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1.
Article En | MEDLINE | ID: mdl-38824927

OBJECTIVE: Ovarian cancer is the second most common malignancy in women, but it is the most fatal gynecological tumor. Although it has a standard treatment regimen, resistance to chemotherapy makes patients more prone to early recurrence, leading to poor survival rate. Therefore, this study aimed to investigate the factors related to platinum resistance through a complete analysis of clinical data. DESIGN: This study collected clinical data of patients with ovarian cancer and divided the petients into platinum-sensitive and platinum-resistant groups.By comparing the differences in clinical data between the two groups, the key factors affecting platinum resistance were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected the clinical data of patients with epithelial ovarian cancer (EOC) who were admitted to the Department of Oncology of the General Hospital of Ningxia Medical University between January 1, 2019 and December 31, 2020. We conducted univariate and multivariate analyses and evaluated their overall survival and progression-free survival by using the Kaplan-Meier method. RESULTS: We enrolled 161 patients with EOC, of whom 124 demonstrated platinum sensitivity and 37 demonstrated platinum resistance after the initial platinum-based chemotherapy. Univariate analyses revealed that International Federation of Gynecology and Obstetrics (FIGO) stage, neoadjuvant chemotherapy, and Fagotti score were associated with an increased risk of platinum resistance for the first recurrence. In multivariate logistic regression analysis, only Fagotti score and neoadjuvant chemotherapy were associated with an increased risk of platinum resistance (odds ratio: 0.372 and 0.328, 95% confidence interval: 0.160-0.863 and 0.141-0.762, P = 0.021 and 0.010, respectively). LIMITATIONS: The sample size in this study is still relatively small, due to non-standard treatment of some patients,the absence of some clinial data,and the failure of follow-up,etc. CONCLUSION: Patients with EOC exhibiting platinum resistance had a very poor prognosis. Fagotti score and neoadjuvant chemotherapy appeared to increase the risk of platinum resistance at first recurrence.

2.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1523-1535, 2024 May 25.
Article Zh | MEDLINE | ID: mdl-38783813

The adoptive immunotherapy mediated by tumor-infiltrating lymphocytes (TILs) has shown definite efficacy against various solid tumors. However, the inefficiency of the conventional method based on in vitro expansion of TILs fails to achieve the cell count and high tumor-killing activity required for therapeutic purposes. This study investigated the effect of 3D tumor spheroids on the activation and expansion of TILs in vitro, aiming to provide a novel approach for the expansion of TILs. We procured TILs and primary tumor cells from surgical samples of lung cancer patients and then compared the impacts of lung cancer cell line NCI-H1975 and primary lung cancer cells cultured under 2D and 3D conditions on the activation, expansion, and anti-tumor activity of TILs. Furthermore, we added the programmed cell death protein 1 (PD-1) antibody into the co-culture of primary tumor cells and TILs within a 3D environment to assess the effects of the antibody on TILs. The results showed that compared with 2D cultured tumor cells, the 3D cultured H1975 cells significantly enhanced the expansion of TILs, increasing the proportion of CD3+/CD8+ cells in TILs to 61.6%. The 3D primary tumor model also enhanced the proportion of CD3+/CD8+ cells in TILs (45.5%, 54.4%), induced apoptosis of tumor epithelial cells and decreased the overall tumor cells survival rate (16.7%) after co-culture. PD-1 antibodies further improved the in vitro expansion capacity of TILs mediated by 3D tumor spheroids, resulting in the proportions of 50.9% and 57.0% for CD3+/CD8+ cells and enhancing the antitumor activity significantly (reducing the overall tumor survival rate to 9.36%). In summary, the use of 3D tumor spheroids significantly promoted the expansion and improved the anti-tumor effect of TILs, and the use of the PD-1 antibody further promoted the expansion and tumor-killing effect of TILs.


