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1.
J Biomed Sci ; 29(1): 98, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401329

RESUMO

BACKGROUND: Tumor vascular mimicry is an emerging issue that affects patient survival while having no treatment at the current moment. Despite several factors implicated in vascular mimicry, little is known about stromal factors that modulate tumor microenvironment and shape malignant transformation. CD248, a type-I transmembrane protein dominantly expressed in stromal cells, mediates the interaction between cells and extracellular matrix proteins. CD248 protein expression is associated with the metastatic melanoma phenotype and promotes tumor progression in the stromal cells. This study aimed to explore the cell-autonomous effects of CD248 in melanoma vascular mimicry to aid cancer therapy development. METHODS: Loss-of-function approaches in B16F10 melanoma cells were used to study the cell-autonomous effects of CD248 on cell adhesion, migration, proliferation, and vascular mimicry. A solid-phase binding assay was performed to identify the interaction between CD248 and fibronectin. Horizontal and vertical cell migration assays were performed to analyze cell migration activity, and cell-patterned network formation on Matrigel was used to evaluate vascular mimicry activity. Recombinant CD248 (rCD248) proteins were generated, and whether rCD248 interfered with melanoma CD248 functions was evaluated in vitro. An experimental lung metastasis mouse model was used to investigate the effect of rCD248 treatment in vivo. RESULTS: CD248 protein expression in melanoma cells was increased by a fibroblast-conditioned medium. Knockdown of CD248 expression significantly decreased cell adhesion to fibronectin, cell migration, and vascular mimicry in melanoma cells. The lectin domain of CD248 was directly involved in the interaction between CD248 and fibronectin. Furthermore, rCD248 proteins containing its lectin domain inhibited cell adhesion to fibronectin and slowed down cell migration and vascular mimicry. Treatment with rCD248 protein could reduce pulmonary tumor burden, accompanied by a reduction in vascular mimicry in mice with melanoma lung metastasis. CONCLUSION: CD248 expression in melanoma cells promotes malignant transformation by increasing the activity of cell adhesion, migration, and vascular mimicry, whereas rCD248 protein functions as a molecular decoy interfering with tumor-promoting effects of CD248 in melanoma cells.


Assuntos
Neoplasias Pulmonares , Melanoma , Camundongos , Animais , Fibronectinas , Melanoma/genética , Adesão Celular , Neoplasias Pulmonares/genética , Lectinas/farmacologia , Microambiente Tumoral , Antígenos de Neoplasias/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos CD/farmacologia
2.
J Org Chem ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416373

RESUMO

We report herein the Pd-catalyzed selective ring-opening reaction of cyclopropenones with vinyl epoxides. By using a commercially available Pd2(dba)3·CHCl3-BINAP catalyst, a wide range of conjugated alkadienyl carboxylates could be accessed in good yield and excellent regioselectivity. The new application of zwitterionic π-allyl palladium intermediates has been demonstrated in organic synthesis.

3.
Mol Ecol ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380736

RESUMO

Geographic features and paleoclimatic fluctuations are two classical evolutionary forces for shaping genetic diversification within species. Fine-grain analysis on mechanisms through population demographic processes, however, remains limited. Taking advantage of two recently published reference genomes, we re-sequenced the genomes and examined the evolutionary history of the Moustache toads, a group endemic to East Asia where complex topography and fluctuating paleoclimate are known to have profound impacts on organisms. Moustache toads are likely originated from southeast Yunnan of China and diversified towards the northwestern of Yunnan, as well as central and eastern China. A further exploration on three widespread species (Leptobrachium ailaonicum, L. boringii, and L. liui) using demographic modelling and species distribution modelling revealed that mountains and river valleys in East Asia not only function as geographic barriers, but also provide dispersal corridors and facilitate continuous migration or post-glacial secondary contact among Moustache toad populations. Furthermore, periodic oscillation of effective population size accompanying the fluctuation of historical temperature and population contraction at the Last Glacial Maximum support a widespread impact of Pleistocene climatic changes on species diversification in East Asia. This impact is moderate on populations of L. ailaonicum and L. boringii in the southwestern mountains but is severe on populations of L. liui in the eastern lowland regions of continental East Asia, which is supported by different degrees of change of their effective population sizes. Our findings reveal mechanisms underlying genetic diversification among Moustache toads, and highlight the power of genomic data and demographic modelling for examining complex historical population-level processes and for understanding how geographic and paleoclimatic factors interactively shape current intraspecific diversity.

