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1.
Infect Drug Resist ; 14: 4795-4807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815677

RESUMO

Purpose: To investigate the dysregulated pathways and identify reliable diagnostic biomarkers for tuberculosis using integrated analysis of metabolomics and transcriptomics. Methods: Three groups of samples, untargeted metabolomics analysis of healthy controls (HC), latent tuberculosis infection patients (LTBI), and active tuberculosis patients (TB), were analyzed using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and ultra-high performance liquid chromatography-quantitative mass spectrometry (UHPLC-QE-MS). Both univariate and multivariate and statistical analyses were used to select differential metabolites (DMs) among group comparison, and LASSO regression analysis was employed to discover potential diagnostic biomarkers. Metabolite set enrichment analysis was performed to identify the altered metabolic pathways specifically in patients with TB. Meanwhile, a transcriptomic dataset GSEG4992 was downloaded from the GEO database to explore the differentially expressed genes (DEGs) between TB and HC identified in significantly enriched pathways. Finally, an integrative analysis of DMs and DEGs was performed to investigate the possible molecular mechanisms of TB. Results: Thirty-three specific metabolites were significantly different between TB and HC, of which 7 (5-hydroxyindoleacetic acid, isoleucyl-isoleucine, heptadecanoic acid, indole acetaldehyde, 5-ethyl-2,4-dimethyloxazole, and 2-hydroxycaproic acid, unknown 71) were chosen as combinational potential biomarkers for TB. The area under the curve (AUC) value of these biomarkers was 0.97 (95% CI: 0.92-1.00). Metabolites set enrichment analysis (MSEA) displayed that there were 3 significantly enriched pathways among all. The genes in 3 significantly enriched pathways were further analyzed, of which 9(ALDH3B1, BCAT1, BCAT2, GLYAT, GOT1, IL4I1, MIF, SDS, SDSL) were expressed differentially. The area under the curve (AUC) values of these DEGs enriched in pathways mostly were greater than 0.8. As a result, a connected network of metabolites and genes in the pathways were established, which provides insights into the credibility of selected metabolites. Conclusion: The newly identified metabolic biomarkers display a high potential to be developed into a promising tool for TB screening, diagnosis, and therapeutic effect monitoring.

3.
Drug Deliv ; 28(1): 2329-2347, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34730054

RESUMO

In recent years, the incidence of various types of tumors has gradually increased, and it has also been found that there is a certain correlation between abnormal glucose and lipid metabolism and tumors. Glycolipid metabolism can promote tumor progression through multiple pathways, and the expression of related genes also directly or indirectly affects tumor metabolism, metastasis, invasion, and apoptosis. There has been much research on targeted drug delivery systems designed for abnormal glucose and lipid metabolism due to their accuracy and efficiency when used for tumor therapy. In addition, gene mutations have become an important factor in tumorigenesis. For this reason, gene therapy consisting of drugs designed for certain specifically expressed genes have been transfected into target cells to express or silence the corresponding proteins. Targeted gene drug vectors that achieve their corresponding therapeutic purposes are also rapidly developing. The genes related to glucose and lipid metabolism are considered as the target, and a corresponding gene drug carrier is constructed to influence and interfere with the expression of related genes, so as to block the tumorigenesis process and inhibit tumor growth. Designing drugs that target genes related to glucose and lipid metabolism within tumors is considered to be a promising strategy for the treatment of tumor diseases. This article summarizes the chemical drugs/gene drug delivery systems and the corresponding methods used in recent years for the treatment of abnormal glucose and lipid metabolism of tumors, and provides a theoretical basis for the development of glucolipid metabolism related therapeutic methods.