Lung Neoplasms , Lymphocytes, Tumor-Infiltrating , Spheroids, Cellular , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Spheroids, Cellular/immunology , Cell Line, Tumor , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Programmed Cell Death 1 Receptor/immunology , Immunotherapy, Adoptive , Coculture Techniques , Cell Culture Techniques , Tumor Cells, Cultured , Cell Proliferation
3.
Nat Commun ; 15(1): 3382, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643164

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.


Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Tumor Microenvironment , Organoids/pathology , Precision Medicine/methods
4.
Diabetes Obes Metab ; 26(7): 2673-2683, 2024 Jul.
Article En | MEDLINE | ID: mdl-38558498

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.


Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Male , Female , Prospective Studies , Middle Aged , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/etiology , United Kingdom/epidemiology , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Adult , Risk Factors , Body Mass Index , Smoking/adverse effects , Smoking/epidemiology , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Exercise , Follow-Up Studies , Blood Pressure , Incidence
5.
J Environ Sci (China) ; 142: 11-20, 2024 Aug.
Article En | MEDLINE | ID: mdl-38527877

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al2O3) and the effects of four oxides (SiO2, Al2O3, Fe2O3, and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al2O3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al2O3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO2 was better for the reduction of Na2CrO4 and K2CrO4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO4 decomposed above 700°C to form MgCr2O4, and the reaction between MgCrO4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl3, it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO2, Al2O3, and Fe2O3, which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment.


Oxides , Solid Waste , Silicon Dioxide , Chromium/analysis , Oxidation-Reduction , Incineration
6.
World J Surg Oncol ; 22(1): 81, 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38509620

BACKGROUND: This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC). METHODS: EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's performance. RESULTS: The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram's specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram's AUC was 0.949. CONCLUSION: A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.


Ovarian Neoplasms , Precision Medicine , Female , Humans , Carcinoma, Ovarian Epithelial/drug therapy , Nomograms , Platinum/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics
7.
Materials (Basel) ; 17(2)2024 Jan 10.
Article En | MEDLINE | ID: mdl-38255520

Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), ß-tricalcium phosphate (ß-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.

8.
Adv Mater ; : e2309618, 2023 Dec 25.
Article En | MEDLINE | ID: mdl-38145905

Space three dimension (3D) bioprinting provides a precise and bionic tumor model for evaluating the compound effect of the space environment on tumors, thereby providing insight into the progress of the disease and potential treatments. However, space 3D bioprinting faces several challenges, including prelaunch uncertainty, possible liquid leakage, long-term culture in space, automatic equipment control, data acquisition, and transmission. Here, a novel satellite-based 3D bioprinting device with high structural strength, small volume, and low weight (<6 kg) is developed. A microgel-based biphasic thermosensitive bioink and suspension medium that supports the on-orbit printing and in situ culture of complex tumor models is developed. An intelligent control algorithm that enables the automatic control of 3D printing, autofocusing, fluorescence imaging, and data transfer back to the ground is developed. To the authors' knowledge, this is the first time that on-orbit printing of tumor models is achieved in space with stable morphology and moderate viability via a satellite. It is found that 3D tumor models are more sensitive to antitumor drugs in space than on Earth. This study opens up a new avenue for 3D bioprinting in space and offers new possibilities for future research in space life science and medicine.

9.
Microsyst Nanoeng ; 9: 128, 2023.
Article En | MEDLINE | ID: mdl-37829156

Scanning probe lithography (SPL) is a promising technology to fabricate high-resolution, customized and cost-effective features at the nanoscale. However, the quality of nano-fabrication, particularly the critical dimension, is significantly influenced by various SPL fabrication techniques and their corresponding process parameters. Meanwhile, the identification and measurement of nano-fabrication features are very time-consuming and subjective. To tackle these challenges, we propose a novel framework for process parameter optimization and feature segmentation of SPL via machine learning (ML). Different from traditional SPL techniques that rely on manual labeling-based experimental methods, the proposed framework intelligently extracts reliable and global information for statistical analysis to fine-tune and optimize process parameters. Based on the proposed framework, we realized the processing of smaller critical dimensions through the optimization of process parameters, and performed direct-write nano-lithography on a large scale. Furthermore, data-driven feature extraction and analysis could potentially provide guidance for other characterization methods and fabrication quality optimization.

