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1.
Ann Med ; 53(1): 1722-1726, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34596490

RESUMO

OBJECTIVE: Low triiodothyronine syndrome (LT3S) is a common endocrine disease in preterm neonates. Various serious acute or chronic diseases result in LT3S. Few studies have investigated the causal relationship between perinatal factors and LT3S in preterm neonates with a gestational age (GA) of 28-35 weeks. The present study comprehensively analyzed the perinatal factors of LT3S in preterm neonates. METHODS: This was a retrospective study of neonates with and without LT3S from January 2018 to November 2019. Compared to 206 preterm neonates without LT3S, 158 neonates were diagnosed with LT3S, excluding neonates with congenital malformations, other endocrine diseases, genetic diseases and inherited metabolic diseases. RESULTS: Five perinatal risk factors for LT3S were confirmed using univariate and multivariate analyses: smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), neonatal sepsis, and dopamine use. CONCLUSIONS: LT3S in preterm neonates was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, RDS, sepsis, and dopamine use. Preterm neonates with a GA of 28-35 weeks who are exposed to a series of high-risk perinatal factors must be closely observed, diagnosed early and treated for primary diseases promptly to reduce the occurrence of LT3S and improve the outcomes.Key Message:Few studies have investigated the relationship between perinatal factors and Low triiodothyronine syndrome (LT3S) in preterm neonates with a gestational age (GA) of 28-35 weeks.LT3S was associated with multiple perinatal factors, including smaller gestational age, lower birth weight, respiratory distress syndrome (RDS), sepsis, and dopamine use.

2.
Eur J Med Chem ; 226: 113870, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34610548

RESUMO

Concomitant inhibition of estrogen receptor alpha (ERα) and histone deacetylase (HDAC) signaling has been proven effective in endocrine-resistant ER+ breast cancers. Herein, a series of tetrahydroisoquinoline (THIQ)-hydroxamate conjugates were rationally designed and synthesized as dual SERDs/HDAC inhibitors by incorporating the hydroxamate, a known HDAC pharmacophore, into a privileged THIQ scaffold of selective ERα degraders (SERDs). Some of these THIQ-hydroxamate conjugates displayed remarkable HDAC6 inhibition and improved antiproliferative activity against MCF-7 cells. Particularly, the most potent HDAC inhibitor 19k also exhibits potent ERα binding affinity, good ERα degradation efficacy and the best antiproliferative activity. Besides, 19k displayed superior antitumor efficacy than the drug combination (Fulvestrant + SAHA) through promoting ERα degradation and histone acetylation in an MCF-7 xenograft model, without causing observable toxicity. Collectively, this study validates the therapeutic potential of a dual-acting compound with potent ERα degradation efficacy and HDAC6 inhibition in breast cancer.

3.
Eur J Med Chem ; 226: 113887, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34624824

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early diagnosis is the key to treatment but is still a great challenge in the clinic now. The discovery of alpha-synuclein (α-syn) aggregates ligands has become an attractive strategy to meet the early diagnosis of PD. Herein, we designed and synthesized a series of styrylaniline derivatives as novel α-syn aggregates ligands. Several compounds displayed good potency to α-syn aggregates with Kd values less than 0.1 µM. The docking study revealed that the hydrogen bonds and cation-pi interaction between ligands and α-syn aggregates would be crucial for the activity. The representative compound 7-16 not only detected α-syn aggregates in both SH-SY5Y cells and brain tissues prepared from two kinds of α-syn preformed-fibrils-injected mice models but also showed good blood-brain barrier penetration characteristics in vivo with a brain/plasma ratio over 1.0, which demonstrates its potential as a lead compound for further development of in vivo imaging agents.

4.
Eur J Clin Nutr ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584226

RESUMO

BACKGROUND: Anthropometric measurements (AMs) are cost-effective surrogates for evaluating body size. This study aimed to identify the optimal prognostic AMs, their thresholds, and their joint associations with cancer mortality. METHODS: We performed an observational cohort study including 12138 patients with cancer at five institutions in China. Information on demographics, disease, nutritional status, and AMs, including the body mass index, mid-arm muscle circumference, mid-arm circumference, handgrip strength, calf circumference (CC), and triceps-skinfold thickness (TSF), was collected and screened as mortality predictors. The optimal stratification was used to determine the thresholds to categorize those prognostic AMs, and their associations with mortality were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HRs). RESULTS: The study included 5744 females and 6394 males with a mean age of 56.9 years. The CC and TSF were identified as better mortality predictors than other AMs. The optimal thresholds were women 30 cm and men 32.8 cm for the CC, and women 21.8 mm and men 13.6 mm for the TSF. Patients in the low CC or low TSF group had a 13% (HR = 1.13, 95% CI = 1.03-1.23) and 22% (HR = 1.22, 95% CI = 1.12-1.32) greater mortality risk compared with their normal CC/TSF counterparties, respectively. Concurrent low CC and low TSF showed potential joint effect on mortality risk (HR = 1.39, 95% CI = 1.25-1.55). CONCLUSIONS: These findings support the importance of assessing the CC and TSF simultaneously in hospitalized cancer patients to guide interventions to optimize their long-term outcomes.