4.
J Mol Graph Model ; 118: 108370, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36370688

RESUMO

In order to control the magnetic properties and electronic structures of black phosphorene (BP) monolayer, the structures, electronic and magnetic properties of non-metallic elements doped BP monolayer without or with defects including P vacancy (VP) have been studied by density functional theory (DFT). Defective BP appears ferromagnetic metallicity, and the magnetic moment is 0.086 µB. The magnetism mainly comes from the spin polarization of P atoms near the defect point. For non-metallic elements doped intrinsic BP, system doped with B and N shows P-type semiconductor. C doped shows non-magnetic metal properties. Odoped exhibits magnetic P-type semiconductor. Si and S doped shows ferromagnetic metal properties. The magnetism mainly comes from the spin polarization of P atoms near the defect point, and a small part comes from doped atoms. In the case of non-metallic elements doped defective BP, the results show that flaw-b-C and flaw-s-Si exhibit non-magnetic metallic properties. The flaw-b-S shows P-type semiconductor with indirect band gap of 0.712 eV. Other systems exhibit ferromagnetic metallicity, and the magnetism mainly comes from the spin polarization of P atoms near defect point. Non-metallic elements doped BP monolayer without or with point defects can effectively adjust magnetic properties and electronic structures.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36429649

RESUMO

High-quality movement patterns and high levels of mindfulness are thought to be beneficial in preventing sports injuries. Yoga is recommended in the field of athlete rehabilitation. This study investigated the effects of yoga intervention on functional movement patterns and mindfulness in collegiate athletes. It is a quasi-experimental study with a pre/post-test control design. The participants were divided into a yoga group and a control group. A Functional Movement Screen and the Mindful Attention Awareness Scale were used to assess participants' basic movement patterns and mindfulness before and after 12 weeks of yoga intervention (two classes per week, 90 min per class). The results show that the yoga group's FMS scores improved more compared to the control group [F(1,78) = 29.08, p < 0.001, ŋp2 = 0.27], and that the scores for the deep squat (ŋp2 = 0.4), shoulder mobility (ŋp2 = 0.17), and trunk stability pushup (ŋp2 = 0.36) improved substantially. The dysfunctional score ratio for deep squats (χ2 = 18.57, p < 0.001), shoulder mobility (χ2 = 26.90, p < 0.001), trunk stability pushup (χ2 = 17.07, p < 0.001), and rotatory stability (χ2= 38.29, p <0.001) decreased significantly compared with the control group, but there was no significant improvement in asymmetric movement patterns (χ2 = 0.75, p = 0.39). The mindfulness scores in the yoga group significantly exceeded those of the control group [F(1,78) = 13.56, p < 0.001, ŋp2 = 0.15]. These results suggest that yoga intervention can improve functional movement patterns and mindfulness levels, but further evidence is needed to determine whether yoga could positively influence sports injuries.

6.
Cell Genom ; 2(8)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36419822

RESUMO

Intra-tumor heterogeneity (ITH) of human tumors is important for tumor progression, treatment response, and drug resistance. However, the spatial distribution of ITH remains incompletely understood. Here, we present spatial analysis of ITH in lung adenocarcinomas from 147 patients using multi-region mass spectrometry of >5,000 regions, single-cell copy number sequencing of ~2,000 single cells, and cyclic immunofluorescence of >10 million cells. We identified two distinct spatial patterns among tumors, termed clustered and random geographic diversification (GD). These patterns were observed in the same samples using both proteomic and genomic data. The random proteomic GD pattern, which is characterized by decreased cell adhesion and lower levels of tumor-interacting endothelial cells, was significantly associated with increased risk of recurrence or death in two independent patient cohorts. Our study presents comprehensive spatial mapping of ITH in lung adenocarcinoma and provides insights into the mechanisms and clinical consequences of GD.