10.
ACS Appl Mater Interfaces ; 15(37): 43492-43502, 2023 Sep 20.
Article En | MEDLINE | ID: mdl-37691550

The convergence of 3D bioprinting with powerful manufacturing capability and cellular self-organization that can reproduce intricate tissue microarchitecture and function is a promising direction toward building functional tissues and has yet to be demonstrated. Here, we develop a granular aggregate-prevascularized (GAP) bioink for engineering highly vascularized bone tissues by capitalizing on the condensate-mimicking, self-organization, and angiogenic properties of prevascularized mesenchymal spheroids. The GAP bioink utilizes prevascularized aggregates as building blocks, which are embedded densely in extracellular matrices conducive to spontaneous self-organization. We printed various complex structures with high cell density (∼1.5 × 108 cells/cm3), viability (∼80%), and shape fidelity using GAP bioink. After printing, the prevascularized mesenchymal spheroids developed an interconnected vascular network through angiogenic sprouting. We printed highly vascularized bone tissues using GAP bioink and found that prevascularized spheroids were more conducive to osteogenesis and angiogenesis. We envision that the design of the GAP bioink could be further integrated with human-induced pluripotent stem cell-derived organoids, which opens new avenues to create patient-specific vascularized tissues for therapeutic applications..


Bioprinting , Humans , Bone and Bones , Osteogenesis , Engineering , Extracellular Matrix
11.
Biofabrication ; 15(4)2023 07 20.
Article En | MEDLINE | ID: mdl-37429291

Three-dimensional bioprinting has emerged as an appealing approach for creating functional tissues; however, a lack of suitable bioinks with high cell density and printability has greatly limited our ability to print functional tissues. We address this limitation by developing a granular cell aggregate-based biphasic (GCAB) bioink based on densely packed cell aggregates. The GCAB bioink exhibited the desired shear-thinning and shear-recovery properties for extrusion bioprinting and hyperelastic behaviors postprinting for modeling the mechanical characteristics of soft biological tissues. The GCAB bioink displayed a high cell density (∼1.7 × 108cells cm-3) without compromising viability (∼83%). We printed dense hepatic tissue constructs with enhanced vascularization and metabolic functions by preorganization of GCAB bioink with a defined heterogeneous microenvironment. By simultaneously printing the GCAB bioink and an endothelial cell-laden gelatin bioink, we successfully produced functional hepatic tissues with a high cell density and a perfusable vascular network. The design of the generalizable GCAB bioink opens new avenues to create functional tissues for therapeutic applications.


Bioprinting , Tissue Scaffolds , Tissue Engineering/methods , Bioprinting/methods , Printing, Three-Dimensional , Gelatin
12.
Arterioscler Thromb Vasc Biol ; 43(9): 1684-1699, 2023 09.
Article En | MEDLINE | ID: mdl-37409531

BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.


MicroRNAs , RNA, Long Noncoding , Vascular Calcification , Humans , Rats , Animals , MicroRNAs/metabolism , Aldosterone/toxicity , RNA, Long Noncoding/metabolism , Osteogenesis , Vascular Calcification/chemically induced , Vascular Calcification/genetics , Vascular Calcification/metabolism , Myocytes, Smooth Muscle/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism
13.
Am J Med ; 136(9): 910-917.e4, 2023 09.
Article En | MEDLINE | ID: mdl-37225117

