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1.
BMC Bioinformatics ; 24(1): 238, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280525

RESUMO

Lung squamous cell carcinoma (LUSC) is associated with a worse prognosis than other histological subtypes of non-small cell lung cancer. Due to the vital role of CD8+ T cells in anti-tumor immunity, the characterization of CD8+ T cell infiltration-related (CTLIR) gene signature in LUSC is worthy of in-depth exploration. In our study, tumor tissues of LUSC patients from Renmin Hospital of Wuhan University were stained by multiplex immunohistochemistry to evaluate the density of infiltrated CD8+ T cells and explore the correlation with immunotherapy response. We found that the proportion of LUSC patients who responded to immunotherapy was higher in the high density of CD8+ T cell infiltration group than in the low density of CD8+ T cell infiltration group. Subsequently, we collected bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) database. The abundance of infiltrating immune cells in LUSC patients was analyzed by using CIBERSORT algorithm, and weighted correlation network analysis was performed to identify the co-expressed gene modules related to CD8+ T cells. We then developed a prognostic gene signature based on CD8+ T cell co-expressed genes and calculated the CTLIR risk score, which stratified LUSC patients into high-risk and low-risk groups. With univariate and multivariate analyses, the gene signature was identified as an independent prognostic factor in LUSC patients. The overall survival of LUSC patients in the high-risk group was significantly shorter than that of the low-risk group in the TCGA cohort, which was validated in Gene Expression Omnibus datasets. We analyzed immune cell infiltration in the tumor microenviroment and found fewer CD8+ T cells and more regulatory T cell infiltration in the high-risk group, which is characterized as an immunosuppressive phenotype. Furthermore, the LUSC patients in the high-risk group were predicted to have a better response to immunotherapy than those in the low-risk group when treated with PD-1 and CTLA4 inhibitors. In conclusion, we performed a comprehensive molecular analysis of the CTLIR gene signature in LUSC and constructed a risk model for LUSC patients to predict prognosis and immunotherapy response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Linfócitos T CD8-Positivos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Imunoterapia , Pulmão
2.
New Phytol ; 239(5): 1740-1753, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37301984

RESUMO

Pollen tubes have dynamic tubular vacuoles. Functional loss of AP-3, a regulator of one vacuolar trafficking route, reduces pollen tube growth. However, the role of canonical Rab5 GTPases that are responsible for two other vacuolar trafficking routes in Arabidopsis pollen tubes is obscure. By using genomic editing, confocal microscopy, pollen tube growth assays, and transmission electron microscopy, we demonstrate that functional loss of canonical Rab5s in Arabidopsis, RHA1 and ARA7, causes the failure of pollen tubes to grow through style and thus impairs male transmission. Functional loss of canonical Rab5s compromises vacuolar trafficking of tonoplast proteins, vacuolar biogenesis, and turgor regulation. However, rha1;ara7 pollen tubes are comparable to those of wild-type in growing through narrow passages by microfluidic assays. We demonstrate that functional loss of canonical Rab5s compromises endocytic and secretory trafficking at the plasma membrane (PM), whereas the targeting of PM-associated ATPases is largely unaffected. Despite that, rha1;ara7 pollen tubes contain a reduced cytosolic pH and disrupted actin microfilaments, correlating with the mis-targeting of vacuolar ATPases (VHA). These results imply a key role of vacuoles in maintaining cytoplasmic proton homeostasis and in pollen tube penetrative growth through style.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Tubo Polínico , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Adenosina Trifosfatases/metabolismo
3.
J Exp Bot ; 74(3): 1123-1139, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36462194

RESUMO

Most orchids have high ornamental value with long-lived flowers. However, the mechanisms by which orchids maintain floral longevity are poorly understood. Here, we hypothesized that floral longevity in Dendrobium is maintained by high resource investment and complementary water and nutrient utilization in different structural units of the perianth. To test this hypothesis, we determined which water- and nutrient-related traits are correlated with flower longevity in 23 Dendrobium species or cultivars, and examined variations of the related traits during flower development of one long-lived cultivar. We found that floral longevity was correlated with dry mass per unit area of perianths and total flower biomass, which indicates that maintaining floral longevity requires increased resource investment. During development of long-lived flowers, labella showed a high capacity for water storage and nutrient reutilization, which could partly remedy high water demand and biomass investment. Sepals and petals, in contrast, had stronger desiccation avoidance and higher metabolic activity with lower biomass investment. These findings indicate that Dendrobium flowers maintain longevity by complementary water and nutrient utilization strategies in the sepals, petals and labella, with labella consuming more water and nutrients to extend flower display, and sepals and petals using a more conservative strategy.


