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1.
Am J Nephrol ; : 1-15, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35576899

RESUMO

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. RESULTS: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: -2.56 to 5.23], 3.50 [95% CI: -0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10-3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52-5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. CONCLUSION: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

2.
Front Oncol ; 12: 878513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530358

RESUMO

Objectives: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and characterized by high aggressiveness and extremely poor prognosis. Increasing evidence has suggested that circular RNAs (circRNAs), which are highly stable, play crucial roles in the progression of multiple malignancies. However, the roles of circRNAs in HCC remain elusive. Materials and Methods: The expression patterns of circRNAs in HCC were identified by qRT-PCR. A series of functional experiments both in vivo and in vitro were used to determine the role of circERBIN in HCC proliferation. Bioinformatics and an RNA pulldown assay were used to identify potential downstream targets of circERBIN. Results: The expression of circERBIN was upregulated in HCC cell lines and tissues, which was predictive of a poor prognosis in HCC patients. Elevated circERBIN promoted G1/S transition of HCC cells, thus facilitating the proliferation and tumorigenesis of HCC cells. Mechanistic investigations revealed that circERBIN regulated HCC proliferation by acting as a sponge of miR-1263, which subsequently targeted cyclin dependent kinase 6 and controlled G1/S transition. Conclusion: Taken together, these results determined that circERBIN functions as an important epigenetic regulator in HCC development, highlighting that circERBIN is a promising target for treatment of HCC.

3.
Surg Endosc ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534733

RESUMO

BACKGROUND: Pancreatoduodenectomy is the only potentially curative treatment for distal cholangiocarcinoma (DCC). In this study, we sought to compare the perioperative and oncological outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) based on a multicenter propensity score-matched study. METHODS: Consecutive patients with DCC who underwent RPD or OPD from five centers in China between January 2014 and June 2019 were included. A 1:1 propensity score matching (PSM) was performed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: A total of 217 patients and 228 patients underwent RPD and OPD, respectively. After PSM, 180 patients in each group were enrolled. There were no significant differences in operative time, lymph node harvest, intraoperative transfusion, vascular resection, R0 resection, postoperative major morbidity, reoperation, 90-day mortality, and long-term survival between the two groups before and after PSM. Whereas, compared with the OPD group, the RPD group had significantly lower estimated blood loss (150.0 ml vs. 250.0 ml; P < 0.001), and a shorter postoperative length of stay (LOS) (12.0 days vs. 15.0 days; P < 0.001). Multivariable analysis showed carbohydrate antigen 19-9 (CA19-9), R0 resection, N stage, perineural invasion, and tumor differentiation significantly associated with OS and RFS of these patients. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(4): 366-371, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35527409

RESUMO

OBJECTIVES: To investigate the influencing factors for the quality of bowel preparation before colonoscopy in children and the association of the interval from the last administration of laxative to the start of colonoscopy (shortly referred to as waiting time) with the quality of bowel preparation. METHODS: A retrospective analysis was performed for the children who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University, from January to November 2020, and received bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy. According to the score of Boston bowel preparation scale, they were divided into two groups: adequate bowel preparation group (n=337) and inadequate bowel preparation group (n=30). Related data were collected from the children in both groups, including general information, possible influencing factors for the quality of bowel preparation, adverse reactions associated with bowel preparation, duration of colonoscopy, and postoperative diagnosis. Univariate and multivariate analyses were used to explore the influencing factors for the quality of bowel preparation. RESULTS: The univariate analysis showed that age, body weight, and waiting time were associated with inadequate bowel preparation (P<0.05). The multivariate analysis showed that older age (OR=2.155, 95%CI: 1.087-4.273, P=0.028) and longer waiting time (OR=1.559, 95% CI: 1.191-2.041, P=0.001) were independent risk factors for inadequate bowel preparation. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of waiting time was 5.5 hours in determining whether bowel preparation was adequate or not, with a sensitivity of 90.0%, a specificity of 50.7%, and an area under the ROC curve of 0.708. After grouping based on waiting time, it was found that the incidence rate of inadequate bowel preparation in the ≥5.5 hours group was significantly higher than that in the <5.5 hours group [14.0% (27/193) vs 1.7% (3/174), P<0.001]. CONCLUSIONS: For children who use polyethylene glycol electrolyte powder combined with diet control for bowel preparation, older age is an independent risk factor for inadequate bowel preparation before colonoscopy, which may be associated with an insufficient dose of polyethylene glycol in older children. Longer waiting time is also an independent risk factor for inadequate bowel preparation, and it is recommended that the waiting time should not exceed 5.5 hours.