BACKGROUND: Reduced lung function has been linked to cardiovascular disease, but population-based evidence on the relationship between lung function decline and coronary artery calcium (CAC) progression is rare. METHODS: A total of 2694 participants (44.7% men) with a mean ± standard deviation age of 40.4 ± 3.6 years from the Coronary Artery Risk Development in Young Adults (CARDIA) were included. The rates of decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over a 20-year period were calculated for each participant and categorized into quartiles. The primary outcome was CAC progression. RESULTS: During a mean follow-up of 8.9 years, 455 (16.9%) participants had CAC progression. After adjusting for traditional cardiovascular risk factors, the hazard ratios (95% confidence intervals [CIs]) for CAC progression were higher for participants in the 2nd (Q2), 3rd (Q3), and highest quartiles (Q4) of FVC decline compared with those in the lowest quartile (Q1): 1.366 (1.003-1.861), 1.412 (1.035-1.927), and 1.789 (1.318-2.428), respectively. Similar trends were observed for the association between FEV1 and CAC progression. The association remained robust across a series of sensitivity analyses and all subgroups. CONCLUSIONS: A faster decline in FVC or FEV1 during young adulthood is independently associated with an increased risk of CAC progression in midlife. Maintaining optimal lung function during young adulthood may improve future cardiovascular health.


Calcium , Coronary Artery Disease , Male , Young Adult , Humans , Adult , Female , Lung/diagnostic imaging , Coronary Artery Disease/epidemiology , Vital Capacity , Risk Factors , Forced Expiratory Volume
14.
Ann Med ; 55(1): 2209334, 2023 12.
Article En | MEDLINE | ID: mdl-37155413

BACKGROUND & AIMS: Individuals with high blood pressure (BP) have varying risks of cardiovascular events due to other coexisting factors. We aimed to identify the predictors of long-term absence of coronary artery calcium (CAC) in individuals with high BP, which is an indicator of healthy arterial aging and can guide preventive strategies. METHODS: We analyzed data from participants with high BP (≥120/80 mm Hg) in the Multi-Ethnic Study of Atherosclerosis who had baseline CAC = 0 and underwent a second CAC scanning after 10 years. We used multivariable logistic regression to evaluate the association between various risk factors for atherosclerotic cardiovascular disease (ASCVD) and long-term CAC = 0. We also calculated the area under the receiver operating characteristic curve (AUC) to predict the phenotype of healthy arterial aging in this population. RESULTS: We included 830 participants (37.6% male, mean ± SD age of 59.4 ± 8.7 years). During follow-up, 46.5% of participants (n = 386) had CAC = 0, and they were younger and had fewer metabolic syndrome components. Adding ASCVD risk factors to the demographic model (age, sex, and ethnicity) moderately increased the predictive value for long-term CAC = 0 (AUC: demographic model + ASCVD risk factors vs. demographic model alone, 0.653 vs. 0.597, p < .001; category net reclassification improvement = 0.104, p = .044; integrated discrimination improvement = 0.040, p < .001). CONCLUSION: In individuals with high BP and initial CAC = 0, over 40% maintained CAC = 0 during a 10-year follow-up, which was associated with fewer ASCVD risk factors. These findings may have implications for preventive strategies in individuals with high BP.Clinical Trial registration number: The MESA was registered at clinical trials. gov as NCT00005487.KEY MESSAGESNearly half (46.5%) of individuals with high blood pressure (BP) maintained a long-term absence of coronary artery calcium (CAC) during a 10-year follow-up, and this was associated with a 66.6% lower risk of atherosclerotic cardiovascular disease (ASCVD) events compared to those who developed incident CAC.Individuals with high BP, who are usually assumed to have an increased risk of ASCVD, exhibit significant heterogeneity in their ASCVD risk; those who maintain CAC = 0 have a lower ASCVD risk.Adding overall ASCVD risk factors to demographic information resulted in a moderate improvement in predicting long-term CAC = 0.


Atherosclerosis , Cardiovascular Diseases , Coronary Artery Disease , Hypertension , Vascular Calcification , Female , Humans , Male , Calcium , Cardiovascular Diseases/epidemiology , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Vessels/diagnostic imaging , Hypertension/epidemiology , Risk Assessment/methods , Risk Factors , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology
15.
Bioact Mater ; 26: 216-230, 2023 Aug.
Article En | MEDLINE | ID: mdl-36936809