Assuntos
Dendrobium , Água , Água/metabolismo , Longevidade , Reprodução , Flores
4.
J Pineal Res ; 74(4): e12859, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36732085

RESUMO

Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R-like ER kinase-eukaryotic initiation factor 2α-C/EBP-homologous protein, inositol-requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress-induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER-phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER-phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER-phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER-phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well-designed randomized controlled trials must be carried out to further investigate its clinical effects.


Assuntos
Medula Cervical , Melatonina , Ratos , Animais , Melatonina/farmacologia , Melatonina/metabolismo , Estresse do Retículo Endoplasmático , Apoptose , Neurônios/metabolismo , Retículo Endoplasmático/metabolismo , Homeostase
5.
Cell Biol Toxicol ; 39(3): 907-928, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35028790

RESUMO

Cervical spondylotic myelopathy (CSM) is a clinically symptomatic entity arising from the spinal cord compression by degenerative diseases. Although endoplasmic reticulum (ER) stress has been commonly observed in several neurodegenerative diseases, the relationship between ER stress and CSM remains unknown. Shikonin is known to protect PC12 by inhibiting apoptosis in vitro. This study hypothesised that ER stress was vital in neuronal apoptosis in CSM. Shikonin might inhibit such responses by regulating ER stress through the protein kinase-like ER kinase-eukaryotic translation initiation factor 2 α-subunit-C/EBP homologous protein (PERK-eIF2α-CHOP) signalling pathway. Thus, the aim of this study was evaluating the neuroprotective effect of shikonin in rats with double-level chronic cervical cord compression, as well as primary rat cortical neurons with glutamate-induced neurotoxicity. The result showed that ER stress-related upregulation of PERK-eIF2α-CHOP resulted in rat neuronal apoptosis after chronic cervical cord compression; then, shikonin promoted motor recovery and inhibited neuronal apoptosis by attenuating PERK-eIF2α-CHOP and prevented Bax translocation from cytoplasm to mitochondrion induced by CHOP of neurons in rats with chronic compression. Also, it was found that shikonin could protect rat primary cortical neuron against glutamate toxicity by regulating ER stress through the PERK-eIF2α-CHOP pathway in vitro. In conclusion, shikonin might inhibit neuronal apoptosis by regulating ER stress through attenuating the activation of PERK-eIF2α-CHOP.


Assuntos
Medula Cervical , Compressão da Medula Espinal , Ratos , Animais , Compressão da Medula Espinal/tratamento farmacológico , Medula Cervical/metabolismo , Estresse do Retículo Endoplasmático , Apoptose , Fator de Iniciação 2 em Eucariotos/metabolismo , eIF-2 Quinase/metabolismo
6.
Nutr Neurosci ; : 1-17, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950873

RESUMO

BACKGROUND: To comprehensively assess the neurologic recovery potential of chondroitinase ABC (ChABC) in rats after spinal cord injury (SCI). METHODS: The PubMed, Embase, ScienceDirect, Web of Science, and China National Knowledge Infrastructure databases were searched for animal experiments that evaluated the use of ChABC in the treatment of SCI up to November 2022. Studies reporting neurological function using the Basso, Beattie, and Bresnahan (BBB) scale, as well as assessments of cavity area, lesion area, and glial fibrillary acidic protein (GFAP) levels, were included in the analysis. RESULTS: A total of 46 studies were ultimately selected for inclusion. The results of the study showed that rats with SCI that received ChABC therapy exhibited a significant improvement in locomotor function after 7 days compared with controls (32 studies, weighted mean difference (WMD) = 0.58, [0.33, 0.83], p < 0.00001). Furthermore, the benefits of ChABC therapy were maintained for up to 28 days according to BBB scale. The lesion area was reduced by ChABC (5 studies, WMD = -20.94, [-28.42, -13.46], p < 0.00001). Meanwhile, GFAP levels were reduced in the ChABC treatment group (8 studies, WMD = -29.15, [-41.57, -16.72], p < 0.00001). Cavity area is not statistically significant. The subgroup analysis recommended that a single injection of 10 µL (8 studies, WMD = 2.82, [1.99, 3.65], p < 0.00001) or 20 U/mL (4 studies, WMD = 2.21, [0.73, 3.70], p = 0.003) had a better effect on improving the function. The funnel plot of the BBB scale was found to be essentially symmetrical, indicating a low risk of publication bias. CONCLUSIONS: This systematic review and meta-analysis has indicated that ChABC could improve functional recovery in rats after SCI.