5.
BMJ Open ; 11(9): e047227, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493510

RESUMO

OBJECTIVE: To evaluate epidemiological characteristics and transmission dynamics of COVID-19 outbreak resurged in Beijing and to assess the effects of three non-pharmaceutical interventions. DESIGN: Descriptive and modelling study based on surveillance data of COVID-19 in Beijing. SETTING: Outbreak in Beijing. PARTICIPANTS: The database included 335 confirmed cases of COVID-19. METHODS: To conduct spatiotemporal analyses of the outbreak, we collected individual records on laboratory-confirmed cases of COVID-19 from 11 June 2020 to 5 July 2020 in Beijing, and visitor flow and products transportation data of Xinfadi Wholesale Market. We also built a modified susceptible-exposed-infected-removed model to investigate the effect of interventions deployed in Beijing. RESULTS: We found that the staff working in the market (52.2%) and the people around 10 km to this epicentre (72.5%) were most affected, and the population mobility entering-exiting Xinfadi Wholesale Market significantly contributed to the spread of COVID-19 (p=0.021), but goods flow of the market had little impact on the virus spread (p=0.184). The prompt identification of Xinfadi Wholesale Market as the infection source could have avoided a total of 25 708 (95% CI 13 657 to 40 625) cases if unnoticed transmission lasted for a month. Based on the model, we found that active screening on targeted population by nucleic acid testing alone had the most significant effect. CONCLUSIONS: The non-pharmaceutical interventions deployed in Beijing, including localised lockdown, close-contact tracing and community-based testing, were proved to be effective enough to contain the outbreak. Beijing has achieved an optimal balance between epidemic containment and economic protection.


Assuntos
COVID-19 , Pequim/epidemiologia , China/epidemiologia , Controle de Doenças Transmissíveis , Surtos de Doenças , Humanos , SARS-CoV-2
6.
Int J Hyperthermia ; 38(1): 1359-1365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34505553

RESUMO

OBJECTIVE: This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart. METHOD: The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated. RESULTS: The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40-140 min), and mean follow-up time was 31.5 ± 22.2 months (6-92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively. CONCLUSION: MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.


Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos , Resultado do Tratamento
7.
Int Immunopharmacol ; 100: 108092, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474272

RESUMO

Indole- and hydantoin-based derivatives both exhibit anti-inflammatory activity, suggesting that the structures of indole and hydantoin are functional for this activity. In the present study, we synthesized two types of indole-hydantoin derivatives, IH-1 (5-(1H-indole-3-ylmethylene) imidazolidine-2,4-dione) and IH-2 (5-(1H-indole-3-ylmethyl) imidazolidine-2,4-dione) and examined their effects on LPS-induced inflammatory responses in murine macrophage-like RAW264.7 cells. LPS-induced inflammatory responses were not affected by indole, hydantoin, or IH-2. In contrast, IH-1 significantly inhibited the LPS-induced production of nitric oxide (NO) and secretion of CCL2 and CXCL1 by suppressing the mRNA expression of inducible NO synthase (iNOS), CCL2, and CXCL1. IH-1 markedly inhibited the LPS-induced activation of NF-κB without affecting the degradation of IκBα or nuclear translocation of NF-κB. IH-1 markedly attenuated the transcriptional activity of NF-κB by suppressing the LPS-induced phosphorylation of the NF-κB p65 subunit at Ser276. Furthermore, IH-1 prevented the LPS-induced interaction of NF-κB p65 subunit with a transcriptional coactivator, cAMP response element-binding protein (CBP). Collectively, these results revealed the potential of the novel indole-hydantoin derivative, IH-1 as an anti-inflammatory drug.