The bio-engineered ovary is an essential technology for treating female infertility. Especially the development of relevant in vitro models could be a critical step in a drug study. Herein, we develop a semi-opened culturing system (SOCS) strategy that maintains a 3D structure of follicles during the culture. Based on the SOCS, we further developed micro-cavity ovary (MCO) with mouse follicles by the microsphere-templated technique, where sacrificial gelatin microspheres were mixed with photo-crosslinkable gelatin methacryloyl (GelMA) to engineer a micro-cavity niche for follicle growth. The semi-opened MCO could support the follicle growing to the antral stage, secreting hormones, and ovulating cumulus-oocyte complex out of the MCO without extra manipulation. The MCO-ovulated oocyte exhibits a highly similar transcriptome to the in vivo counterpart (correlation of 0.97) and can be fertilized. Moreover, we found that a high ROS level could affect the cumulus expansion, which may result in anovulation disorder. The damage could be rescued by melatonin, but the end of cumulus expansion was 3h earlier than anticipation, validating that MCO has the potential for investigating ovarian toxic agents in vitro. We provide a novel approach for building an in vitro ovarian model to recapitulate ovarian functions and test chemical toxicity, suggesting it has the potential for clinical research in the future.

16.
Adv Healthc Mater ; 12(19): e2300607, 2023 07.
Article En | MEDLINE | ID: mdl-36975154

The formation of multiscale vascular networks is essential for the in vitro construction of large-scale biomimetic cardiac tissues/organs. Although a variety of bioprinting processes have been developed to achieve the construction of mesoscale and large-scale blood vessels, the formation of microvascular networks still mainly depends on the self-assembly behavior of endothelial cells (ECs), which is inefficient and demanding without appropriate stimulus. To address this problem, the elongation and connection of endothelial cells in engineered cardiac tissue (ECT) are sought to promote by electrical stimulation (ES) to achieve vascularization. As proof of the concept, bio-inks are composed of GelMA/fibrin hydrogel, human pluripotent stem cells induced cardiomyocytes (iPSC-CM), and human umbilical vein endothelial cells (HUVEC) are used for the bioprinting of ECTs. It is demonstrated that electrical stimulation significantly promotes the elongation, migration, and interconnection of HUVECs in ECT and increases the expression of related genes. Moreover, ES also enhances the secretion of signal factors interacting between CMs and HUVECs. It seems that the HUVECs further strengthen the contractility of cardiac tissue. Taken together, electrical stimulation promotes vascularization and CMs functionalization in ECT, which has important application potential in the fabrication of vascularized ECT and its clinical transplantation.


Biomimetics , Tissue Engineering , Humans , Human Umbilical Vein Endothelial Cells/metabolism , Myocytes, Cardiac , Electric Stimulation , Tissue Scaffolds
17.
Adv Sci (Weinh) ; 10(12): e2205744, 2023 04.
Article En | MEDLINE | ID: mdl-36808712

Nerve guidance conduits (NGCs) have become a promising alternative for peripheral nerve regeneration; however, the outcome of nerve regeneration and functional recovery is greatly affected by the physical, chemical, and electrical properties of NGCs. In this study, a conductive multiscale filled NGC (MF-NGC) consisting of electrospun poly(lactide-co-caprolactone) (PCL)/collagen nanofibers as the sheath, reduced graphene oxide /PCL microfibers as the backbone, and PCL microfibers as the internal structure for peripheral nerve regeneration is developed. The printed MF-NGCs presented good permeability, mechanical stability, and electrical conductivity, which further promoted the elongation and growth of Schwann cells and neurite outgrowth of PC12 neuronal cells. Animal studies using a rat sciatic nerve injury model reveal that the MF-NGCs promote neovascularization and M2 transition through the rapid recruitment of vascular cells and macrophages. Histological and functional assessments of the regenerated nerves confirm that the conductive MF-NGCs significantly enhance peripheral nerve regeneration, as indicated by improved axon myelination, muscle weight increase, and sciatic nerve function index. This study demonstrates the feasibility of using 3D-printed conductive MF-NGCs with hierarchically oriented fibers as functional conduits that can significantly enhance peripheral nerve regeneration.