7.
Nutr Neurosci ; : 1-13, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37691351

RESUMO

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

8.
Sleep Breath ; 27(2): 421-429, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35624400

RESUMO

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by recurrent upper airway disturbances during sleep leading to episodes of hypopnea or apnea, followed by hypoxemia and subsequent reoxygenation. It is believed that this reoxygenation/reperfusion stage leads to oxidative stress, which then leads to inflammation and cardiovascular diseases. The treatments of patient with OSAHS include surgical and non-surgical therapies with various side effects and common complaints. Therefore, it is important to develop a new, safe, and effective therapeutic treatment. As a small-molecule multifunctional protein, thioredoxin (TRX) has antioxidant and redox regulatory functions at the active site Cys-Gly-Pro. TRX prevents inflammation by suppressing the production of pro-inflammatory cytokines rather than suppressing the immune response. METHODS: We review the papers on the pathophysiological process of OSAHS and the antioxidative and anti-inflammatory effects of TRX. RESULTS: TRX may play a role in OSAHS by scavenging ROS, blocking the production of inflammatory cytokines, inhibiting the migration and activation of neutrophils, and controlling the activation of ROS-dependent inflammatory signals by regulating the redox state of intracellular target particles. Furthermore, TRX regulates the synthesis, stability, and activity of hypoxia-inducible factor 1 (HIF-1). TRX also has an inhibitory effect on endoplasmic reticulum- and mitochondria-induced apoptosis by regulating the expression of BAX, BCL2, p53, and ASK1. CONCLUSION: Understanding the function of TRX may be useful for the treatment of OSAHS.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Espécies Reativas de Oxigênio/metabolismo , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/metabolismo , Antioxidantes , Citocinas , Inflamação , Tiorredoxinas
9.
J Orthop Sci ; 28(5): 984-991, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36137918

RESUMO

BACKGROUND: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is a reliable and sensitive measure of disability to determine functional status and evaluate curative effects in low back pain, it has now been cross-cultural translated into many other languages and adapted for use in different countries. We aim to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the JOABPEQ. METHODS: Studies related to cross-cultural adaptation of the JOABPEQ in a specific language/culture were searched in PubMed, Embase, CINAHL, SciELO, PsycINFO, SinoMed, and Web of Science from their inception to March 2022. The Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Consensus-based Standards for the Selection of Health Status Measurement Instruments guideline were used for evaluation. RESULTS: Nine different versions of cross-cultural JOABPEQ adaptations in 8 different languages/cultures were included. The adaptation process was not strictly performed, such as standard forward translation and expert committee review were rarely reported. Content validity (8/9), floor and ceiling effects (3/9), reliability (4/9), and interpretability (6/9) were assessed in most of the adaptations, while agreement (2/9), responsiveness (2/9), and the internal consistency (2/9) were not. JOABPEQ can replace functional and quality of life score to reduce the burden of scientific research. CONCLUSION: We recommend Persian-Iranian, simplified Chinese-Chinese Mandarin, Thai and Gunaydin G's Turkish adaptations for application. The numerical pain rating scale/visual analogue scale in low back pain and lower extremities, as well as numbness in lower extremities could not be neglected in JOABPEQ adaptations.


Assuntos
Comparação Transcultural , Dor Lombar , Ortopedia , Humanos , Dor nas Costas , Avaliação da Deficiência , Dor Lombar/diagnóstico , Psicometria/métodos , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Clin Anat ; 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37596889