4.
Adv Sci (Weinh) ; : e2103608, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34821070

RESUMO

Formation of blood clots, particularly the fibrin network and fibrin network-mediated early inflammatory responses, plays a critical role in determining the eventual tissue repair or regeneration following an injury. Owing to the potential role of fibrin network in mediating clot-immune responses, it is of great importance to determine whether clot-immune responses can be regulated via modulating the parameters of fibrin network. Since the diameter of D-terminal of a fibrinogen molecule is 9 nm, four different pore sizes (2, 8, 14, and 20 nm) are rationally selected to design mesoporous silica to control the fibrinogen adsorption and modulate the subsequent fibrin formation process. The fiber becomes thinner and the contact area with macrophages decreases when the pore diameters of mesoporous silica are greater than 9 nm. Importantly, these thinner fibers grown in pores with diameters larger than 9 nm inhibit the M1-polorazation of macrophages and reduce the productions of pro-inflammatory cytokines and chemokines by macrophages. These thinner fibers reduce inflammation of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton assembly-inflammatory responses. Thus, the successful regulation of the clot-immune responses via tuning of the mesoporous pore sizes indicates the feasibility of developing advanced clot-immune regulatory materials.

5.
Nat Commun ; 12(1): 6858, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824214

RESUMO

Muntjac deer have experienced drastic karyotype changes during their speciation, making it an ideal model for studying mechanisms and functional consequences of mammalian chromosome evolution. Here we generated chromosome-level genomes for Hydropotes inermis (2n = 70), Muntiacus reevesi (2n = 46), female and male M. crinifrons (2n = 8/9) and a contig-level genome for M. gongshanensis (2n = 8/9). These high-quality genomes combined with Hi-C data allowed us to reveal the evolution of 3D chromatin architectures during mammalian chromosome evolution. We find that the chromosome fusion events of muntjac species did not alter the A/B compartment structure and topologically associated domains near the fusion sites, but new chromatin interactions were gradually established across the fusion sites. The recently borne neo-Y chromosome of M. crinifrons, which underwent male-specific inversions, has dramatically restructured chromatin compartments, recapitulating the early evolution of canonical mammalian Y chromosomes. We also reveal that a complex structure containing unique centromeric satellite, truncated telomeric and palindrome repeats might have mediated muntjacs' recurrent chromosome fusions. These results provide insights into the recurrent chromosome tandem fusion in muntjacs, early evolution of mammalian sex chromosomes, and reveal how chromosome rearrangements can reshape the 3D chromatin regulatory conformations during species evolution.

6.
J Mol Histol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751841

RESUMO

Gastric cancer (GC) is one of the most common malignancies, ranking the third highest mortality rate worldwide. Due to the insidious symptoms and difficulty in early detection, patients with GS were mostly in the middle and late stages when they were diagnosed. Although ontogenetic or tumor-suppressive effects of miRNA-200a-3p have been demonstrated, the exact mechanism underlying GC is not clear. Therefore, the expression, effect, and mechanism of miRNA-200a-3p in GC progression were systematically investigated in this study. qRT-PCR, Western blotting, and immunohistochemical staining were applied to investigate the miRNA-200a-3p and deleted in liver cancer 1 (DLC-1) expression. Cell viability, proliferation, apoptosis, migration, and invasion capabilities of GC cells were assessed using cell counting kit-8 (CCK-8) colorimetry, EdU integration, flow cytometry, wound healing, and the transwell assay. The relationship between miRNA-200a-3p and tumor growth was investigated by tumor xenograft assay in vivo. A dual-luciferase reporter assay was estimated to verify the connection between miR-200-3p and DLC-1. The results showed that miRNA-200a-3p expression was significantly increased in both GC tissues and cells. Furthermore, via DLC-1, miRNA-200a-3p promotes tumor growth and development. miRNA-200a-3p, by targeting DLC-1, can function as an oncogene in GC cells. Collectively, our findings indicated that the miRNA-200a-3p/DLC axis might provide a theological basis for potential improvements in GC treatment strategies.