Assuntos
Catárticos , Colonoscopia , Criança , Dieta , Eletrólitos , Humanos , Polietilenoglicóis/efeitos adversos , Pós , Estudos Retrospectivos
5.
Phys Med Biol ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545078

RESUMO

Proton therapy requires accurate dose calculation for treatment planning to ensure the conformal doses are precisely delivered to the targets. The conversion of CT numbers to material properties is a significant source of uncertainty for dose calculation. The aim is to develop a physics-informed deep learning (PIDL) framework to derive accurate mass density and relative stopping power (RSP) maps from dual-energy computed tomography (DECT) images. The PIDL framework allows deep learning (DL) models to be trained with a physics loss function, which includes a physics model to constrain DL models. Five DL models were implemented including fully connected neural networks (FCNN), dual-FCNN (DFCNN), and three variants of ResNet: ResNet-v1 (RN-v1), ResNet-v2 (RN-v2), and dual-ResNet-v2 (DRN-v2). Two empirical DECT models were implemented to compare with the PIDL method. An artificial neural network (ANN) and the five DL models trained with and without physics loss were explored to evaluate the PIDL framework. DL training data were from CIRS electron density phantom 062M (Computerized Imaging Reference Systems, Inc., Norfolk, VA). The performance of DL models was tested by CIRS adult male, adult female, and 5-year-old child anthropomorphic phantoms. For density map inference, the physics-informed RN-v2 was 3.3%, 2.9% and 1.9% more accurate than ANN for the adult male, adult female, and child phantoms. The physics-informed DRN-v2 was 0.7%, 0.6%, and 0.8% more accurate than DRN-v2 without physics training for the three phantoms, respectfully. The results indicated that physics-informed training could reduce uncertainty when ANN/DL models without physics training were insufficient to capture data structures or derived significant errors. DL models could also achieve better image noise control compared to the empirical DECT parametric mapping methods. The proposed PIDL framework can potentially improve proton range uncertainty by offering accurate material properties conversion from DECT.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35551564

RESUMO

PURPOSE: To study the associations between fetal fraction at the first trimester and subsequent adverse pregnancy outcomes (APOs) in IVF singleton pregnancies with single embryo transfer from frozen cycles. METHODS: This is a single-center retrospective cohort study on IVF singleton pregnancies with single embryo transfer from frozen cycles. A total of 8457 women were collected between March 2015 and September 2018 from the Center for Reproductive Medicine, Shandong University, China. Participants underwent cell-free DNA (cfDNA) sequencing at 11-13 weeks' gestation. Multivariable logistic regressions were performed with the risk of APOs based on various predictor variables. RESULTS: A total of 8457 women were included in the analysis of which 1563 (18.48%) women developed one or more APOs. The hypertensive disorders of pregnancy (HDP) (N = 515), gestational diabetes mellitus (GDM) (N = 684), preterm birth (PTB) (N = 567), and low birth weight (LBW) (N = 306) groups had lower fetal fraction compared with the no pregnancy complication (NPC) group (all p values < 0.05). Based on the multivariable logistic regression results, the optimal cutoff values of fetal fraction were 9.30%, 12.54%, 9.10%, 12.65%, and 13.83% for at least one APO, HDP, GDM, PTB, and LBW, respectively. After adjustment for potential maternal confounders, women in the low fetal fraction (LFF) group had a higher risk for the APOs compared with high fetal fraction (HFF) group. CONCLUSIONS: The fetal fraction in HDP, GDM, PTB, and LBW groups were lower than NPC group in IVF singleton pregnancies with single embryo transfer from frozen cycles in China.

