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1.
J Inorg Biochem ; 233: 111855, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35576884

RESUMO

Four neutral cyclometalated iridium(III) (IrIII) dithioformic acid complexes ([(ppy)2Ir(S^S)], Ir1-Ir4) were designed and synthesized. Toxicity assay revealed that these complexes showed favorable anticancer activity, especially for human non-small cell lung cancer cells (A549). Ir1 exhibited the best anticancer activity (11.0 ± 0.4 µM) was about twice that of cisplatin, meanwhile, which could availably restrain A549 cells migration. Complexes could target mitochondria, induce a decrease in mitochondrial membrane potential (MMP), result in an increase of intracellular reactive oxygen species (ROS) and disruption of the cell cycle, and ultimately generate apoptosis. Western blotting experiment indicated that complexes could inhibit the expression of B cell CLL/lymphoma-2 protein (Bcl-2), induce the expression of BCL2-associated X protein (Bax) and lead to a massive release of Cytochrome C (Cyt-c), which amplified apoptosis signals by activating downstream pathway to promote apoptosis. All these confirmed the existence of mitochondrial anticancer channels for these complexes. Above all, cyclometalated iridium(III) dithioformic acid complexes possess the prospect of becoming a multifunctional cancer therapeutic platform, including mitochondria-targeted imaging, anti-migration, and anticancer agents.

2.
Sci Rep ; 12(1): 7431, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523902

RESUMO

In order to solve the soil problem of poor structure and low fertility after the abandoned homestead reclamation of Hollow Village in Loess Area and to improve the quality of the reclaimed soil in Hollow Village, a five-year field experiment was conducted here. In this experiment, the following seven treatments were applied: no modified material (CK), maturing agent (TM), fly ash (TF), organic fertilizer (TO), maturing agent + fly ash (TMF), maturing agent + organic fertilizer (TMO) and fly ash + organic fertilizer (TFO), and the effects of different improved materials on soil properties and crop yield were studied. The results showed that: soil organic matter (SOM) and total nitrogen contents increased significantly after the application of different improved materials, which promoted the cementation and aggregation of water-stable microaggregates (< 0.25 mm), and the water-stable macroaggregates showed an increasing trend. In the 0-0.15 m soil layer, the proportion of water-stable macroaggregates under TM, TF, TO, TMF, TMO, and TFO treatment increased by 328.2%, 130.0%, 87.8%, 81.1%, 36.7%, and 12.2% compared with CK, respectively. Meanwhile, TF, TO, TMF, TMO, TFO treatments significantly increased the mean weight diameter (MWD) and geometric mean diameter (GMD) values, reduced soil bulk density, the stable aggregate index (ELT) and fractal dimension (D) values (P < 0.05), and the stability of soil structure and the capacity of soil moisture retention has been significantly improved. The SOM content had a significant positive correlation with MWD, GMD, and > 2 mm water-stable aggregates and a significant negative correlation with the ELT, D, and water-stable microaggregates. In particular, the organic-inorganic coupling treatment of TFO showed the highest SOM content, soil moisture content, water-stable macroaggregates and maize yield, which was the most appropriate amendment for improving the reclaimed soil structure and fertility of Hollow Village in Loess Area.


Assuntos
Fertilizantes , Solo , Agricultura/métodos , China , Cinza de Carvão , Nitrogênio , Solo/química , Água , Zea mays
3.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563299

RESUMO

Phospholipase Dα (PLDα), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Dδ (PLDδ) can mediate the salt response in higher plants. PePLDδ was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDδ-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDδ-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H2O2 levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDδ-overexpressed plants increased the transcription of genes encoding the plasma membrane Na+/H+ antiporter (AtSOS1) and H+-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na+ extrusion and reduce K+ loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K+/Na+ homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDδ. PePLDδ-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2), 36:5 (18:2-18:3) and 36:6 (18:3-18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2) and 36:5 (18:2-18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDδ-derived PA enhanced the salinity tolerance by regulating ROS and K+/Na+ homeostasis in Arabidopsis.