RESUMO

To investigate the computed tomography (CT) image characteristics, adjacent tissues, and related measurement indices of the sternal foramina and provide an anatomical basis for the safety of minimally invasive sternum surgery. The data from 2500 thoracic multi-slice computed tomography (MSCT) cases from January 2020 to June 2021 were analyzed retrospectively. The number and location of the sternal foramina and adjacent tissues (mediastinal adipose tissue, lung, pericardium) were observed. The size of the sternal foramina, CT value of the tissue inside the foramina, subcutaneous adipose tissue thickness, distance from skin to lung, distance from skin to the pericardium, and manubrio-foraminal distance were measured. Sex differences were compared for each indicator performed. The incidence of sternal foramina was 4.44% (111/2500), with 83 males and 28 females. All sternal foramina were located at the mesosternum's fourth to sixth costal cartilage level. The transverse diameter of the sternal foramina was (0.60 ± 0.29) cm, and the vertical diameter was (0.68 ± 0.39) cm, which was greater in males than females (p > 0.01). The CT value of the tissue in the sternal foramina was (-77.05 ± 32.26) Hu, and there was no statistical difference between male and female patients (t = -1.780, p = 0.078). The adjacent tissues of the sternal foramina were only adjacent to adipose tissue in 41 cases (36.94%), pericardium in 18 patients (16.22%), lung tissue in 37 cases (33.33%), and both kinds of tissue in 15 cases (13.51%). The sternal foramina were not adjacent to the left lung in the female patients. In the sternal foramina region, the thickness of subcutaneous adipose tissue was (1.13 ± 0.51) cm, the distance from skin to lung was (1.86 ± 0.57) cm, the distance from skin to pericardium was (3.07 ± 0.72) cm, the manubrio-foraminal distance was (12.68 ± 1.31) cm, which was significantly greater in males than in females (p < 0.05). The sternal foramina are closely related to the heart and lungs. The size and location of sternal foramina, the thickness of subcutaneous adipose tissue, and the distance from skin to heart and lung are all crucial factors in evaluating the safety of sternal puncture biopsy.

11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 357-360, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36949698

RESUMO

Objective: To analyze the screening value of osteoporosis self-screening tool for Asia (OSTA) and body mass index (BMI) for osteoporosis (OP) in middle-aged and elderly Tibetan population in the Tibetan region. Methods: Data on demographic information, bone mineral density (BMD), and other information of 627 middle-aged and elderly people were collected. Analysis of the correlation between OSTA index, BMI and BMD, and receiver operating characteristic (ROC) curve was performed to evaluate the OP screening effects. Results: OSTA index and BMI were correlated with BMD in both female and male populations ( P<0.05). In both male and female populations, OSTA index screening results for OP yielded higher area under the curve ( AUC) than BMI did, with the AUC for female OSTA index being 0.886 and that for female BMI being 0.785, while that for male OSTA index being 0.957 and that for male BMI being 0.834. When comparing the different age groups, the AUC of OSTA index and BMI of the middle-age group was higher than those of the quasi-elderly group and the elderly group, with the AUC of OSTA index and BMI of the middle-age being 0.939 and 0.858, those of the quasi-elderly group being 0.860 and 0.813, and those of the elderly group being 0.750 and 0.650, respectively. When the optimal cut-off value of diagnosis with OSTA index was -2.20, the sensitivity and specificity were both 100%. When the optimal cut-off value for diagnosis with BMI was 17.512 kg/m2, the sensitivity and specificity were both 100%. Conclusion: OSTA index and BMI have different OP screening effects in different middle-aged and elderly Tibetan populations, and OSTA index shows better effects for OP screening than BMI does.


Assuntos
Osteoporose , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Absorciometria de Fóton/métodos , Índice de Massa Corporal , Densidade Óssea , Programas de Rastreamento/métodos , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Medição de Risco/métodos , Autoavaliação (Psicologia) , Tibet , População do Leste Asiático
12.
Opt Lett ; 47(15): 3944-3947, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913354

RESUMO

Whispering-gallery-mode (WGM) microcavities have shown significant applications in nanoparticle sensing for environmental monitoring and biological analysis. However, the enhancement of detection resolution often calls for active cavities or elaborate structural designs, leading to an increase of fabrication complexity and cost. Herein, heterodyne amplification is implemented in WGM microsensors based on backscattering detection mechanism. By interfering with an exotic reference laser, the reflecting light backscattered by perturbation targets can be strongly enlarged, yielding an easy-to-resolve and consequently sensitive microsensor. The dependence of detection laser frequency has also been characterized with the assistance of optothermal dynamics. We show that exploiting heterodyne interferometry boosts the detection of weak signals in microresonator systems and provides a fertile ground for optical microsensor development.