7.
Front Pharmacol ; 13: 806950, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548338

RESUMO

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis. Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery. Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019 were included. We evaluated the postoperative flatus time between recipients who received loading plus maintenance dose of DEX (LMD group, 237 recipients) and those who recieved maintenance dose of DEX (MD group, 302 recipients). Data were analyzed by logical regression and stratified and interaction analyses. The simulated pharmacokinetics of two DEX regimens was compared using the Tivatrainer software. Thirty paired blood samples from patients whose propensity scores matched with POGD-related factors at 24 h postoperatively were randomly selected, and their tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), d-lactate (DLA), acetylcholine (Ach), interleukin (IL)-10, lipopolysaccharide (LPS), IL-6, and inducible nitric oxide synthase (iNOS) levels were measured. Setting: Operating rooms and general surgery wards. Participants: Among the 644 patients undergoing colorectal surgery, 12 who had a colostomy, 26 without Dex infusion, 20 whose Dex administration mode cannot be classified, and 47 with a history of intestinal surgery were excluded. A total of 539 patients were included. Result: Compared with the MD group, the LMD group had a shorter recovery time to flatus; lower incidences of nausea, vomiting, abdominal distension, and abdominal pain (p < 0.05); and a slightly decreased heart rate. The LMD group was the independent factor of POGD (OR = 0.59, 95% CI = 0.41-0.87, p = 0.007) without being reversed in stratified and interaction analyses and had higher Dex plasma concentration from skin incision to 8 h postoperatively. The LMD group had a 39% and 43% increase in Ach and IL-10 levels, respectively, and a 33%-77% decrease in TNF-α, IL-6, COX-2, iNOS, LPS, and DLA levels (p < 0.05). Conclusion: Adding an extra loading dose of Dex can increase parasympathetic tone and decrease inflammation; hence, it can enhance postoperative gastrointestinal function recovery following colorectal surgery.

8.
Polymers (Basel) ; 14(9)2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35566914

RESUMO

In order to solve defects such as poor integrity, delamination failure, and narrow absorption bandwidth, three-dimensional (3D) gradient honeycomb woven composites (GHWCs) with triangular sections were designed and prepared. Three-dimensional gradient honeycomb woven fabric was crafted with carbon fiber (CF) filaments and basalt fiber (BF) filaments as raw materials on an ordinary loom. Then, the 3D honeycomb woven fabric filled with rigid polyurethane foam was used as the reinforcement, and epoxy resin (EP) doped with carbon black (CB) and carbonyl iron powder (CIP) was conducted as the matrix. The 3D GHWC with triangular sections, which had both EM-absorbing and load-bearing functions, was prepared by the VARTM process. Through the macro test and micro characterization of 3D GHWCs with triangular sections, the overall absorbing properties and mechanical properties of the materials were analyzed. Moreover, the EM-absorbing mechanism and failure mode of the materials were clarified in this work. The results indicated that the CF filament reflective layer effectively improved the EM-absorbing and mechanical properties. Adding a CB/CIP-absorbing agent enhanced the overall EM-absorbing property but reduced the mechanical properties. The increasing number of gradient layers increased the maximum bending load, but the EM-absorbing performance first increased and then decreased. When the thickness was 15 mm, the maximum bending load was 3530 N, and the minimum reflection loss (RLmin) was -21.6 dB. The synergistic effects of EM-absorbing and mechanical properties were the best right now. In addition, this work provided a feasible strategy that adjusting the type of absorber and gradient aperture size ratio could meet the unique requirements of absorbing frequency and intensity, which has excellent application prospects in civil and military fields.