4.
J Healthc Eng ; 2022: 3035073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509706

RESUMO

Background: Gastric adenocarcinoma (GAD) is one of the most common tumors in the world and the prognosis is still very poor. Objective: We sought to identify reliable prognostic biomarkers for the progression of GAD and the sensitivity to drug therapy. Method: The RNA sequencing data of GAD was downloaded from the Cancer Genome Atlas (TCGA) database and used for analysis. Differentially expressed, immune-related lncRNA (DEIRlncRNA) was characterized by differential analysis and correlation analysis. Univariate Cox regression analysis was used to identify DEIRlncRNA associated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression analysis allowed us to determine a signature composed of eight IRlncRNAs. Based on this signature, we further performed gene set enrichment analysis (GSEA) and somatic mutation analysis to evaluate the ability of this signature to predict prognosis. Results: In total, 72 immune-related lncRNAs (DEIRlncRNAs) with prognostic value were identified. These lncRNAs were used to construct a model containing eight immune-related lncRNAs (8-IRlncRNAs). Based on this risk model, we divided GAD patients into high-risk and low-risk groups. The analysis showed that the prognosis of the two groups was different and that the high-risk group had worse overall survival (OS). Immune cell infiltration analysis showed that the proportion of memory B cells increased in the high-risk group while the proportion of macrophages M1, T cells, CD4 memory-activated cells, and T cell follicular helpers decreased. GSEA results showed that 8-IRlncRNA was significantly enriched in tumorigenesis pathways such as myc. The results of somatic mutation analysis showed that the CDH1 gene was significantly mutated in the high-risk group. Conclusion: A prognostic signature of 8-IRlncRNAs in GAD was established and this signature was able to predict the prognosis of GAD patients.


Assuntos
Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
5.
J Innate Immun ; : 1-15, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537415

RESUMO

Humans with dysfunctional Bruton's tyrosine kinase (Btk) are highly susceptible to bacterial infections. Compelling evidence indicates that Btk is essential for B cell-mediated immunity, whereas its role in myeloid cell-mediated immunity against infections is controversial. In this study, we determined the contribution of Btk in B cells and neutrophils to host defense against the extracellular bacterial pathogen Klebsiella pneumoniae, a common cause of pulmonary infections and sepsis. Btk-/- mice were highly susceptible to Klebsiella infection, which was not reversed by Btk re-expression in B cells and restoration of natural antibody levels. Neutrophil-specific Btk deficiency impaired host defense against Klebsiella to a similar extent as complete Btk deficiency. Neutrophil-specific Btk deficiency abolished extracellular reactive oxygen species production in response to Klebsiella. These data indicate that expression of Btk in neutrophils is crucial, while in B cells, it is dispensable for in vivo host defense against K. pneumoniae.

6.
Front Plant Sci ; 13: 881456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574123

RESUMO

In plants, the leaf is an essential photosynthetic organ, and is the primary harvest in forage crops such as alfalfa (Medicago sativa). Premature leaf senescence caused by environmental stress can result in significant yield loss and quality reduction. Therefore, the stay-green trait is important for improving the economic value of forage crops. Alkaline stress can severely damage leaf cells and, consequently, cause leaf senescence. To understand the molecular regulatory mechanisms and identify vital senescence-associated genes under alkaline stress, we used high-throughput sequencing to study transcriptional changes in Medicago truncatula, a model plant for forage crops. We identified 2,165 differentially expressed genes, 985 of which were identical to those in the dark-induced leaf senescence group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the 985 genes were mainly enriched in nutrient cycling processes such as cellular amino acid metabolic processes and organic substance catabolic processes, indicating nutrient redistribution. The other 1,180 differentially expressed genes were significantly enriched in the oxidoreductase complex, aerobic respiration, and ion transport. Our analysis showed the two gene sets guiding the coupled physiological and biochemical alterations play different roles under alkaline stress with a coordinated and integrated way. Many transcription factor families were identified from these differentially expressed genes, including MYB, WRKY, bHLH, and NAC which have particular preference involved in stress resistance and regulation of senescence. Our results contribute to the exploration of the molecular regulatory mechanisms of leaf senescence in M. truncatula under alkaline stress and provide new candidate genes for future breeding to improve the biomass and quality of forage crops.