8.
Environ Res ; 204(Pt A): 112032, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516980

RESUMO

A novel FeVO4/BiVO4 heterojunction photocatalyst was synthesized by hydrothermal method. The FeVO4/BiVO4 nanostructures were characterized by XRD, SEM, XPS, UV-vis, and photoluminescence spectroscopy. The effects of catalyst dosage, contaminant concentration, initial hydrogen peroxide (H2O2) concentration, and pH value on the degradation of levofloxacin were investigated and several repeated experiments were conducted to evaluate the stability and reproducibility. The optimized process parameters were used for mineralization experiments. Reactive oxygen species, degradation intermediates, and possible catalytic mechanisms were also investigated. The results showed that the sonophotocatalytic performance of the FeVO4/BiVO4 heterojunction catalyst was better than that of sonocatalysis and photocatalysis. In addition, the Type II heterojunction formed by the material still had good stability in the degradation of levofloxacin after 5 cycles. The possible degradation pathway and mechanism of levofloxacin by sonophotocatalysis were put forward. This work develops new sono-photo hybrid process for potential application in the field of wastewater treatment.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 889-895, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535202

RESUMO

OBJECTIVES: To investigate the incidence of maternal group B Streptococcus (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. METHODS: A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization. RESULTS: In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (P<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), P<0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (P<0.05), while adequate IAP was a protective factor (P<0.05) in the offspring of pregnant women with GBS colonization. CONCLUSIONS: GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. Citation.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibioticoprofilaxia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae
10.
11.
Nat Commun ; 12(1): 5641, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561436

RESUMO

An epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well established, but whether this reflects a shared genetic aetiology, and whether consistent genetic relationships exist between MS and the two predominant IBD subtypes, ulcerative colitis (UC) and Crohn's disease (CD), remains unclear. Here, we use large-scale genome-wide association study summary data to investigate the shared genetic architecture between MS and IBD overall and UC and CD independently. We find a significantly greater genetic correlation between MS and UC than between MS and CD, and identify three SNPs shared between MS and IBD (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672) in cross-trait meta-analyses. We find suggestive evidence for a causal effect of MS on UC and IBD using Mendelian randomization, but no or weak and inconsistent evidence for a causal effect of IBD or UC on MS. We observe largely consistent patterns of tissue-specific heritability enrichment for MS and IBDs in lung, spleen, whole blood and small intestine, and identify cell-type-specific enrichment for MS and IBDs in CD4+ T cells in lung and CD8+ cytotoxic T cells in lung and spleen. Our study sheds light on the biological basis of comorbidity between MS and IBD.

12.
Microb Pathog ; 159: 105124, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34364978

RESUMO

OBJECTIVES: Pseudomonas aeruginosa is a medically important pathogen showing intrinsic low permeability to various antimicrobial agents and its potential to acquire multiple resistance mechanism. A longitudinal surveillance aimed to investigate the antimicrobial resistance and its determinants of Pseudomonas aeruginosa in Southern China. A total of 2163 P. aeruginosa isolates were obtained from patients in Southern China during 2004-2016. METHODS: The antimicrobial susceptibility of the isolates was performed by disk diffusion and Vitek 2 automated system and interpreted according to the Clinical and Laboratory Standard Institute (CLSI) 2015. RESULTS: A significant downtrend of resistant rate (>10.0%) was observed for tested antibiotic agents including ciprofloxacin (>30.0%), gentamicin (29.0%), tobramycin (24.2%) and ceftazidime (24.0%) except for aztreonam and amikacin. A total of 269 randomly selected isolates were further studied on the carriage of ß-lactam resistance genes by using 7 groups of multiplex PCRs targeting on 20 genes. ß-lactam resistance genes were rarely detected with a rate lower than 8%. Among all ß-lactam resistance genes, blaSHV acquired the highest identification rate (18/269, 6.7%), followed by blaOXA-1-like (6/269, 2.2%) and blaPER (6/269, 2.2%). In addition, 8 different plasmid replicons were amplified using 8 groups of multiplex PCRs including 18 sets of primers. Only five plasmid replicons were identified in 5 different P. aeruginosa isolates. Insignificant clonal relatedness among the positive strains identified by regular PCR were further verified by randomly amplified polymorphic DNA (RAPD)-PCR. CONCLUSION: This study has provided comprehensive knowledge on current antimicrobial resistance, ß-lactam resistance genes and plasmid replicons carriage in a large scale of clinical P. aeruginosa isolates.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Replicon , beta-Lactamases/genética
13.
Med Sci Monit ; 27: e931162, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453030

