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1.
Sensors (Basel) ; 23(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36679686

RESUMO

Shipborne atomic gravimeter (SAG) is an instrument that can directly measure absolute gravity in dynamic environments. As a new type of gravity sensor, a standard method for evaluating its detailed performance has not been proposed and the detailed performance of SAG was rarely reported. In this paper, a system of dynamic gravity measurement, which was integrated with a home-made atomic gravimeter, is demonstrated, and a novel and simple method for testing the performance of SAG on the lake based on the modulated Coriolis effect is put forward. Firstly, in the state of ship mooring, a tilt modulation of the gravity sensor has been realized to make sure the Raman wave vector is parallel to the gravity axis. Moreover, a comparison between the measurement result of CG-5 and SAG has also been carried out to evaluate the accuracy of the SAG. Then, the Coriolis effect modulating experiment is carried out with various routes on lake to test its performance in dynamic environments. In the ship mooring state, the accuracy has been demonstrated to be 0.643 mGal. The internal consistency reliabilities are evaluated to be 0.8 mGal and 1.2 mGal under the conditions of straight line and circle navigation, respectively.


Assuntos
Força Coriolis , Gravitação , Navios
2.
Future Med Chem ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651264

RESUMO

Aim: The clinical benefits of FLT3 inhibitors against acute myeloid leukemia (AML) have been limited by selectivity and resistance mutations. Thus, to identify FLT3 inhibitors possessing high selectivity and potency is of necessity. Methods & results: The authors used computational methods to systematically compare pocket similarity with 269 kinases. Subsequently, based on these investigations and beginning with in-house compound 10, they synthesized a series of 6-methyl-isoxazol[3,4-b]pyridine-3-amino derivatives and identified that compound 45 (IC50: 103 nM) displayed gratifying potency in human AML cell lines with FLT3-internal tandem duplications mutation as well as FLT3-internal tandem duplications-tyrosine kinase domain-transformed BaF3 cells. Conclusion: The integrated biological activity results indicated that compound 45 deserves further development for therapeutic remedies for AML.

3.
Nat Commun ; 14(1): 305, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658146

RESUMO

The applicability of nuclease-based form of prime editor (PEn) has been hindered by its complexed editing outcomes. A chemical inhibitor against DNA-PK, which mediates the nonhomologous end joining (NHEJ) pathway, was recently shown to promote precise insertions by PEn. Nevertheless, the intrinsic issues of specificity and toxicity for such a chemical approach necessitate development of alternative strategies. Here, we find that co-introduction of PEn and a NHEJ-restraining, 53BP1-inhibitory ubiquitin variant potently drives precise edits via mitigation of unintended edits, framing a high-activity editing platform (uPEn) apparently complementing the canonical PE. Further developments involve exploring the effective configuration of a homologous region-containing pegRNA (HR-pegRNA). Overall, uPEn can empower high-efficiency installation of insertions (38%), deletions (43%) and replacements (52%) in HEK293T cells. When compared with PE3/5max, uPEn demonstrates superior activities for typically refractory base substitutions, and for small-block edits. Collectively, this work establishes a highly efficient PE platform with broad application potential.


Assuntos
Quebras de DNA de Cadeia Dupla , Edição de Genes , Humanos , Células HEK293 , Reparo do DNA por Junção de Extremidades , Sistemas CRISPR-Cas
4.
Small ; : e2206819, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36592418

RESUMO

Slippery and transparent polyvinyl alcohol (PVA) hydrogels with mechanical robustness exhibit broad applications in artificial biological soft tissues, flexible wearable electronics, and implantable biomedical devices. Most of the current PVA hydrogels, however, are unable to integrate these features, which compromises its performance in biological and engineering applications. To achieve such purpose, herein, a novel tactic is proposed, salting-out-after-syneresis of PVA, to realize a mechanically robust and highly transparent slippery PVA hydrogel. The syneresis of PVA sol is first conducted to form highly dense and transparent PVA polymer networks, then the salting-out effect tunes the aggregation of the polymer chains to rapidly induce the phase separation and crystallization. The resultant hydrogels show the transparency up to 98% in the visible region, the tribological coefficient down to 0.0081, and the excellent mechanical properties with strength, modulus, and toughness of 26.72 ± 1.05, 6.66 ± 0.29 MPa, and 55.21 ± 1.62 MJ m-3 , respectively. To reveal the potentials, PVA contact lens that combine remarkable lubrication, anti-protein adhesion, biocompatibility, and drug-loading functions are demonstrated. This strategy provides a simple and new avenue for developing the mechanically robust, transparent, and hydrated hydrogels, showing the potential in biomedicine and wearable devices.