8.
Int J Mol Sci ; 22(22)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34830341

RESUMO

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

9.
Membranes (Basel) ; 11(11)2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34832103

RESUMO

The nutrient removal and biomass production of the internal circulating fluidized bed microalgae membrane bioreactor (ICFB-MMBR) was studied under different cultivation modes, influent TOC, influent pH, and influent N/P. Platymonas helgolandica tsingtaoensis was used as the biological source. The growth of P. helgolandica tsingtaoensis and the removal efficiency of pollutants in the mixotrophy culture mode were improved compared with other culture modes. With the increased influent TOC, the average growth rate of P. helgolandica tsingtaoensis increased, and ammonia nitrogen and total phosphorus removal rate were improved. The P. helgolandica tsingtaoensis growth rate and nutrient removal efficiencies at the influent pH of 8 were the best among the different influent pH values. As the influent N/P ratio increased from 5 to 20, the P. helgolandica tsingtaoensis growth rate and pollutant removal rate increased gradually. When the influent N/P ratio was higher than 20, the P. helgolandica tsingtaoensis growth rate and pollutant removal rate tended to be stable and did not significantly change with the increase of influent N/P ratio. At the proper influent conditions, the high P. helgolandica tsingtaoensis biomass and nutrient removal efficiency could be obtained in the microalgae membrane bioreactor, which could provide a theoretical basis for the application of the system for wastewater treatment.

10.
World J Gastrointest Oncol ; 13(9): 1099-1108, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34616515

RESUMO

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.

11.
Front Neurol ; 12: 752164, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712200

RESUMO

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs. Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients. Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905-3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017-3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190-6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037-3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts. Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort.

12.
Front Psychiatry ; 12: 748064, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658979

RESUMO

Previous cross-sectional studies have documented that sleep reactivity was associated with depressive symptoms, but the potential mechanisms underlying this relationship were understudied. Therefore, the present study with a longitudinal prospective design was to reveal the mediating roles of sleep disturbance and emotion regulation difficulties (ERD) between sleep reactivity and depressive symptoms. This study included 725 student nurses who were followed up periodically for 9 months, with an interval of three months. All participants completed questionnaires regarding sleep reactivity, sleep disturbance, ERD, and depressive symptoms. Adjusted analyses suggested that the direct effect of sleep reactivity on depressive symptoms was non-significant. The bootstrap procedure revealed two significant indirect effects: from sleep reactivity to depressive symptoms with sleep disturbance as a mediator and from sleep reactivity to depressive symptoms with sleep disturbance and ERD as sequential mediators. Therefore, sleep reactivity might be considered as an indicator of shiftwork adaptability in the evaluation of recruitment. Psychological interventions aimed at developing healthy sleep habits and emotion regulation skills may be helpful in decreasing the risk of depression.

13.
Membranes (Basel) ; 11(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34677495

RESUMO

The mariculture wastewater treatment performance for the combined system of anoxic filter and membrane bioreactor (AF-MBR) was investigated under different hydraulic retention times (HRTs), influent alkalinity, and influent ammonia nitrogen load. The results showed that the removal efficiencies of TOC and total nitrogen were slightly better at the HRT of 8 h than at other HRTs, and the phosphate removal efficiency decreased with the increase of HRT. With the increase of influent alkalinity, the removal of TOC and phosphate did not change significantly. With the increase of influent alkalinity from 300 mg/L to 500 mg/L, the total nitrogen removal efficiency of AF-MBR was improved, but the change of the removal efficiency was not obvious when the alkalinity increased from 500 mg/L to 600 mg/L. When the influent concentration of ammonia nitrogen varied from 20 mg/L to 50 mg/L, the removal efficiencies of TOC, phosphate, and total nitrogen by AF-MBR were stable. An interesting finding was that in all the different operation conditions examined, the treatment efficiency of AF-MBR was always better than that of the control MBR. The concentrations of NO3--N in AF-MBR were relatively low, whereas NO3--N accumulated in the control MBR. The reason was that the microorganisms attached to the carrier and remained fixed in the aerobic and anoxic spaces, so that there was a gradual enrichment of bacteria characterized by slow growth in a high-salt environment. In addition, the microorganisms could gather and grow on the carrier forming a biofilm with higher activity, a richer and more stable population, and enhanced ability to resist a load impact.