Nerve Regeneration , Printing, Three-Dimensional , Sciatic Nerve , Electrochemical Techniques , Neurites , Animals , Rats , Cell Line
18.
Adv Mater ; 35(22): e2205082, 2023 Jun.
Article En | MEDLINE | ID: mdl-36796025

Creating functional tissues and organs in vitro on demand is a major goal in biofabrication, but the ability to replicate the external geometry of specific organs and their internal structures such as blood vessels simultaneously remains one of the greatest impediments. Here, this limitation is addressed by developing a generalizable bioprinting strategy of sequential printing in a reversible ink template (SPIRIT). It is demonstrated that this microgel-based biphasic (MB) bioink can be used as both an excellent bioink and a suspension medium that supports embedded 3D printing due to its shear-thinning and self-healing behavior. When encapsulating human-induced pluripotent stem cells, the MB bioink is 3D printed to generate cardiac tissues and organoids by extensive stem cell proliferation and cardiac differentiation. By incorporating MB bioink, the SPIRIT strategy enables the effective printing of a ventricle model with a perfusable vascular network, which is not possible to fabricate using extant 3D printing strategies. This SPIRIT technique offers an unparalleled bioprinting capability to replicate the complex organ geometry and internal structure in a faster manner, which will accelerate the biofabrication and therapeutic applications of tissue and organ constructs.


Bioprinting , Tissue Engineering , Humans , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Bioprinting/methods , Organoids , Printing, Three-Dimensional
19.
Environ Sci Pollut Res Int ; 30(12): 34009-34021, 2023 Mar.
Article En | MEDLINE | ID: mdl-36508103

The direct aqueous mineral carbonation of wood combustion ash (WCA), which is a representative high-calcium waste from combustion process, was systematically investigated by varying complex operating conditions, including reaction time, liquid-to-solid ratio (L/S), CO2 concentration, and particle size. The WCA exhibited high CO2 sequestration characteristics with an optimal carbonation efficiency of 76.4%, corresponding to a CO2 sequestration capacity of 0.314 g CO2/g WCA. In addition to solid carbonates, dry residues from liquid products with high potassium contents are potential feedstocks for quality potash fertilizer. Modified shrinking core models based on diffusion-controlled mechanism were proposed to evaluate the carbonation process. The theoretical framework assumes a contracting interface mechanism where active CaO reacts with CO2 to form a product layer. The effective diffusion coefficient of CO2 through the product layer decreases over time, giving deficient carbonation efficiency. The newly proposed models corresponding to different geometrical dimensions provided more perfect fit to the experimental data when compared with the most commonly used kinetic equations. The low apparent activation energy of the carbonation reaction demonstrated the diffusion-controlled mechanism. This work is useful for improving the economics and feasibility of bioenergy carbon capture and storage (CCS) technology chain.


Carbon Dioxide , Wood , Carbon Dioxide/chemistry , Kinetics , Carbonates/chemistry , Minerals/chemistry , Coal Ash/chemistry
20.
Environ Res ; 216(Pt 3): 114699, 2023 Jan 01.
Article En | MEDLINE | ID: mdl-36351474

The photocatalysis conversion of CO2 into fuels has become an encouraging method to address climate and energy issues as a long-term solution. Single material suffers poor yield due to low light energy utilization and high recombination rate of photoinduced electron-hole pairs. It is an efficient approach to construct heterojunction through two or three materials to improve the photocatalytic performance. Recently, 2D-based heterojunction is getting popular for outstanding properties, such as special light collecting structure to enhance light harvest, intimate interface to facilitate charge transfer and separation, and large specific surface area to provide abundant reactive sites. Recently, some new 2D-based heterostructures materials (both structure and composition) have been developed with excellent performance. 2D materials exert structural and functional advantages in these fine composite photocatalysts. In this review, the literatures about the photocatalytic conversion of CO2 are mainly summarized based on overall structure, interface type and material type of 2D-based heterojunction, with special attention given to the preparation, characterization, structural advantages and reaction mechanism of novel 2D-based heterojunction. This work is in hope of offering a basis for designing improved composite photocatalyst for CO2 photoreduction.

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