5.
J Cardiothorac Surg ; 18(1): 6, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609343

RESUMO

OBJECTIVE: Acute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD. METHODS: A total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI. RESULTS: In our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001]. CONCLUSIONS: Low preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.


Assuntos
Injúria Renal Aguda , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Obesidade/complicações , /cirurgia , Fibrinogênio
6.
Drug Dev Res ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36644989

RESUMO

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 µM. Besides, F15 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC50 = 253 nM) and MV4-11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.

7.
Microbiol Spectr ; : e0295522, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700635

RESUMO

The maternal gut microbiome affects the duration of pregnancy, delivery, and lactation. It also coordinates the stability of maternal metabolism by regulating and modulating inflammatory cytokines and reproductive hormones. This has been shown in several species; however, the situation in ruminants remains a black box. Here, we aimed to elucidate the relationship between the hindgut microbiota, metabolism, and reproductive hormones in domestic goats (Capra hircus) during nonpregnancy, pregnancy, and lactation stages. The hindgut microbiota was altered during these three stages, with a drastic decrease in the abundance of Family_XIII_AD3011_group in the second and third trimesters of pregnancy. Additionally, a decline in the abundance of Christensenellaceae_R-7_group and Turicibacter was observed from the nonpregnancy stage to late gestation. Family_XIII_AD3011_group and Paeniclostridium were strongly correlated with decreased fecal estradiol and progesterone. Furthermore, we generated a metabolome atlas of the gut and serum from nonpregnancy to lactation to reveal the specific metabolic fingerprints of each physiological stage. Several specific gut metabolites, including carnitine C8:1, γ-aminobutyric acid, and indole-3-carboxylic acid, were negatively correlated with the fecal and serum estradiol concentrations. In contrast, 2'-deoxyinosine, deoxyadenosine, and 5'-deoxyadenosine were positively correlated with the fecal and serum estradiol concentrations. The levels of 2'-deoxyinosine, deoxyadenosine, and 5'-deoxyadenosine in fecal samples were positively correlated with Family_XIII_AD3011_group. Other serum metabolites, such as (±)12-HEPE (hydroxy eicosapentaenoic acid), (±)15-HEPE, (±)18-HEPE, cytidine, uracil, and 5-hydroxyindole-3-acetic acid, were negatively correlated with the serum concentrations of estradiol and progesterone. Finally, Corynebacterium and Clostridium_sensu_stricto_1 in the fecal samples were positively correlated with the abundance of 11,12-EET (epoxy-eicosatrienoic acid), (±)18-HEPE, (±)15-HEPE, and (±)12-HEPE in the serum. IMPORTANCE Our findings revealed that the activity of Family_XIII_AD3011_group and Corynebacterium is strongly correlated with the beneficial regulation of physiological hormones and metabolic changes during pregnancy and lactation. These findings are key for guiding targeted microbial therapeutic approaches to modulate microbiomes in gestating and lactating mammals.