7.
Nat Genet ; 54(4): 481-491, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35410381

RESUMO

Mammalian chromosomes are organized into megabase-sized compartments that are further subdivided into topologically associating domains (TADs). While the formation of TADs is dependent on cohesin, the mechanism behind compartmentalization remains enigmatic. Here, we show that the bromodomain and extraterminal (BET) family scaffold protein BRD2 promotes spatial mixing and compartmentalization of active chromatin after cohesin loss. This activity is independent of transcription but requires BRD2 to recognize acetylated targets through its double bromodomain and interact with binding partners with its low-complexity domain. Notably, genome compartmentalization mediated by BRD2 is antagonized on the one hand by cohesin and on the other hand by the BET homolog protein BRD4, both of which inhibit BRD2 binding to chromatin. Polymer simulation of our data supports a BRD2-cohesin interplay model of nuclear topology, in which genome compartmentalization results from a competition between loop extrusion and chromatin-state-specific affinity interactions.


Assuntos
Proteínas Nucleares , Fatores de Transcrição , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/genética , Cromossomos/genética , Cromossomos/metabolismo , Mamíferos/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Domínios Proteicos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
Crit Rev Food Sci Nutr ; : 1-31, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442834

RESUMO

Cereals provide humans with essential nutrients, and its quality assessment has attracted widespread attention. Infrared (IR) spectroscopy (IRS) and hyperspectral imaging (HSI), as powerful nondestructive testing technologies, are widely used in the quality monitoring of food and agricultural products. Artificial intelligence (AI) plays a crucial role in data mining, especially in recent years, a new generation of AI represented by deep learning (DL) has made breakthroughs in analyzing spectral data of food and agricultural products. The combination of IRS/HSI and AI further promotes the development of quality evaluation of cereals. This paper comprehensively reviews the advances of IRS and HSI combined with AI in the detection of cereals quality. The aim is to present a complete review topic as it touches the background knowledge, instrumentation, spectral data processing (including preprocessing, feature extraction and modeling), spectral interpretation, etc. To suit this goal, principles of IRS and HSI, as well as basic concepts related to AI are first introduced, followed by a critical evaluation of representative reports integrating IRS and HSI with AI. Finally, the advantages, challenges and future trends of IRS and HSI combined with AI are further discussed, so as to provide constructive suggestions and guidance for researchers.

9.
Front Bioeng Biotechnol ; 10: 882308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480969

RESUMO

The majority of current nanocarriers in cancer treatment fail to deliver encapsulated cargos to their final targets at therapeutic levels, which decreases the ultimate efficacy. In this work, a novel core-shell nanocarrier with a biodegradable property was synthesized for efficient drug release and subcellular organelle delivery. Initially, silver nanoparticles (AgNPs) were grafted with terminal double bonds originating from N, N'-bisacrylamide cystamine (BAC). Then, the outer coatings consisting of chitosan (CTS) and polyvinyl alcohol (PVA) were deposited on the surface of modified AgNPs using an emulsion method. To improve the stability, disulfide-containing BAC was simultaneously reintroduced to cross-link CTS. The as-prepared nanoparticles (CAB) possessed the desired colloidal stability and exhibited a high drug loading efficiency of cationic anticancer agent doxorubicin (DOX). Furthermore, CAB was tailored to transform their size into ultrasmall nanovehicles responding to weak acidity, high glutathione (GSH) levels, and overexpressed enzymes. The process of transformation was accompanied by sufficient DOX release from CAB. Due to the triple sensitivity, CAB enabled DOX to accumulate in the nucleus, leading to a great effect against malignant cells. In vivo assays demonstrated CAB loading DOX held excellent biosafety and superior antitumor capacity. Incorporating all the benefits, this proposed nanoplatform may provide valuable strategies for efficient drug delivery.