Assuntos
Nanopartículas
13.
Liver Int ; 42(3): 682-695, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34743403

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2. METHODS: Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RESULTS: Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo. CONCLUSION: Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Hepáticas/patologia , Camundongos , MicroRNAs/metabolismo , RNA Circular/genética
14.
J Org Chem ; 87(5): 3661-3667, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35029390

RESUMO

A one-pot strategy for α-keto amide bond formation have been developed by using ynamides as coupling reagents under extremely mild reaction conditions. Diversely structural α-ketoamides were afforded in up to 98% yield for 36 examples. This reaction features advantages such as practical coupling procedure, wide functional group tolerance, and extremely mild conditions and has potential applications in synthetic and medicinal chemistry.


Assuntos
Aminas , Cetoácidos , Aminas/química , Indicadores e Reagentes , Oxirredução
15.
Ecotoxicol Environ Saf ; 248: 114303, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403304

RESUMO

Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46-1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl2-low) and 1.5 (ZnCl2-high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl2-low, 0.48 (∼0.51); ZnCl2-high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid ß-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish.


Assuntos
Transtornos Cronobiológicos , Peixe-Zebra , Animais , Zinco/toxicidade , Peptídeos beta-Amiloides , Encéfalo , Agressão , Fígado
16.
BMC Biol ; 19(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088313

RESUMO

BACKGROUND: The vacuole/lysosome is the final destination of autophagic pathways, but can also itself be degraded in whole or in part by selective macroautophagic or microautophagic processes. Diverse molecular mechanisms are involved in these processes, the characterization of which has lagged behind those of ATG-dependent macroautophagy and ESCRT-dependent endosomal multivesicular body pathways. RESULTS: Here we show that as yeast cells gradually exhaust available nutrients and approach stationary phase, multiple vacuolar integral membrane proteins with unrelated functions are degraded in the vacuolar lumen. This degradation depends on the ESCRT machinery, but does not strictly require ubiquitination of cargos or trafficking of cargos out of the vacuole. It is also temporally and mechanistically distinct from NPC-dependent microlipophagy. The turnover is facilitated by Atg8, an exception among autophagy proteins, and an Atg8-interacting vacuolar membrane protein, Hfl1. Lack of Atg8 or Hfl1 led to the accumulation of enlarged lumenal membrane structures in the vacuole. We further show that a key function of Hfl1 is the membrane recruitment of Atg8. In the presence of Hfl1, lipidation of Atg8 is not required for efficient cargo turnover. The need for Hfl1 can be partially bypassed by blocking Atg8 delipidation. CONCLUSIONS: Our data reveal a vacuolar membrane protein degradation process with a unique dependence on vacuole-associated Atg8 downstream of ESCRTs, and we identify a specific role of Hfl1, a protein conserved from yeast to plants and animals, in membrane targeting of Atg8.


Assuntos
Saccharomyces cerevisiae , Vacúolos , Animais , Autofagia , Família da Proteína 8 Relacionada à Autofagia/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteínas de Membrana/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
17.
Sensors (Basel) ; 22(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35161463

RESUMO

To find an economical solution to infer the depth of the surrounding environment of unmanned agricultural vehicles (UAV), a lightweight depth estimation model called MonoDA based on a convolutional neural network is proposed. A series of sequential frames from monocular videos are used to train the model. The model is composed of two subnetworks-the depth estimation subnetwork and the pose estimation subnetwork. The former is a modified version of U-Net that reduces the number of bridges, while the latter takes EfficientNet-B0 as its backbone network to extract the features of sequential frames and predict the pose transformation relations between the frames. The self-supervised strategy is adopted during the training, which means the depth information labels of frames are not needed. Instead, the adjacent frames in the image sequence and the reprojection relation of the pose are used to train the model. Subnetworks' outputs (depth map and pose relation) are used to reconstruct the input frame, then a self-supervised loss between the reconstructed input and the original input is calculated. Finally, the loss is employed to update the parameters of the two subnetworks through the backward pass. Several experiments are conducted to evaluate the model's performance, and the results show that MonoDA has competitive accuracy over the KITTI raw dataset as well as our vineyard dataset. Besides, our method also possessed the advantage of non-sensitivity to color. On the computing platform of our UAV's environment perceptual system NVIDIA JETSON TX2, the model could run at 18.92 FPS. To sum up, our approach provides an economical solution for depth estimation by using monocular cameras, which achieves a good trade-off between accuracy and speed and can be used as a novel auxiliary depth detection paradigm for UAVs.