8.
Medicine (Baltimore) ; 102(1): e32637, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607872

RESUMO

Acute kidney injury (AKI) is a life-threatening complication of acute type A aortic dissection (ATAAD) patients. Increasing evidence suggests that histamine ameliorates the pathology of renal injury. However, data on the association between histamine levels and postoperative AKI in ATAAD patients are limited. The purpose of our study was to explore the incidence and independent risk factors of postoperative AKI, with special emphasis on the relationship between preoperative plasma histamine levels and the severity of postoperative ATAAD-AKI. This retrospective single-center study evaluated 160 patients with ATAAD admitted to the Beijing Anzhen Hospital aortic surgery database between April 2020 and December 2021. Univariate and multivariate logistic regression analyses were performed to determine the potential risk factors for postoperative ATAAD-AKI. A subgroup analysis was performed to investigate the association between preoperative plasma histamine levels and the severity of postoperative ATAAD-AKI or continuous renal replacement therapy (CRRT). ATAAD-AKI occurred in 84 of 160 patients (52.5%), including 32 with stage 1 (38.1%), 14 with stage 2 (16.7%), 38 with stage 3 (45.2%), and 34 (21.3%) received postoperative CRRT. The in-hospital mortality rate was 19.0% (16/84) in the AKI group and 2.6% (2/76) in the non-AKI group (P = .02). Preoperative lower plasma histamine levels (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.10-1.52; P = .004) were an important factor related to postoperative ATAAD-AKI in multivariate logistic regression analysis. Subgroup analysis revealed that low preoperative plasma histamine level was independently associated with postoperative ATAAD-AKI (stage 3) (OR, 1.38; 95% CI, 1.10-1.73; P = .005) and CRRT (OR, 1.44; 95% CI, 1.13-1.79; P = .008). Low preoperative plasma histamine level was an independent prognostic indicator of postoperative AKI in patients with ATAAD, especially for postoperative AKI (stage 3) and CRRT. Preoperative plasma histamine levels may serve as potential protective biomarkers of postoperative ATAAD-AKI.


Assuntos
Injúria Renal Aguda , Histamina , Humanos , Estudos Retrospectivos , Biomarcadores , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Complicações Pós-Operatórias/epidemiologia
9.
Biofabrication ; 15(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36626826

RESUMO

While current clinical utilization of large vascular grafts for vascular transplantation is encouraging, tissue engineering of small grafts still faces numerous challenges. This study aims to investigate the feasibility of constructing a small vascular graft from decellularized amniotic membranes (DAMs). DAMs were rolled around a catheter and each of the resulting grafts was crosslinked with (a) 0.1% glutaraldehyde; (b) 1-ethyl-3-(3-dimethylaminopropyl) crbodiimidehydro-chloride (20 mM)-N-hydroxy-succinimide (10 mM); (c) 0.5% genipin; and (d) no-crosslinking, respectively. Our results demonstrated the feasibility of using a rolling technique followed by lyophilization to transform DAM into a vessel-like structure. The genipin-crosslinked DAM graft showed an improved integrated structure, prolonged stability, proper mechanical property, and superior biocompatibility. After transplantation in rat abdominal aorta, the genipin-crosslinked DAM graft remained patent up to 16 months, with both endothelial and smooth muscle cell regeneration, which suggests that the genipin-crosslinked DAM graft has great potential to beimplementedas a small tissue engineered graft for futurevasculartransplantation.

10.
Physiol Behav ; 260: 114056, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36528127

RESUMO

The microbiota-gut-brain axis is a bidirectional regulatory pathway between the brain and the gastrointestinal tract, which plays an important role in maintain homeostasis. Gut microbiota could influence the behavior, cognition, stress response and others via the axis. Depression is a complex psychiatric disease, giving rise to heavy social health and economic burden. In recent years, studies have shown that the gut microbiota are closely linked to the pathophysiological processes of depression. In this article, the interaction and its underlying mechanisms between depression and gut microbiota were summarized.


Assuntos
Depressão , Microbioma Gastrointestinal , Humanos , Depressão/etiologia , Eixo Encéfalo-Intestino , Encéfalo/metabolismo , Microbioma Gastrointestinal/fisiologia , Cognição
11.
Food Res Int ; 162(Pt A): 111939, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461195