7.
Medicina (Kaunas) ; 58(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36363480

RESUMO

Background and Objectives: To estimate the clinical outcomes of uniportal and biportal full-endoscopic spine surgery for the treatment of lumbar degenerative disease (LDD), and to provide the latest evidence for clinical selection. Materials and Methods: Relevant literatures published in PubMed, Web of Science, Embase, CNKI, and WanFang Database before 21 November 2021 were searched systematically. Two researchers independently screened the studies, extracted data, and evaluated the risk of bias of the included studies. The systematic review and meta-analysis were performed using the Review Manager software (version 5.4; The Cochrane Collaboration). Results: A total of seven studies were included in this meta-analysis, including 198 patients in a uniportal endoscopy group and 185 patients in a biportal endoscopy group. The results of this meta-analysis demonstrated that the biportal endoscopy group experienced less intraoperative estimated blood loss (WMD = -2.54, 95%CI [-4.48, -0.60], p = 0.01), while the uniportal endoscopy group displayed significantly better recovery results in Visual Analog Scale (VAS) assessments of the back within 3 days of surgery (WMD = 0.69, 95%CI [0.02, 1.37], p = 0.04). However, no significant differences in operation time, length of hospital stay, complication rates, Oswestry Disability Index (ODI) (within 3 months), ODI (last follow-up), VAS for back (within 3 months), VAS for back (last follow-up), and VAS for leg (within 3 days, within 3 months, last follow-up) were identified between the two groups. Conclusions: According to our meta-analysis, patients who underwent the uniportal endoscopic procedure had more significant early postoperative back pain relief than those who underwent the biportal endoscopic procedure. Nevertheless, both surgical techniques are safe and effective.


Assuntos
Endoscopia , Vértebras Lombares , Humanos , Vértebras Lombares/cirurgia , Endoscopia/métodos , Região Lombossacral , Medição da Dor , Duração da Cirurgia , Resultado do Tratamento , Estudos Retrospectivos
8.
Sci Rep ; 12(1): 18564, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329088

RESUMO

Upper airway collapsibility after anaesthesia induction may be associated with unpredictable difficult airway. However, most works on airway anatomy are tended to morphological description before anaesthesia. This study aimed to evaluate the changes of upper airway after anaesthesia induction and using pre-anesthetic ultrasound measurements to predict Difficult Laryngoscopy (DL). We included 104 eligible subjects with complete data, who were performed tracheal intubations under general anaesthesia in the study. The upper airway changes before and after anaesthesia induction were determined by seven neck ultrasound measurements, included as follow: (1) Distance from skin to under surface of Tongue (DT), (2) Thickness of the thickest part of Tongue body (TT), (3) Hyoid Mental Distance (HMD), (4) Depth of Hyoid (DH), (5) Width of Hyoid (WH), (6) Distance from Skin to Epiglottis (DSE), (7) Depth of the anterior combination of the Vocal Cords (DVC). DL was evaluated with Cormack-Lehane (CL). Data regarding HMD [from 45.3 (42.4-48.5) to 41.1 (38.5-44.9) mm], DH [from 8.7 (6.6-10.9) to 7.0 (5.3-9.1) mm], DSE [from 20.1 (16.6-22.5) to 19.5 (16.5-21.6) mm] and the DVC [from 7.1 (5.7-8.3) to 6.8 (5.7-7.9) mm] were decreased (P < 0.05), while the DT [from 15.9 (13.1-18.4) to 17.4 (14.5-19.8) mm] was increased (P > 0.05) after anaesthesia induction. Additionally, when cut-off value of DSE was 21.25 mm before anaesthesia, it may be better predicted to DL [sensitivity 80.0% (95% CI: 60.7-91.6%) and specificity 83.8% (95% CI: 73.0-91.0%)]. The upper airway after induction showed the propensity of collapsibility by ultrasound measurements. Compared with other indicators, the DSE assessed by ultrasound might be considered to a valuable predictor of DL.Trial registration: The study was registered in ClinicalTrials.gov on 23th Jan 2019, ChiCTR1900021123.


Assuntos
Laringoscopia , Laringe , Humanos , Intubação Intratraqueal , Laringe/diagnóstico por imagem , Anestesia Geral , Epiglote
9.
Pain Physician ; 25(7): E917-E930, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36288578