9.
Mol Ecol Resour ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570323

RESUMO

Passive collection is an emerging sampling method for environmental DNA (eDNA) in aquatic systems. Passive eDNA collection is inexpensive, efficient, and requires minimal equipment, making it suited to high density sampling and remote deployment. Here, we compare the effectiveness of nine membrane materials for passively collecting fish eDNA from a 3 million litre marine mesocosm. We submerged materials (cellulose, cellulose with 1% and 3% chitosan, cellulose overlayed with electrospun nanofibers and 1% chitosan, cotton fibres, hemp fibres and sponge with either zeolite or active carbon) for intervals between five and 1080 minutes. We show that for most materials, with as little as five minutes submersion, mitochondrial fish eDNA measured with qPCR, and fish species richness measured with metabarcoding, was comparable to that collected by conventional filtering. Furthermore, PCR template DNA concentrations and species richness were generally not improved significantly by longer submersion. Species richness detected for all materials ranged between 11 to 37 species, with a median of 27, which was comparable to the range for filtered eDNA (19-32). Using scanning electron microscopy, we visualised biological matter adhered to the surface of materials, rather than entrapped, with images also revealing a diversity in size and structure of putative eDNA particles. Environmental DNA can be collected rapidly from seawater with a passive approach and using a variety of materials. This will suit cost and time-sensitive biological surveys, and where access to equipment is limited.

10.
Ann Transl Med ; 10(8): 446, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571425

RESUMO

Background: To explore whether maternal obesity inhibits placental angiogenesis through down-regulation of Sirtuin 1/Peroxisome proliferator-activated receptor-γ coactivator-1α (SIRT1/PGC-1α) signaling pathway. Methods: In a rat model of pre-pregnancy obesity, rats were sacrificed at embryonic day (E)18.5. Maternal characteristics were measured. Placentas were collected to observe the pathological changes and angiogenesis using hematoxylin-eosin (HE) staining and platelet endothelial cell adhesion molecule-1 [PECAM-1/CD31 (CD31)] immunohistochemical (IHC) staining, and the expression of the SIRT1/PGC-1α signaling pathway was also analyzed using western blotting and quantitative real-time polymerase chain reaction (qPCR). In in vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated under high fat conditions. We activated and inhibited the SIRT1/PGC-1α signaling pathway to determine the proliferation, angiogenic tube formation, and migration capacity of endothelial cells. Cell counting kit-8 (CCK-8) assays, tubule formation assays, and scratch wound-healing migration assays were also performed. Results: In vivo results showed that compared with the control group, the high-fat diet (HFD) group were heavier and their plasma triglyceride and total cholesterol contents were higher. The ratio of fetal weight to placental weight was reduced in the HFD group compared to the control group. In the HFD group, placental angiogenesis was decreased, and the SIRT1/PGC-1α signaling pathway was down-regulated compared with that in the control group. The results of in vitro experiments showed that SRT1720 reduced SIRT1/PGC-1α and vascular endothelial growth factor (VEGFA) expression inhibition induced by high fat stress, while EX-527 increased SIRT1/PGC-1α and VEGFA expression inhibition. Compared with the control group, maternal obesity impaired placental angiogenesis and reduced the proliferation and migration of HUVECs. Conclusions: The results suggest that maternal obesity impairs placental angiogenesis. They also provide experimental evidence that activation of the SIRT1/PGC-1α signaling pathway improves angiogenesis in vitro.