RESUMO

Deoxynivalenol (DON) is one of the most widely distributed and toxicologically dangerous mycotoxins. Cold atmospheric plasma (CAP) experiments have indicated a considerable degrading effect on DON, but the underlying interaction mechanism of plasma species and DON remains unknown. In this paper, a Reactive Molecular Dynamics (RMD) simulation is carried out to investigate the DON detoxification pathways induced by reactive oxygen species (ROS). The simulation results indicate that the given ROS (O atoms, OH radicals, H2O2 molecules, and O3 molecules) can modify toxicologically important functional groups through the processes of the ring-opening reaction of the 12,13-epoxide ring and the scission of double C9 = C10 bond to reduce the toxicity of DON. The formation of aldehyde and ketone groups by the hydrogen atom abstraction reaction can also be observed in the simulation, which agrees well with the experimental measurements. Furthermore, the dose effects described by the number density of ROS are examined to provide experimental guidance on plasma discharge parameter settings. The chemical pathways and statistical data reveal DON's atomic-scale degradation mechanism and give a theoretical understanding of the optimal strategy for degrading mycotoxins in future applications.


Assuntos
Micotoxinas , Gases em Plasma , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Simulação de Dinâmica Molecular , Oxigênio
12.
Artif Intell Med ; 134: 102440, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36462902

RESUMO

Medical event prediction (MEP) is a fundamental task in the healthcare domain, which needs to predict medical events, including medications, diagnosis codes, laboratory tests, procedures, outcomes, and so on, according to historical medical records of patients. Many researchers have tried to build MEP models to overcome the challenges caused by the heterogeneous and irregular temporal characteristics of EHR data. However, most of them consider the heterogenous and temporal medical events separately and ignore the correlations among different types of medical events, especially relations between heterogeneous historical medical events and target medical events. In this paper, we propose a novel neural network based on attention mechanism called Cross-event Attention-based Time-aware Network (CATNet) for MEP. It is a time-aware, event-aware and task-adaptive method with the following advantages: 1) modeling heterogeneous information and temporal information in a unified way and considering irregular temporal characteristics locally and globally respectively, 2) taking full advantage of correlations among different types of events via cross-event attention. Experiments on two public datasets (MIMIC-III and eICU) show CATNet outperforms other state-of-the-art methods on various MEP tasks. The source code of CATNet is released at https://github.com/sherry6247/CATNet.git.


Assuntos
Redes Neurais de Computação , Software , Humanos
13.
Front Microbiol ; 13: 1064363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466694

RESUMO

Background: The soil fungal community is one of the most important drivers of the soil nutrient cycling that sustains plant growth. However, little research has been done on the effects of different land uses on soil fungal communities in northeast China. Methods: In this study, we conducted a field experiment to investigate the effects of continuous cropping of grass, maize, and alfalfa on their respective fungal communities and co-occurrence networks. Results: We showed that the physicochemical properties of the soil, such as nitrate (NO 3 - N), available phosphorus, and soil pH, were the most important driving factors affecting the structure of the soil fungal community in different cropping systems. In addition, compared to the cultivation of grass and maize, the continuous cropping of alfalfa increased the abundance of several beneficial as well as pathogenic species, such as Mortierella and Gaiellales. In addition, the networks differed among plant species and according to the number of years of continuous cultivation. Conclusion: This suggests that the continuous cropping of alfalfa results in greater cooperation among fungi, which may be beneficial to the soil as well as to the development of the alfalfa.

14.
Pharmaceutics ; 14(12)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36559082

RESUMO

Three-dimensional (3D) printing is an additive manufacturing technique that creates objects under computer control. Owing to the rapid advancement of science and technology, 3D printing technology has been widely utilized in processing and manufacturing but rarely used in the pharmaceutical field. The first commercial form of Spritam® immediate-release tablet was approved by FDA in 2015, which promoted the advancement of 3D printing technology in pharmaceutical development. Three-dimensional printing technology is able to meet individual treatment demands with customized size, shape, and release rate, which overcomes the difficulties of traditional pharmaceutical technology. This paper intends to discuss the critical process parameters of binder jet 3D printing technology, list its application in pharmaceutical manufacturing in recent years, summarize the still-open questions, and demonstrate its great potential in the pharmaceutical industry.