RESUMO

BACKGROUND: The optimal analgesia for video-assisted thoracoscopic surgery (VATS) is still unknown. OBJECTIVES: Our aim was to conduct a network meta-analysis and systematic review to compare the efficacy of different analgesic strategies in VATS. STUDY DESIGN: Bayesian network meta-analysis. METHODS: We searched PubMed, Embase, Medline, Springer, Google Scholar, and Web of Science to evaluate all relevant randomized controlled trials that investigated the analgesic effects of different regional analgesia methods for VATS published through July 2021. After a comprehensive search of electronic databases, the following methods were identified: epidural analgesia (EA), local anesthetics (LA), superficial serratus anterior plane block (SSAPB), deep serratus anterior plane block (DSAPB), erector spinae plane block (ESPB), paravertebral block (PVB), and intercostal nerve block (ICNB). Primary outcomes were the visual analog scale score at rest, at 2 hours, 6 hours and 24 hours postoperatively. The secondary outcomes were postoperative analgesic consumption, incidence of nausea and emesis, and pruritus. RESULT: Overall, 35 trials met our inclusion criteria. EA and PVB were relatively more advantageous in terms of analgesic effect at 2 hours and 6 hours postoperatively; the EA group was superior to the DSAPB, ESPB, and ICNB groups at 24 hours postoperatively. EA was found to be superior to other analgesia techniques for 24 hour postoperative analgesic consumption., PVB showed advantages in reducing postoperative nausea, emesis, and pruritus. LIMITATIONS: Different concentrations and volumes of local anesthetics might affect the analgesic effects of the various analgesia techniques. CONCLUSION: EA and PVB have certain advantages in analgesia, but the incidence of postoperative pruritus after EA is higher. At the same time, considering the risk of coagulation and puncture complications, PVB may be a better choice.


Assuntos
Analgesia Epidural , Cirurgia Torácica Vídeoassistida , Humanos , Cirurgia Torácica Vídeoassistida/métodos , Dor Pós-Operatória/tratamento farmacológico , Anestésicos Locais , Metanálise em Rede , Teorema de Bayes , Náusea e Vômito Pós-Operatórios , Analgésicos , Prurido
10.
Artigo em Inglês | MEDLINE | ID: mdl-36193150

RESUMO

The efficacy of massage therapy in the treatment of children with autism spectrum disorder (ASD) remains unclear. This study systematically reviewed the impact of massage therapy on children with ASD according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) declaration guidelines. A literature search of the PubMed, Web of Science, Science Direct, Scopus, Google Scholar, and China National Knowledge Infrastructure (CNKI) electronic databases from inception to December 20, 2020, was conducted using the term "autistic/autism" along with one of the following terms, "massages," and "Tui na." The risk of bias was assessed using the Cochrane risk of bias Tool. Eight randomized controlled trials examining the impact of massage on children with ASD were included. Interventions combining Qigong massage or Tui na with the control group treatments from once a day to twice a week, for a duration of 15-30 mins, and lasting for six weeks to five months were the main interventions. All reviewed studies reported significant improvement in children with ASD who received massage, especially in the sensory domain, and that massage in combination with control treatment was superior to control treatment alone. However, the overall quality of the available studies is poor with a high degree of heterogeneity. The majority of studies showed a high risk of bias with poor study design, inconsistency in massage protocols, and subjective outcome measures. Assessment bias was a common weakness of these studies. Therefore, there is insufficient evidence to conclude that massage is effective for ASD. Future studies should include large sample sizes, incorporate double-blind designs, employ appropriate outcome measures, and allow for long observation and follow-up periods. Furthermore, consensus must be reached on standardized treatments and additional therapies in order to provide better quality evidence for the treatment of ASD.

11.
Chaos ; 32(9): 093145, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36182381

RESUMO

Heart disease is the leading cause of death and is often accompanied by cardiac fibrillation. Defibrillation using the virtual electrode effects is a promising alternative compared to using the high-voltage electric shock in the clinic. Our earlier works [S. L. Murphy, K. D. Kochanek, J. Xu, and E. Arias, NCHS Data Brief 427 (2021); R. A. Gray, A. M. Pertsov, and J. Jalife, Nature 392, 75-78 (1998); F. X. Witkowski, L. J. Leon, P. A. Penkoske, W. R. Giles, M. L. Spano, W. L. Ditto, and A. T. Winfree, Nature 392, 78-82 (1998); M. Santini, C. Pandozi, G. Altamura, G. Gentilucci, M. Villani, M. C. Scianaro, A. Castro, F. Ammirati, and B. Magris, J. Interv. Card. Electrophysiol. 3, 45-51 (1999).] prove that, compared with other external electric fields, a low voltage circularly polarized electric field is more efficient in turning non-excitable defects in cardiac tissue into virtual electrodes. It, therefore, needs lower voltage to stimulate the excitation waves and causes less harm to reset the spiral turbulence of cardiac excitation for defibrillation. In this paper, we investigate the virtual electrode effect of multiple defects by the circularly polarized electric field for the removal of spiral turbulence. Considering different shapes, sizes, and distributions of multiple defects, we reveal the phase locking of stimulated excitations around multiple virtual electrodes. Furthermore, the circularly polarized electric field parameters are optimized to remove the spiral turbulence.