11.
Brain Res Bull ; 185: 91-98, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35550155

RESUMO

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

12.
Front Endocrinol (Lausanne) ; 13: 829153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574016

RESUMO

Objective: To characterize the status of ovarian reserve and ART outcomes in BPES women and provide informative reference for clinical diagnosis and treatment. Methods: Twenty-one women with BPES were screened for mutations in the FOXL2 gene and underwent assisted reproductive technology (ART) treatment. Indicators for ovarian reserve and ART outcomes were compared between patients with and without FOXL2 mutations. Additionally, ART outcomes were compared among patients with different subtypes of FOXL2 mutations. Results: A total of 13 distinct heterozygous variants in the FOXL2 gene were identified in 80.95% of BPES women, including 4 novel mutations with plausible pathogenicity (c.173_175dup, c.481C>T, c.576del and c.675_714del). Compared to non-mutation group, patients with FOXL2 mutations had elevated levels of FSH (P=0.007), decreased AMH levels (P=0.012) and less AFC (P=0.015). They also had worse ART outcomes with large amount of Gn dosage (P=0.008), fewer oocytes (P=0.001), Day3 good quality embryos (P=0.001) and good quality blastocysts (P=0.037), and a higher cancellation rate (P=0.272). High heterogeneity of ART outcomes existed in BPES patients with different FOXL2 mutation types. Conclusions: BPES patients with FOXL2 mutations had diminished ovarian reserve and adverse ART outcomes. The genotype-reproductive phenotype correlations were highly heterogeneous and cannot be generalized. Genetic counseling for fertility planning and preimplantation or prenatal genetic diagnosis to reduce offspring inheritance are recommended.

13.
Acta Trop ; 232: 106469, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35430263

RESUMO

Prosthogonimus cuneatus and Prosthogonimus pellucidus (Trematoda: Prosthogonimidae) are common flukes of poultry and other birds which can cause severe impacts on animal health and losses to the poultry industry. However, there are limited studies on the molecular epidemiology, population genetics, and systematics of Prosthogonimus species. In the present study, the complete mitochondrial (mt) genomes of P. cuneatus and P. pellucidus were determined to be 14,829 bp and 15,013 bp in length, respectively. Both mt genomes contain 12 protein-coding genes (PCGs) (cox1-3, nad1-6, nad4L, cytb, and atp6), 22 transfer RNA genes, two ribosomal RNA genes, and one non-coding region. Our comparative analysis shows that the atp6 genes of P. cuneatus and P. pellucidus are longer than any previously published atp6 genes of other trematodes. The lengths of the atp6 genes of P. cuneatus and P. pellucidus in this study seem unusual, and should therefore be studied further. The mt genes of P. cuneatus and P. pellucidus are transcribed in the same direction, and the gene arrangements are identical to those of Plagiorchis maculosus, Tamerlania zarudnyi, and Tanaisia sp., but different from those of Eurytrema pancreaticum, Dicrocoelium chinensis, and Brachycladium goliath. The mt genome A + T contents of P. cuneatus and P. pellucidus are 64.47% and 65.34%, respectively. In the 12 PCGs, ATG is the most common initiation codon, whereas TAG is the most common termination codon. The sequence identity of the same 12 PCGs among the eight trematodes (P. cuneatus, P. pellucidus, Pl. maculosus, D. chinensis, E. pancreaticum, B. goliath, T. zarudnyi, Tanaisia sp.) of Xiphidiata are 55.5%-81.7% at the nucleotide level and 43.9%-82.5% at the amino acid level. The nucleotide similarities among the complete mt genomes of the eight trematodes range from 54.1%-81.5%. Phylogenetic analysis based on the aligned concatenated amino acid sequences of the 12 PCGs shows that P. cuneatus and P. pellucidus cluster together and are sister to T. zarudnyi and Tanaisia sp., and this clade is more closely related to E. pancreaticum, Dicrocoelium spp. and Lyperosomum longicauda in the family Dicrocoeliidae, than it is to species in the families Plagiorchiidae and Brachycladiidae. These are the first reported complete mt genomes of Prosthogonimidae, and these data will provide additional molecular resources for further studies of Prosthogonimidae taxonomy, population genetics, and systematics.