14.
Genes (Basel) ; 12(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34681034

RESUMO

Donkeys are an important domesticated animal, providing labor, meat, milk, and medicinal materials for humans. However, the donkey population is continuously declining and even at risk of extinction. The application of modern animal production technology, such as oocyte in vitro maturation, is a promising method to improve the donkey population. In this study, we explore the gene expression patterns of donkey germinal vesicle (GV) and in vitro matured metaphase II (MII) oocytes using single cell RNA-seq of the candidate genes along with the regulatory mechanisms that affect donkey oocyte maturation. We identified a total of 24,164 oocyte genes of which 9073 were significant differentially expressed in the GV and MII oocytes. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these genes were associated with the meiotic cell cycle, mitochondrion activity, and N-glycan biosynthesis, which might be the key genes and regulatory mechanisms affecting the maturation of donkey oocytes. Our study provides considerable understanding regarding the maturation of donkey oocytes and serves as a theoretical basis for improving the development of donkey oocytes, which could ultimately benefit the expansion of the donkey population and conservation of biodiversity and genetic resources.

15.
J Healthc Eng ; 2021: 9236369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630999

RESUMO

In order to enable obese adolescents to increase muscle content, base metabolism, etc., aerobic training is used reduce body fat and then improve body components, health physique indicators, and physical fitness. This paper adopts the current situation for research and model construction through the K-center algorithm. The results show that 10 min swimming movement increased the adolescent patients' level of brain metabolism, and with no less than 15 min, the CI value rose to 41, the increase in brain metabolism in adolescents, and the rate of fat combustion effectively increased. It is guaranteed that physical health prevents the occurrence of obese syndrome diseases. Sports training can not only increase the skinny weight of the teen obese population but also reduce body fat content, which has a significant assistance to body type, is a high-cost performance, and has comprehensive training means.

16.
PLoS Negl Trop Dis ; 15(10): e0009750, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34610021

RESUMO

Fasciola gigantica and Fasciola hepatica are causative pathogens of fascioliasis, with the widest latitudinal, longitudinal, and altitudinal distribution; however, among parasites, they have the largest sequenced genomes, hindering genomic research. In the present study, we used various sequencing and assembly technologies to generate a new high-quality Fasciola gigantica reference genome. We improved the integration of gene structure prediction, and identified two independent transposable element expansion events contributing to (1) the speciation between Fasciola and Fasciolopsis during the Cretaceous-Paleogene boundary mass extinction, and (2) the habitat switch to the liver during the Paleocene-Eocene Thermal Maximum, accompanied by gene length increment. Long interspersed element (LINE) duplication contributed to the second transposon-mediated alteration, showing an obvious trend of insertion into gene regions, regardless of strong purifying effect. Gene ontology analysis of genes with long LINE insertions identified membrane-associated and vesicle secretion process proteins, further implicating the functional alteration of the gene network. We identified 852 predicted excretory/secretory proteins and 3300 protein-protein interactions between Fasciola gigantica and its host. Among them, copper/zinc superoxide dismutase genes, with specific gene copy number variations, might play a central role in the phase I detoxification process. Analysis of 559 single-copy orthologs suggested that Fasciola gigantica and Fasciola hepatica diverged at 11.8 Ma near the Middle and Late Miocene Epoch boundary. We identified 98 rapidly evolving gene families, including actin and aquaporin, which might explain the large body size and the parasitic adaptive character resulting in these liver flukes becoming epidemic in tropical and subtropical regions.

17.
PLoS Pathog ; 17(10): e1010001, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34648596

RESUMO

Sexual reproduction is an essential stage of the oomycete life cycle. However, the functions of critical regulators in this biological process remain unclear due to a lack of genome editing technologies and functional genomic studies in oomycetes. The notorious oomycete pathogen Pythium ultimum is responsible for a variety of diseases in a broad range of plant species. In this study, we revealed the mechanism through which PuM90, a stage-specific Puf family RNA-binding protein, regulates oospore formation in P. ultimum. We developed the first CRISPR/Cas9 system-mediated gene knockout and in situ complementation methods for Pythium. PuM90-knockout mutants were significantly defective in oospore formation, with empty oogonia or oospores larger in size with thinner oospore walls compared with the wild type. A tripartite recognition motif (TRM) in the Puf domain of PuM90 could specifically bind to a UGUACAUA motif in the mRNA 3' untranslated region (UTR) of PuFLP, which encodes a flavodoxin-like protein, and thereby repress PuFLP mRNA level to facilitate oospore formation. Phenotypes similar to PuM90-knockout mutants were observed with overexpression of PuFLP, mutation of key amino acids in the TRM of PuM90, or mutation of the 3'-UTR binding site in PuFLP. The results demonstrated that a specific interaction of the RNA-binding protein PuM90 with the 3'-UTR of PuFLP mRNA at the post-transcriptional regulation level is critical for the sexual reproduction of P. ultimum.