Assuntos
Arritmias Cardíacas , Eletricidade , Simulação por Computador , Cardioversão Elétrica , Eletrodos , Coração , Humanos
12.
World J Gastrointest Oncol ; 14(9): 1675-1688, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36187390

RESUMO

BACKGROUND: Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers (CRC). Human six-transmembrane epithelial antigen of the prostate (STEAP) proteins have been recognized and utilized as promising targets for cell- and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated. AIM: To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas. METHODS: The expression level of STEAPs in CRC was evaluated using various open-resource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immune-related biomarkers, such as immune infiltration. Immunohistochemical (IHC) experiments were subsequently performed to verify the database conclusions. RESULTS: The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However, STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees. CONCLUSION: Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.

13.
J Nucl Med ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36215571

RESUMO

PET imaging targeting fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of the 68Ga-FAP-2286 to detect the primary and metastatic lesions in patients with various types of cancer, compared with 18F-fluorodeoxyglucose (FDG) and 68Ga-FAP-2286. Methods: Sixty four patients with 15 types of cancer underwent 68Ga-FAP-2286 PET/ CT for initial assessment or recurrence detection. For comparative purposes, 63 patients underwent paired 68Ga-FAP-2286 and 18F-FDG PET/CT, and 19 patients underwent paired 68Ga-FAP-2286 and 68Ga-FAPI-46 PET/CT imaging. Lesion uptake was quantified as the maximum standardized uptake value (SUVmax) and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUVmax values, and McNemar's test was used to compare the lesion detectability between PET modalities. Results: The uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary tumors (median SUVmax: 11.1 vs. 6.9, P < 0.001), lymph node metastases (median SUVmax: 10.6 vs. 6.2, P < 0.001), and distant metastases, resulted in improved image contrast and higher lesion detectability. All primary tumors (46/46) were clearly visualized by 68Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized via 18F-FDG PET/CT. The lesion detection rate of 68Ga-FAP-2286 PET/CT was superior to that of 18F-FDG PET/CT for involved lymph nodes (98 % [105/107] vs. 85 % [91/107], P = 0.001), bone and visceral metastases (95 % [162/171] vs. 67 % [114/171], P < 0.001). 68Ga-FAP-2286 yielded similar tumor uptake and lesion detection rates as compared with 68Ga-FAPI-46 in a subcohort of 19 patients. Conclusion: 68Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to 18F-FDG for the cancer types that exhibit low-to-moderate uptake of 18F-FDG, which including gastric, pancreatic, and liver cancers. In addition, 68Ga-FAP-2286 and 68Ga-FAPI-46 yielded comparable clinical results.

14.
Int J Hyg Environ Health ; 246: 114049, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36279789

RESUMO

The incidence of thyroid cancer (TC) has increased rapidly in last decades. Multiple trace elements in the external environment have important effects with thyroid function. However, the evidence for these on TC risk were rarely reported. A total of 585 newly diagnosed TC patients and 585 healthy controls were included in this study, and 14 urinary elements were measured to explain the fixed-exposure effect on TC risk. Conditional logistic regressions were used to reflect the multi-element associations, and Bayesian kernel machine regression (BKMR) was applied to show the tendency of mixed effects. Furthermore, the interaction effects were examined by Generalized linear model (GLM). The levels of lithium (Li), cobalt (Co), strontium (Sr), zinc (Zn) and copper (Cu) had negative effects with TC risk, nevertheless lead (Pb), arsenic (As) and chromide (Cr) showed positive effects. The BKMR and GLM models reflected the effect fluctuations of different elements, and there was a slight interaction effects between Li and Cr, Co, Zn and Pb. Further study is required to confirm these results in the future.