14.
Adv Mater ; : e2110356, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439839

RESUMO

Wide-bandgap (∼1.8 eV) perovskite is an crucial component to pair with narrow-bandgap perovskite in low-cost monolithic all-perovskite tandem solar cells. However, the stability and efficiency of wide-bandgap perovskite solar cells are constrained by the light-induced halide segregation and by the large photovoltage deficit. Here we report a steric engineering to obtain high-quality and photostable wide-bandgap perovskites (∼1.8 eV) suitable for all-perovskite tandems. By alloying dimethylammonium and chloride into the mixed-cation mixed-halide perovskites, wide bandgaps are obtained with much lower bromide contents while the lattice strain and trap densities are simultaneously minimized. The wide-bandgap perovskite solar cells exhibit considerably improved performance and photostability, retaining >90% of their initial efficiencies after 1000 hours of operation at maximum power point. With the triple-cation/triple-halide wide-bandgap perovskites enabled by steric engineering, we further obtain a stabilized PCE of 26.0% in all-perovskite tandem solar cells. Our strategy provides an avenue to fabricate efficient and stable wide-bandgap subcells for multi-junction photovoltaic devices. This article is protected by copyright. All rights reserved.

15.
Front Genet ; 13: 840961, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401701

RESUMO

Aristolochic acid (AA) is a group of structurally related compounds what have been used to treat various diseases in recent decades. Aristolochic acid I (AAI), an important ingredient, has been associated with tumorigenesis. Recently, some studies indicated that AAI could induce liver injury in mice of different age, but comprehensive mechanisms of AAI-induced differences in liver injury in various age groups have not yet been elucidated. This study aims to evaluate the causal relationship between AAI-induced liver injury and age based on neonatal mice and adult mice. A survival experiment indicated that all neonatal mice survived. Moreover, the adult mice in the high-dose AAI group all died, whereas half of the adult mice in the low-dose AAI group died. In observation experiments, AAI induced more severe liver injury in neonatal mice than adult mice under long-term than short-term exposure. Furthermore, integrated metabolomics and transcriptomics indicated that AAI disturbing steroid hormone biosynthesis, arachidonic acid metabolism, the drug metabolism-cytochrome P450 pathway and glycerophospholipid metabolism induced neonatal mice liver injury. The important role of age in AAI-induced liver injury was illustrated in our study. This study also lays a solid foundation for scientific supervision of AA safety.

16.
Cell Death Discov ; 8(1): 230, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474295

RESUMO

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.

17.
Front Pharmacol ; 13: 861938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462938

RESUMO

Ovarian cancer is the second most common cause of gynecological cancer death in women. It is usually diagnosed late and accompanied by peritoneal metastasis. For ovarian cancer with peritoneal metastasis, intraperitoneal (IP) chemotherapy can maintain a high drug concentration in the abdominal cavity and reduce local and systemic toxicity. Recently, docetaxel (DTX) has shown broad-spectrum antitumor activity against various malignant tumors, including ovarian cancer with peritoneal metastasis. However, DTX has limited clinical applications due to its poor water solubility, predisposition to hypersensitivity, fluid retention, and varying degrees of neurotoxicity. In this study, we prepared methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) micelles loaded with DTX and developed an alternative, less toxic, more effective DTX formulation, without Tween 80, and evaluated its pharmacokinetics in the abdominal cavity and its efficacy in ovarian cancer with peritoneal metastasis. The mean diameter of DTX-mPEG-PDLLA was about 25 nm, and the pharmacokinetics of BALB/c mice via IP showed that the plasma exposure of DTX-mPEG-PDLLA was about four times lower than that of DTX. Importantly, DTX-mPEG-PDLLA was significantly more effective than DTX and prolonged the survival period in a SKOV-3 ovarian cancer peritoneal metastasis model. Moreover, the apoptosis rate was significantly increased in vitro. Based on these findings, it is expected that DTX-mPEG-PDLLA can enhance efficacy against ovarian cancer peritoneal metastasis, while reducing toxic side effects, and has the potential to be used in the clinical treatment of peritoneal metastatic cancer.