10.
Infect Drug Resist ; 15: 1753-1765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431560

RESUMO

Introduction: This study was aimed to examine the clinical and epidemiological characteristics of sporotrichosis in China and specifically Jilin Province, which is one of the areas with the highest incidence worldwide, and to provide data support for the global prevalence of sporotrichosis. Methods: A total of 4969 cases of sporotrichosis diagnosed at the Second Hospital of Jilin University from January 1, 1990 to December 31, 2019 were collected. Results: In Jilin Province, the male-to-female ratio was 1:2, the average age at onset was 48 ± 1 years, and the average disease duration was 4.8 ± 2.7 months. The most susceptible individuals were farmers. Cases occurred more commonly in the winter and spring (71.5%) than in the summer and autumn (28.5%). The fixed type infection was more prevalent. Among the cases, 64.8% showed typical mycological changes, and 77.6% showed atypical pathological changes. Regarding the epidemiological characteristics of sporotrichosis in China, 6565 cases were retrieved from the literature from January 1, 2010 to December 31, 2019. Among them, the most affected area was Jilin Province, followed by Heilongjiang Province, and Liaoning Province. The male-to-female ratio was 1:1.46. The fixed type infection was the most common. A total of 241 strains were identified by molecular biotechnology; among these, 217 were identified as Sporothrix globosa and 24 were identified as S. schenckii sensu stricto. Discussion: The results add clarity to the clinical epidemiology of sporotrichosis in China and specifically Jilin Province. We believe these data will help improve the epidemiology knowledge of sporotrichosis worldwide.

11.
Biosci Trends ; 2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35431288

RESUMO

Hepatocellular carcinoma (HCC) has been the fifth most common malignancy worldwide and is the second most common cause of tumor-related mortality globally. In China, a high proportion of patients with HCC present with an advanced stage of the disease, so HCC is a major challenge to the healthcare system and a substantial socioeconomic burden. The last decade has witnessed an expansion of the treatment landscape for HCC. Various approaches have been explored as potential conversion therapies for advanced HCC. Despite controversies, mounting data have indicated that successful conversion therapy followed by subsequent surgery is achievable in a population of patients with advanced HCC. This conversion therapy is a safe and promising treatment strategy to prolong long-term outcomes. Based on preliminary research, this review has assembled and summarized current clinical experience with and evidence of the efficacy of conversion therapies followed by subsequent surgery for advanced HCC.

12.
Insects ; 13(4)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35447833

RESUMO

With the wide-scale adoption of transgenic Bacillus thuringiensis (Bt) cotton, Apolygus lucorum (Meyer-Dür) has become the most serious pest and has caused extensive yield loss in cotton production. However, little is known about the defense responses of cotton at the seedling stage to A. lucorum feeding. In this study, to elucidate the cotton defense mechanism, cotton leaves were damaged by A. lucorum for 0, 4, 12 and 24 h. The transcriptomic results showed that A. lucorum feeding elicits a rapid and strong defense response in gene expression during the whole infestation process in cotton plants. Further analysis revealed that at each assessment time, more differentially expressed genes were up-regulated than down-regulated. The integrated analysis of transcriptomic and metabolic data showed that most of the genes involved in jasmonic acid (JA) biosynthesis were initially up-regulated, and this trend continued during an infestation. Meanwhile, the content levels of JA and its intermediate products were also significantly increased throughout the whole infestation process. The similar trend was displayed in condensed tannins biosynthesis. This research proved that, after plants are damaged by A. lucorum, the JA pathway mediates the defense mechanisms in cotton plants by promoting the accumulation of condensed tannins as a defense mechanism against A. lucorum. These results will help us to discover unknown defensive genes and improve the integrated pest management of A. lucorum.

13.
Int J Ophthalmol ; 15(4): 554-559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450169

RESUMO

AIM: To investigate the effect of leptin on the angiogenesis of RF/6A cells (monkey retinal choroidal endothelial cells) in vitro and test the cellular signaling in the mechanism. METHODS: RF/6A cells were cultured in vitro and randomly divided into four groups: normal control, with leptin at 50, 100, 200 ng/mL for cell counting kit-8 (CCK8). RF/6A cell proliferation and migration were examined by Transwell assays, while RF/6A cell tube formation by Matrigel assay. JAK2, p-JAK2, STAT3, and p-STAT3 protein expression was measured by Western blotting. Cells were then divided into the following treatment groups: control, 100 ng/mL leptin and AG-490 (100 ng/mL leptin+10 µmol/L AG-490) for examinations of RF/6A cellular behaviour again. Analysis of differences was carried out using one-way ANOVA and least significant difference (LSD). RESULTS: RF/6A cell proliferation, migration and cell tube formation were promoted significantly by leptin in a dose-dependent manner (P<0.05). Western blotting showed that leptin up-regulated p-JAK2 and p-STAT3 expression levels. Treatment with the JAK/STAT pathway inhibitor, AG-490, decreased leptin-induced p-JAK2 and p-STAT3 expression, and inhibited cell proliferation, migration and cell tube formation induced by leptin (P<0.05). CONCLUSION: Leptin can promote RF/6A cell angiogenesis in vitro via activation of the JAK2/STAT3 signaling pathway.