Assuntos
Neoplasias da Glândula Tireoide , Oligoelementos , Adulto , Humanos , Estudos de Casos e Controles , Teorema de Bayes , Chumbo , Neoplasias da Glândula Tireoide/epidemiologia , China/epidemiologia
15.
Hum Brain Mapp ; 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36308417

RESUMO

Blood and cerebrospinal fluid (CSF) pulse and flow throughout the brain, driven by the cardiac cycle. These fluid dynamics, which are essential to healthy brain function, are characterized by several noninvasive magnetic resonance imaging (MRI) methods. Recent developments in fast MRI, specifically simultaneous multislice acquisition methods, provide a new opportunity to rapidly and broadly assess cardiac-driven flow, including CSF spaces, surface vessels and parenchymal vessels. We use these techniques to assess blood and CSF flow dynamics in brief (3.5 min) scans on a conventional 3 T MRI scanner in five subjects. Cardiac pulses are measured with a photoplethysmography (PPG) on the index finger, along with functional MRI (fMRI) signals in the brain. We, retrospectively, align the fMRI signals to the heartbeat. Highly reliable cardiac-gated fMRI temporal signals are observed in CSF and blood on the timescale of one heartbeat (test-retest reliability within subjects R2  > 50%). In blood vessels, a local minimum is observed following systole. In CSF spaces, the ventricles and subarachnoid spaces have a local maximum following systole instead. Slower resting-state scans with slice timing, retrospectively, aligned to the cardiac pulse, reveal similar cardiac-gated responses. The cardiac-gated measurements estimate the amplitude and phase of fMRI pulsations in the CSF relative to those in the arteries, an estimate of the local intracranial impedance. Cardiac aligned fMRI signals can provide new insights about fluid dynamics or diagnostics for diseases where these dynamics are important.

16.
World J Pediatr ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36306051

RESUMO

BACKGROUND: INTERGROWTH-21st Newborn Cross-Sectional Study (NCSS) charts were established and recommended for global application. However, whether one international reference is appropriate for all populations is still unclear. We aim to compare the updated Chinese birth size charts by gestational age with INTERGROWTH-21st NCSS charts. METHODS: A cross-sectional survey was carried out, and the birth weight, length and head circumference of 24,375 infants born after uncomplicated pregnancies at gestational age ranging from 24+0 to 42+6 weeks were measured in 13 cities in China from 2015 to 2018. Growth charts were constructed. The measurements of all these infants were evaluated by the methods of calculating their Z scores using the INTERGROWTH-21st standards. The prevalence of small for gestational age (SGA) and large for gestational age (LGA) based on birth weight was analyzed using Chinese charts and INTERGROWTH-21st charts. RESULTS: The mean Z scores were 0.10 for birth weight, 0.35 for length and - 0.02 for head circumference. Compared to the INTERGROWTH-21st charts, the Chinese birth weight percentile curves were higher except for the 90th percentile at 29-37 weeks gestational age, and the length percentile curves were higher after 33 weeks gestational age, while the 10th percentile of the head circumference was lower and the other percentiles were similar. The prevalence of SGA was 10.1% [95% confidence interval (CI) = 9.7%-10.5%] using the Chinese birth weight chart and 6.5% (95% CI = 6.2%-6.8%) using the INTERGROWTH-21st birth weight chart. The prevalence of LGA was 9.9% (95% CI = 9.5%-10.2%) and 8.2% (95% CI = 7.9%-8.6%) using the Chinese and INTERGROWTH-21st birth weight charts, respectively. CONCLUSIONS: Chinese birth size charts based on infants born after uncomplicated pregnancies were different from the INTERGROWTH-21st charts. Differences in the classification of newborns by the two charts should receive attention, and whether the application of INTERGROWTH-21st in Chinese newborns will lead to misclassification needs to be validated in future clinical practice.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36222855

RESUMO

BACKGROUND: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. METHODS: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann-Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan-Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. RESULTS: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16-29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13-15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55-18.79, P = 0.001). CONCLUSION: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed.