18.
Front Genet ; 13: 836431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464850

RESUMO

Type 3 hereditary hemochromatosis (HH) is a rare form of HH characterized by genetic mutation in the TFR2 gene. Clinical features reported in patients with type 3 HH include abnormal liver function, liver fibrosis, cirrhosis, diabetes, hypogonadism, cardiomyopathy, and skin pigmentation. Since its original description in 2000, 33 pathogenic TFR2 mutations associated with HH have been described until now. Here, we first reported a Chinese pedigree of TFR2-related hemochromatosis with a novel compound heterozygous mutation c.1288G > A (p.G430R)/c.960T > A (p.Y320X). Interestingly, different phenotypes were reported although the proband and his sister shared the same gene mutation. This inconsistency between genotypes and phenotypes indicates multifactorial etiology contributing to the development of HH. Our report broadens the mutation spectrum of the TFR2 gene associated with HH.

19.
Front Surg ; 9: 841302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465440

RESUMO

Objective: To establish a simple and practical model for super-microsurgery training using the middle caudal arteries of Kunming mice. Methods: A ⊔-shaped incision was made approximately 1 cm from the root of the tail in the mouse, and the skin, together with the subcutaneous tissue, was turned up into a rectangular shape to the opposite side with exposure of the mouse middle caudal artery and the accompanying veins. The artery was freed for approximately 1 cm in length. The middle caudal artery was cut transversely at the site, and then the severed middle caudal artery was anastomosed end-to-end using 12-0 microsutures in the order of 6, 12, 3, and 9 o'clock with four stitches. Results: The mouse caudal artery had a constant anatomical location accompanied by a vein. The immediate postoperative patency after vascular anastomosis was 100% (15/15) in all mouse models, the postoperative patency was 100% (5/5), 80% (4/5), and 75% (3/4) at 24 h, 3 days, and 1 week postoperatively, respectively. The outer diameter of the mouse middle caudal artery was 0.2 ~ 0.3 (0.22 ± 0.03) mm. The vascular anastomosis time was 6.5 ~ 15 (11.0 ± 2.5) min. Conclusion: The mouse middle caudal artery was superficially located and anatomically constant, making it easy to be located and exposed. The small size of the opening made it suitable for establishing a useful model for training in super-microsurgery vascular anastomoses.

20.
J Chemother ; : 1-14, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380509

RESUMO

Cisplatin (DDP) is first-line management for ovarian cancer (OC). Previous data have suggested that circular RNA_0007841 (circ_0007841) regulates OC progression; however, there is no data on its role in the sensitivity of OC cells to DDP. RNA expression of circ_0007841, microRNA-532-5p (miR-532-5p) and nuclear factor I B (NFIB) was detected by quantitative real-time polymerase chain reaction in OC patient samples and OC cell lines. Protein expression was checked by Western blotting analysis. Cell viability, proliferation, cell apoptotic rate, migration and invasion were investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test and transwell assays, respectively. The interactions among circ_0007841, miR-532-5p and NFIB were identified by a dual-luciferase reporter assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on DDP sensitivity in vivo. Circ_0007841 and NFIB expression were upregulated, whereas miR-532-5p was downregulated in DDP-resistant OC tissues and cells compared with controls. Circ_0007841 silencing improved DDP sensitivity, inhibited cell proliferation, invasion and migration, but induced cell apoptosis in DDP-resistant OC cells. Circ_0007841 acted as a miR-532-5p sponge and regulated DDP resistance and OC cell malignancy through miR-532-5p in DDP-resistant OC cells. Besides, the overexpression of NFIB, a target of miR-532-5p, remitted miR-532-5p-mediated effects in DDP-resistant OC cells. Circ_0007841 depletion conferred DDP sensitivity to DDP-resistant OC cells in vivo. Further, circ_0007841 was secreted from DDP-resistant OC cells through being packaged into exosomes. Circ_0007841 conferred DDP resistance to DDP-resistant OC cells through the miR-532-5p/NFIB axis, suggesting the potential of circ_0007841 as a therapeutic target for OC.

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