15.
Opt Express ; 30(26): 46209-46226, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558580

RESUMO

Optical beams carrying orbital angular momentum (OAM) have received much attention due to the prospects of their use in terahertz communications, biomedical engineering, and imaging. Here we propose an antenna design for the generation of multiple beams carrying OAM with different topological states at the same frequency. The proposed OAM generator is based on a compact set of microstrip ring-shaped resonators. An analytical solution for the radiated field of a single circular ring resonator antenna is derived involving the cavity model and the magnetic current approach. To verify our theoretical description, the numerical full-wave simulation is performed for an actual size OAM generator with the use of the ANSYS HFSS electromagnetic solver, and an antenna prototype operating in the microwave band is fabricated and tested. Conditions of the antenna operation in the combined OAM and mode-division multiplexing (OAM-MDM) regimes are discussed. Obtained results prove that the proposed antenna can be used as a compact and low-cost generator of multiple beams with different OAM states.

16.
J Int Med Res ; 50(12): 3000605221138481, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36476062

RESUMO

OBJECTIVE: The treatment and incidence of femoral neck fracture (FNF) in older patients is controversial. We investigated the new AO (Arbeitsgemeinschaft für Osteosynthese) classification in patients with FNF by age to determine the proportions of stable fracture and change trends according to patients' age. METHODS: We divided patients with FNF hospitalized in Xi'an Honghui Hospital from 2018 to 2020 into five groups according to age: young (<50 years), middle-aged (50-59 years), young-elderly (60-69 years), middle-elderly (70-79 years), and very elderly (≥80 years) groups. We retrospectively collected data of patients' sex, admission date, fracture side, mechanism of injury, and new AO classification. RESULTS: In total, 2071 patients were included for analysis, with 1329 women (64.2%); 1106 patients (53.4%) had left-side fracture. The main mechanism of injury was falling. In the young-elderly, middle-elderly, and very-elderly groups, 33.3%, 29.2%, and 24.1% had stable fracture type, respectively). The proportion of patients with FNF did not show a change trend by age during the 3-year investigation period. CONCLUSION: In our study, the proportion of older patients with FNF did not increase, and as many as a third of patients with FNF aged 50 to 70 years had stable fracture.


Assuntos
Fraturas do Colo Femoral , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Fraturas do Colo Femoral/epidemiologia , Fraturas do Colo Femoral/cirurgia , Estudos Retrospectivos
17.
ACS Omega ; 7(49): 44620-44630, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36530248

RESUMO

The huge energy penalty of CO2 desorption is the greatest challenge impeding the commercial application of amine-based CO2 capture. To deal with this problem, a series of metal oxide and oxyhydroxide catalysts were synthesized in this study to kinetically facilitate the CO2 desorption from 5.0 M monoethanolamine (MEA). The effects of selected catalysts on CO2 absorption kinetics, CO2 absorption capacity, CO2 reaction enthalpy, and desorption duty reduction of 2.0 M MEA were investigated by a true heat flow reaction calorimeter to access the practical feasibility of the catalytic CO2 desorption. The kinetic study of catalytic CO2 desorption was also carried out. CO2 desorption chemistry, catalyst characterization, and structure-function relationships were investigated to reveal the underlying mechanisms. Results show that addition of the catalyst had slight effects on the CO2 absorption kinetics and CO2 reaction enthalpy of MEA. In contrast, the CO2 desorption efficiency greatly increased from 28% in reference MEA to 52% in ZrO(OH)2-aided MEA. Compared to the benchmark catalyst HZSM-5, ZrO(OH)2 exhibited a 13% improvement in CO2 desorption efficiency. More importantly, compared to the reference MEA, the CO2 desorption duties of ZrO(OH)2 and FeOOH-aided MEA significantly reduced by 45 and 47% respectively, which are better than those of most other reported catalysts. The large surface area, pore volume, pore diameter, and amount of surface hydroxyl groups of ZrO(OH)2 and FeOOH afforded the catalytic performance by promoting the adsorption of alkaline speciation (e.g., MEA and HCO3 -) onto the particle surface.