Assuntos
Redes Neurais de Computação , Aprendizado de Máquina Supervisionado , Fazendas
18.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36430180

RESUMO

Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammation. Extracellular histones play a role in inflammation and the conversion of latent pro-FSAP into active FSAP. FSAP has been shown to regulate endothelial permeability, but the mechanisms are not clear. Here, we have investigated the effects of FSAP on endothelial permeability in vitro. A mixture of histones from calf thymus stimulated permeability, and the wild-type (WT) serine protease domain (SPD) of FSAP blocked this effect. WT-SPD-FSAP did not influence permeability on its own, nor that stimulated by thrombin or vascular endothelial growth factor (VEGF)-A165. Histones induced a large-scale rearrangement of the junction proteins VE-cadherin and zona occludens-1 from a clear junctional distribution to a diffuse pattern. The presence of WT-SPD-FSAP inhibited these changes. Permeability changes by histones were blocked by both TLR-2 and TLR4 blocking antibodies. Histones upregulated the expression of TLR-2, but not TLR-4, in HUVEC cells, and WT-SPD-FSAP abolished the upregulation of TLR-2 expression. An inactive variant, Marburg I (MI)-SPD-FSAP, did not have any of these effects. The inhibition of histone-mediated permeability may be an important function of FSAP with relevance to sepsis, trauma, and stroke and the need to be investigated further in in vivo experiments.


Assuntos
Histonas , Fator A de Crescimento do Endotélio Vascular , Humanos , Inflamação , Permeabilidade , Serina Endopeptidases/metabolismo , Receptor 2 Toll-Like/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Surg Radiol Anat ; 44(1): 105-115, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34748048

RESUMO

PURPOSE: Multislice spiral CT (MSCT) was used to investigate the anatomical characteristics of sternal development, and to provide anatomical basis for sternal puncture in children. METHODS: We retrospectively analyzed the thoracic MSCT data of 600 children who received thoracic MSCT from January to June 2020 with their age ranging from 1 month to 19 years. The distribution of sternal ossification centers and adjacent tissues and organs was observed. Subcutaneous soft tissue thickness and the distance between the skin and the posterior margin of the sternum were measured in the central areas of sternal manubrium and mesosternum (segments I and II), and the correlation between the two was calculated using linear correlation. RESULTS: A total of 600 patients were enrolled, the mean age was 9.87 years and the standard deviation was 8.28 years. The sternal manubrium and ossification centers at the I and II segments of the mesosternum were visible in all cases (100%). There was no ossification in segment III of the mesosternum in 15 cases (2.5%), including 12 cases (80%) adjacent to the posterior pericardium and 7 cases (46.7%) of lung tissue. There were 274 cases (45.7%) of segment IV without ossification, including 204 cases (74.5%) of adjacent pericardium and 95 cases (32.8%) of lung tissue. The xiphoid process was not ossified in 258 cases (43%), including 190 cases (73.6%) adjacent to the pericardium and 97 cases (37.6%) adjacent to the lung tissue. Correspondingly, the thickness of subcutaneous soft tissue of the sternal manubrium and the central region of the I and II segments of the mesosternum had a low positive correlation with age (P < 0.001), the distance between the skin and the posterior margin of the sternum showed a moderate positive correlation with age (P < 0.001), and the distance between the skin and the posterior margin of the sternum showed a high positive correlation with the thickness of subcutaneous soft tissue (P < 0.001). CONCLUSIONS: Nonossification of the sternal ossification center usually occurs below segment III of the mesosternum and is usually adjacent to heart and lung tissue. Pediatric sternal puncture should be performed at the sternal manubrium and the mesosternum of segments I and II. However, attention should be paid to the space between multiple ossification centers. The thickness of subcutaneous soft tissue is a critical factor that determines the depth of the puncture.


Assuntos
Punções , Esterno , Criança , Humanos , Pericárdio , Estudos Retrospectivos , Esterno/diagnóstico por imagem , Tomografia Computadorizada Espiral
20.
J Org Chem ; 86(5): 4071-4080, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33620225

RESUMO

A straightforward and efficient methodology has been developed for the synthesis of 1,4,5-trisubstituted dicarbonyl 1,2,3-triazoles and 1,4-disubstituted sole-carbonyl 1,2,3-triazoles via a C-C bond cleavage process. The Regitz diazo transfer and C-C bond cleavage were the key steps of this transformation, which provided diverse carbonyl-substituted structural 1,2,3-triazoles. This reaction featured with excellent regioselectivity, wide functional group tolerance, and mild conditions.


Assuntos
Triazóis , Catálise , Estrutura Molecular
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