18.
Acta Biomater ; 153: 540-556, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36162762

RESUMO

The biggest application bottleneck of antimicrobial peptides (AMPs) is the low oral bioavailability caused by the poor stability of digestive enzymes in the gastrointestinal tract. However, the research methods and evaluation criteria of available studies about anti-proteolytic strategies are not uniform and far from the actual environment in vivo. Here, we developed a research system and evaluation criteria for proteolytic resistance and systematically evaluated the effectiveness of different strategies for improving the protease stability of AMPs on the same platform for the first time. After a comprehensive analysis, Dab modification is identified as the most effective strategy to improve the trypsin stability of AMPs. By further modulating the proteolytic resistance optimization motif (DabW)n, U1-2WD is obtained with ideal stability and antimicrobial properties in vivo and in vitro. Notably, U1-2WD has a unique antibacterial mechanism, which forms amorphous aggregates in the bacteria environment to trigger the agglutination of bacterial cells to prevent bacterial escape. It then kills bacteria by disrupting bacterial membranes and inhibiting bacterial energy metabolism. Overall, our work has led to a new understanding of the effectiveness of proteolytic resistance strategies and accelerated the development of anti-proteolytic AMPs to combat multidrug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: We developed research system and evaluation criteria for proteolytic resistance and systematically evaluated the effectiveness of different strategies for improving protease stability of AMPs on the same platform for the first time. we found effective strategies to resist trypsin hydrolysis: modification with backbone (ß-Arg), D-enantiomer (D-Arg) and L-2,4-diaminobutanoic acid (Dab). Further, the proteolytic resistance optimization motif (DabW)n was designed. When n=3, derivative U1-2WD was obtained with desirable stability and antimicrobial properties in vivo and in vitro. Notably, U1-2WD has a unique antibacterial mechanism, which can self-aggregate into amorphous aggregates in the bacteria environment to mediate the agglutination and sedimentation of bacterial cells to prevent bacterial escape, and then kill bacteria by destroying bacterial membranes and inhibiting bacterial energy metabolism.


Assuntos
Anti-Infecciosos , Peptídeos Catiônicos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Tripsina/farmacologia , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Peptídeo Hidrolases/farmacologia , Aglutinação , Testes de Sensibilidade Microbiana
19.
Plant Physiol Biochem ; 191: 20-33, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174283

RESUMO

Tartary buckwheat [Fagopyrum tataricum (L.) Gaertn.] is a pseudocereal with strongly abiotic resistance. NACs, one of the largest plant-specific transcription factors (TFs), are involved in various stress responses. However, the characteristics and regulatory mechanisms of NAC TFs remain unclarified clearly in Tartary buckwheat (TB). In this study, it validated that salt, drought, and abscisic acid (ABA) stress significantly up-regulated the expression of NAC TF gene FtNAC31. Its coding protein has a C-terminal transactivated domain and localized in the nucleus, suggesting that FtNAC31 might play a transcriptional activation role in TB. Notably, overexpression of FtNAC31 lowered the seed germination rate upon ABA treatment and enhanced the tolerance to salt and drought stress in transgenetic Arabidopsis. Furthermore, under various stresses, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in FtNAC31 overexpressed lines exhibited a sharp increase trend. Meanwhile, the expression levels of several stress-associated genes including RD29A, RD29B, RD22, DREB2B, NCED3, and POD1, were dramatically upregulated in lines overexpressing FtNAC31. Altogether, overproduction of FtNAC31 could enhance the resistance to salt and drought stresses in transgenic Arabidopsis, which most likely functioned in an ABA-dependent way.


Assuntos
Arabidopsis , Fagopyrum , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Catalase/metabolismo , Secas , Fagopyrum/genética , Fagopyrum/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Front Vet Sci ; 9: 986824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061114

RESUMO

Integrative conjugative elements (ICEs) are important carriers for disseminating resistance genes. We have previously reported a novel element ICEHpa1 carrying seven antibiotic resistance genes, which could be self-transmissible relying on the novel T4SS. To identify novel ICEHpa1 variants from 211 strains and novel T4SS encoded in ICEHpa1, and to explore the relationships in these ICEs, four complete sequences of ICEs were identified by WGS analysis and antimicrobial susceptibility testing was determined by broth microdilution. In addition, a comparative analysis of these ICEs was conducted with bioinformatic tools, and the transfer abilities of these ICEs were confirmed by conjugation. Four ICEHpa1 variants ICEGpa1818, ICEGpa1808, ICEGpa1807, and ICEGpa1815 with different resistance gene profiles were characterized, and their hosts showed different resistance spectrums. All ICEs shared the same backbone and were inserted into the tRNALeu site, and all resistance regions were inserted into the same target site between the accessory and integration regions. This study analyzed complete sequences of ICEs from the ICEHpa1 family and identified novel T4SS and insertion element ISGpa2. Diverse resistance genes extensively exist in these ICEs, serving as a reservoir for resistance genes and facilitating their dissemination.

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