Assuntos
Pythium/fisiologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regiões 3' não Traduzidas , Doenças das Plantas/microbiologia , Reprodução
18.
Nat Biomed Eng ; 5(10): 1217-1227, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34654900

RESUMO

Monitoring surgical wounds post-operatively is necessary to prevent infection, dehiscence and other complications. However, the monitoring of deep surgical sites is typically limited to indirect observations or to costly radiological investigations that often fail to detect complications before they become severe. Bioelectronic sensors could provide accurate and continuous monitoring from within the body, but the form factors of existing devices are not amenable to integration with sensitive wound tissues and to wireless data transmission. Here we show that multifilament surgical sutures functionalized with a conductive polymer and incorporating pledgets with capacitive sensors operated via radiofrequency identification can be used to monitor physicochemical states of deep surgical sites. We show in live pigs that the sutures can monitor wound integrity, gastric leakage and tissue micromotions, and in rodents that the healing outcomes are equivalent to those of medical-grade sutures. Battery-free wirelessly operated bioelectronic sutures may facilitate post-surgical monitoring in a wide range of interventions.

19.
Mol Neurobiol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34708331

RESUMO

Hearing loss is the most common human sensory deficit. Hearing relies on stereocilia, inserted into the cuticular plate of hair cells (HCs), where they play an important role in the perception of sound and its transmission. Although numerous genes have been associated with hearing loss, the function of many hair cell genes has yet to be elucidated. Herein, we focused on nonerythroid spectrin αII (SPTAN1), abundant in the cuticular plate, surrounding the rootlets of stereocilia and along the plasma membrane. Interestingly, mice with HC-specific Sptan1 knockout exhibited rapid deafness, abnormal formation of stereocilia and cuticular plates, and loss of HCs from middle and apical turns of the cochlea during early postnatal stages. Additionally, Sptan1 deficiency led to the decreased spreading of House Ear Institute-Organ of Corti 1 cells, and induced abnormal formation of focal adhesions and integrin signaling in mouse HCs. Altogether, our findings highlight SPTAN1 as a critical molecule for HC stereocilia morphology and auditory function via regulation of focal adhesion signaling.

20.
Nanoscale ; 13(41): 17254-17271, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34651623

RESUMO

Angiogenesis is an essential process for tumor development. Owing to the imbalance between pro- and anti-angiogenic factors, the tumor vasculature possesses the characteristics of tortuous, hyperpermeable vessels and compressive force, resulting in a reduction in the effect of traditional chemotherapy and radiotherapy. Anti-angiogenesis has emerged as a promising strategy for cancer treatment. Tumor angiogenesis, however, has been proved to be a complex process in which the tumor microenvironment (TME) plays a vital role in the initiation and development of the tumor microvasculature. The host stromal cells in the TME, such as cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs) and Treg cells, contribute to angiogenesis. Furthermore, the abnormal metabolic environment, such as hypoxia and acidosis, leads to the up-regulated expression of angiogenic factors. Indeed, normalization of the tumor microvasculature via targeting and modulating the TME has become a promising strategy for anti-angiogenesis and anti-tumor therapy. In this review, we summarize the abnormalities of the tumor microvasculature, tumor angiogenesis induced by an abnormal metabolic environment and host stromal cells, as well as drug delivery therapies to restore the balance between pro- and anti-angiogenic factors by targeting and normalizing the tumor vasculature in the TME.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia , Microvasos , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico
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