better to common immunotherapy and chemotherapy drugs. Conclusions: We constructed a novel prognostic signature combining lactate metabolism and hypoxia to predict OS, immune status, and treatment response of patients with breast cancer, providing a viewpoint for individualized treatment.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Biologia Computacional , Prognóstico , Imunoterapia , Aprendizado de Máquina , Hipóxia/genética , Serina-Treonina Quinases TOR , Receptores de Citocinas , Citocinas , Lactatos , Microambiente Tumoral/genéticaRESUMO
Breast cancer (BC) has the highest incidence rate of all cancers globally, with high heterogeneity. Increasing evidence shows that lactate and long non-coding RNA (lncRNA) play a critical role in tumor occurrence, maintenance, therapeutic response, and immune microenvironment. We aimed to construct a lactate-related lncRNAs prognostic signature (LRLPS) for BC patients to predict prognosis, tumor microenvironment, and treatment responses. The BC data download from the Cancer Genome Atlas (TCGA) database was the entire cohort, and it was randomly assigned to the training and test cohorts at a 1:1 ratio. Difference analysis and Pearson correlation analysis identified 196 differentially expressed lactate-related lncRNAs (LRLs). The univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to construct the LRLPS, which consisted of 7 LRLs. Patients could be assigned into high-risk and low-risk groups based on the medium-risk sore in the training cohort. Then, we performed the Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. The results indicated that the prognosis prediction ability of the LRLPS was excellent, robust, and independent. Furthermore, a nomogram was constructed based on the LRLPS risk score and clinical factors to predict the 3-, 5-, and 10-year survival probability. The GO/KEGG and GSEA indicated that immune-related pathways differed between the two-risk group. CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore (IPS) showed that low-risk patients had higher levels of immune infiltration and better immunotherapeutic response. The pRRophetic and CellMiner databases indicated that many common chemotherapeutic drugs were more effective for low-risk patients. In conclusion, we developed a novel LRLPS for BC that could predict the prognosis, immune landscape, and treatment response.