15.
Molecules ; 27(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35408465

RESUMO

Lactic acid bacteria (LAB) produce antimicrobial substances that could potentially inhibit the growth of pathogenic and food spoilage microorganisms. Lacticaseibacillus rhamnosus XN2, isolated from yak yoghurt, demonstrated antibacterial activity against Bacillus subtilis, B. cereus, Micrococcus luteus, Brochothrix thermosphacta, Clostridium butyricum, S. aureus, Listeria innocua CICC 10416, L. monocytogenes, and Escherichia coli. The antibacterial activity was estimated to be 3200 AU/mL after 30 h cultivation. Time-kill kinetics curve showed that the semi-purified cell-free supernatants (CFS) of strain XN2 possessed bactericidal activity. Flow cytometry analysis indicated disruption of the sensitive bacteria membrane by semi-purified CFS, which ultimately caused cell death. Interestingly, sub-lethal concentrations of semi-purified CFS were observed to reduce the production of α-haemolysin and biofilm formation. We further investigated the changes in the transcriptional level of luxS gene, which encodes signal molecule synthase (Al-2) induced by semi-purified CFS from strain XN2. In conclusion, L. rhamnosus XN2 and its bacteriocin showed antagonistic activity at both cellular and quorum sensing (QS) levels. Finally, bacteriocin was further purified by reversed-phase high-performance liquid chromatography (RP-HPLC), named bacteriocin XN2. The amino acid sequence was Met-Lue-Lys-Lys-Phe-Ser-Thr-Ala-Tyr-Val.


Assuntos
Bacteriocinas , Síndrome de Fadiga Crônica , Lactobacillus rhamnosus , Animais , Antibacterianos , Bovinos , Staphylococcus aureus , Iogurte
16.
Oncogene ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440714

RESUMO

The H3K4 demethylase KDM5B is overexpressed in multiple cancer types, and elevated expression levels of KDM5B is associated with decreased survival. However, the underlying mechanistic contribution of dysregulated expression of KDM5B and H3K4 demethylation in cancer is poorly understood. Our results show that loss of KDM5B in multiple types of cancer cells leads to increased proliferation and elevated expression of cancer stem cell markers. In addition, we observed enhanced tumor formation following KDM5B depletion in a subset of representative cancer cell lines. Our findings also support a role for KDM5B in regulating epigenetic plasticity, where loss of KDM5B in cancer cells with elevated KDM5B expression leads to alterations in activity of chromatin states, which facilitate activation or repression of alternative transcriptional programs. In addition, we define KDM5B-centric epigenetic and transcriptional patterns that support cancer cell plasticity, where KDM5B depleted cancer cells exhibit altered epigenetic and transcriptional profiles resembling a more primitive cellular state. This study also provides a resource for evaluating associations between alterations in epigenetic patterning upon depletion of KDM5B and gene expression in a diverse set of cancer cells.

17.
Sci Total Environ ; 831: 154931, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364181

RESUMO

The distal lung (G14-G23), which are composed of alveoli and bronchi, are responsible for almost all gas exchange and micro- and nanoparticle deposition in the lungs. In the existing research using computational fluid dynamics, the geometric modeling accuracy of the bronchial bifurcation structure is given priority, and then the alveoli are attached to bronchi as discrete spherical crowns. This method ignores the correlation between alveoli. In fact, the alveoli have a tessellated distribution, and adjacent alveoli are connected by several alveolar pores. Due to the huge number of alveoli, this seemingly small difference will be greatly amplified, which may lead to a large deviation in the prediction of the overall flow. Accordingly, the objective of this study is to construct a two-dimensional distal lung model including the bronchi, acini, and alveolar pores by using the methods of regular hexagonal tessellational subdivision, fusion, and coordinate transformation. A moving boundary is introduced to simulate the process of airflow and particle deposition in the distal lung, and the effects of bronchial deformation, respiratory frequency, and alveolar pores are obtained. The results show that there are significant differences in intrapulmonary flow patterns with and without alveolar pores. Alveolar pores can establish bypass ventilation downstream of a blockage, thus providing a pathway for particles to enter the airways downstream of the blockage. Changing the respiratory frequency and the amplitude of bronchial deformation will change the relative velocity between particles and moving wall, which, in turn, will change the particle deposition efficiency in the distal lung. To summarize this study, a geometric modeling method for the distal lung with alveolar pores is established, and the important roles of detailed characteristics of the distal lung are revealed. The findings of this study provide a reasonable hydrodynamic mechanism for the prevention of related respiratory diseases.