18.
Front Psychol ; 13: 989380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518950

RESUMO

From the perspective of social information processing theory and social identity theory, 1,267 employees were selected as the subjects, and the data were statistically analyzed by using Mplus8.0 and SPSS25.0 to explore the relationship between positive workplace gossip and job satisfaction and the role of job insecurity and organizational identity in this relationship. The results showed that there was a significant positive correlation between positive workplace gossip and job satisfaction. Furthermore, job insecurity and organizational identity independently mediated the relationship between positive workplace gossip and employee job satisfaction. In addition, job insecurity and organizational identity played a serial mediating role in the relationship between positive workplace gossip and job satisfaction. The results of the study shed light on how job insecurity and organizational identity were associated with the process of the positive workplace gossip-job satisfaction relationship. Based on the findings, implications and avenues for future research were discussed.

19.
BMC Microbiol ; 22(1): 273, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368924

RESUMO

BACKGROUND: Myostatin (MSTN) negatively regulates the muscle growth in animals and MSTN deficient sheep have been widely reported previously. The goal of this study was to explore how MSTN inactivation influences their gut microbiota composition and potential functions. RESULTS: We compared the slaughter parameters and meat quality of 3 MSTN-edited male sheep and 3 wild-type male sheep, and analyzed the gut microbiome of the MSTN-edited sheep (8 female and 8 male sheep) and wild-type sheep (8 female and 8 male sheep) through metagenomic sequencing. The results showed that the body weight, carcass weight and eye muscle area of MSTN-edited sheep were significantly higher, but there were no significant differences in the meat quality indexes. At the microbial level, the alpha diversity was significantly higher in the MSTN-edited sheep (P < 0.05), and the microbial composition was significantly different by PCoA analysis in the MSTN-edited and wild-type sheep. The abundance of Firmicutes significantly increased and Bacteroidota significantly decreased in the MSTN-edited sheep. At genus level, the abundance of Flavonifractor, Subdoligranulum, Ruthenibacterium, Agathobaculum, Anaerotignum, Oribacterium and Lactobacillus were significantly increased in the MSTN-edited sheep (P < 0.05). Further analysis of functional differences was found that the carotenoid biosynthesis was significantly increased and the peroxisome, apoptosis, ferroptosis, N-glycan biosynthesis, thermogenesis, and adipocytokines pathways were decreased in the MSTN-edited sheep (P < 0.05). Moreover, carbohydrate-active enzymes (CAZymes) results certified the abundance of the GH13_39, GH4, GH137, GH71 and PL17 were upregulated, and the GT41 and CBM20 were downregulated in the MSTN-edited sheep (P < 0.05). CONCLUSIONS: Our study suggested that MSTN inactivation remarkably influenced the composition and potential function of hindgut microbial communities of the sheep, and significantly promoted growth performance without affecting meat quality.


Assuntos
Microbioma Gastrointestinal , Miostatina , Ovinos , Masculino , Feminino , Animais , Miostatina/genética , Carne , Expressão Gênica
20.
Hum Cell ; 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36403174

RESUMO

Breast cancer is the most prevalent cancer, and it is accompanied by high heterogeneity. N6-methyladenosine (m6A) modification significantly contributes to breast cancer tumorigenesis and progression. However, how m6A-related genes affect the clinical outcomes and tumor immune microenvironment (TIME) of breast cancer is largely unknown. Our study developed an m6A-related gene signature on the basis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The m6A-related gene signature was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Breast cancer patients were classified into low- and high-risk groups depending on the median risk score. The reliability and efficiency of the signature were validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA). The risk score was validated as an independent indicator associated with overall survival, and a nomogram model was created to estimate the overall survival of patients with breast cancer. Functional annotation suggested that the risk score had a strong relationship with immune-related pathways. Different proportions of immune cell infiltration between the two groups were evaluated using various algorithms. The high-risk group had higher immune checkpoint expression levels. We discovered that one of the 6 prognostic genes, TMEM71, was downregulated in breast cancer tissues. In vitro experiments indicated that overexpression of TMEM71 suppressed breast cancer cell proliferation and migration. In conclusion, the m6A-related gene signature may be a sensitive biomarker for overall survival prediction and guide the individualized treatment for breast cancer patients.

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