18.
Cancer Gene Ther ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422087

RESUMO

Mitochondrial serine hydroxymethyltransferase (SHMT2) catalyzes the conversion of serine to glycine and concomitantly produces one-carbon units to support cell growth and is upregulated in various cancer cells. SHMT2 knockdown triggers cell apoptosis; however, the detailed mechanism of apoptosis induced by SHMT2 inactivation remains unknown. Here, we demonstrate that SHMT2 supports the proliferation of bladder cancer (BC) cells by maintaining redox homeostasis. SHMT2 knockout decreased the pools of purine and one-carbon units and delayed cell cycle progression in a manner that was rescued by formate, demonstrating that SHMT2-mediated one-carbon units are essential for BC cell proliferation. SHMT2 deficiency promoted the accumulation of intracellular reactive oxygen species (ROS) by decreasing the NADH/NAD+, NADPH/NADP+, and GSH/GSSG ratios, leading to a loss in mitochondrial membrane potential, release of cytochrome c, translocation of Bcl-2 family protein and activation of caspase-3. Notably, blocking ROS production with the one-carbon donor formate and the ROS scavenger N-acetyl-cysteine (NAC) effectively rescued SHMT2 deficiency-induced cell apoptosis via the intrinsic signaling pathway. Treatment with the SHMT inhibitor SHIN1 resulted in a significant inhibitory effect on cell proliferation and induced cell apoptosis. Formate and NAC rescued SHIN1-induced cell apoptosis. Our findings reveal an important mechanism by which the loss of SHMT2 triggers ROS-dependent, mitochondrial-mediated apoptosis, which gives insight into the link between serine metabolism and cell apoptosis and provides a promising target for BC treatment and drug discovery.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35420991

RESUMO

Despite the substantial progress made by deep networks in the field of medical image segmentation, they generally require sufficient pixel-level annotated data for training. The scale of training data remains to be the main bottleneck to obtain a better deep segmentation model. Semi-supervised learning is an effective approach that alleviates the dependence on labeled data. However, most existing semi-supervised image segmentation methods usually do not generate high-quality pseudo labels to expand training dataset. In this paper, we propose a deep semi-supervised approach for liver CT image segmentation by expanding pseudo-labeling algorithm under the very low annotated-data paradigm. Specifically, the output features of labeled images from the pretrained network combine with corresponding pixel-level annotations to produce class representations according to the mean operation. Then pseudo labels of unlabeled images are generated by calculating the distances between unlabeled feature vectors and each class representation. To further improve the quality of pseudo labels, we adopt a series of operations to optimize pseudo labels. A more accurate segmentation network is obtained by expanding the training dataset and adjusting the contributions between supervised and unsupervised loss. Besides, the novel random patch based on prior locations is introduced for unlabeled images in the training procedure. Extensive experiments show our method has achieved more competitive results compared with other semi-supervised methods when fewer labeled slices of LiTS dataset are available.

20.
J Healthc Eng ; 2022: 6388068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480149

RESUMO

The student's attitude towards the doctor-nurse integrated teaching model and Maslow's hierarchy of needs theory is an important topic in clinical teaching. In this study, choosing 134 intern doctors and practice nurses who intern from January to December 2020. 67 students are selected as the control group, and the traditional interns teaching mode is adopted. 67 students are selected as the experimental group and Maslow's hierarchy of needs theory to apply in the doctor-nurse integrated teaching mode. The results show that the doctor-nurse integrated teaching model are accepted by most students, and the application of Maslow's hierarchy of needs theory in the clinical interns has advantages over the traditional model.


Assuntos
Médicos , Humanos , Estudantes
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