RESUMO

BACKGROUND This multiple-center retrospective study aimed to investigate computed tomography (CT) imaging findings in 72 patients with airway-invasive pulmonary aspergillosis. MATERIAL AND METHODS Seventy-two patients with airway-invasive pulmonary aspergillosis confirmed by pathology results were divided into 3 types according to image characteristics. Type I involved the trachea or the main bronchus. Type II involved the lobular and segmental bronchi, which manifested early as bronchial wall thickening, and later development was divided into types IIa and IIb. Type IIa manifested as bronchiectasis, and type IIb manifested as consolidation around the bronchus. Type III involved the bronchioles and pulmonary parenchyma, with tree-in-bud sign and acinar nodules around. CT signs of the various types and their differentiation were investigated. RESULTS The main clinical manifestations of the 72 patients with airway-invasive pulmonary aspergillosis were shortness of breath (55/72, 76.4%), cough (40/72, 55.6%), expectoration (35/72, 48.6%), dyspnea (8/72, 11.1%), weight loss (2/72, 2.8%), and fever (30/72, 41.7%). CT typing identified 3 types: 2 patients (2.8%) had type I, presenting as thickening of trachea or main bronchial walls; 3 patients (4.2%) had early type II, manifesting as thickening of lobular or segmental bronchial walls; 27 patients (37.5%) developed type IIa, manifesting as bronchiectasis; 22 patients (30.6%) had type IIb, manifesting as consolidation around the bronchus; and 18 patients (25.0%) had type III, presenting as nodules and patchy shadows with small cavities in the periphery of the lung. CONCLUSIONS Airway pulmonary aspergillosis has characteristic imaging findings, which can help early clinical diagnosis through classification according to CT imaging characteristics.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/classificação , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Aspergilose Pulmonar Invasiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
14.
Curr Psychol ; : 1-10, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34334986

RESUMO

Panic buying is a globally witnessed behavior during the outbreak of COVID-19. This consumer behavior is related to many undesirable consequences, ranging from disrupting economic stability to hindering timely provision of supplies to those in dire need. As such, to understand the causes and underlying mechanisms of panic buying is crucial. Based on terror management theory, this study examined the contribution of perceived risk, social media use, and connection with close others to panic buying. Data were collected through an online survey from 972 Chinese citizens (65.9% female, M age = 33.69 years) at the beginning period of COVID-19 in early February 2020. The results found that individuals with a higher level of perceived risk were more prone to engage in panic buying, but this link was mitigated by connection with close others when individuals less used social media. Theoretically, this study advances the understandings of the psychological processes of panic buying during health crisis. Practically, alleviating individuals' perceived risk, establishing a healthy habit of social media use, and strengthening social ties are important to circumventing panic buying in times of COVID-19.

15.
Rice (N Y) ; 14(1): 71, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342723

RESUMO

BACKGROUND: Photo-thermo-sensitive genic male sterile (PTGMS) rice (Oryza sativa L.) is usually considered two-line male sterile rice because of its dual-purpose in two-line hybrid rice system: under short days and low temperatures, it is fertile and used for self-propagation, but under long days and high temperatures, it is sterile and used for hybrid seed production. Therefore, photoperiod and temperature conditions are extremely important for the fertility transition of two-line male sterile rice. In recent years, there have been frequent occurrences of abnormally low-temperature (ALT) resulting in failure of two-line hybrid rice seed production. The daily average temperature (DAT) during ALT events is sometimes higher than the critical sterility-inducing temperature (CSIT) of two-line male sterile rice, of which the night temperature is lower than the CSIT. DAT has been traditionally used as the single indicator of pollen fertility transition, but it is unknown why the fertility of two-line male sterile rice in seed production restored fertility under ALT conditions. RESULTS: For Hang93S (H93S), a newly released PTGMS line, we hypothesized fertility transition is determined mainly by the cumulative effective low temperature (ELT) and only a certain duration of low temperature is required every day during the fertility-sensitive period. This study simulated ALTs where the DAT was higher than the CSIT while some segments of night temperature were lower than the CSIT. The results showed H93S exhibited a fertility transition to varying degrees. Moreover, fertility was restored under simulated ALT conditions and pollen fertility increased with increasing cumulative ELT, indicating that the fertility transition was affected primarily by the cumulative ELT. Results also indicated that pollen fertility increased as the number of treatment days increased. CONCLUSIONS: The fertility transition is caused mainly by the cumulative ELT. In two-line male sterile rice breeding, the effects of day length, ALT at night, and continuous response days should be considered together. The present study provides new insight into fertility transition so breeders can more effectively utilize the two-line male sterile rice, H93S, in breeding programs.

16.
Nano Lett ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369776

RESUMO

Electrochemical CO2 reduction provides a promising strategy to product value-added fuels and chemical feedstocks. However, it remains a grand challenge to further reduce the overpotentials and increase current density for large-scale applications. Here, spontaneously Sn doped Bi/BiOx nanowires (denoted as Bi/Bi(Sn)Ox NWs) with a core-shell structure were synthesized by an electrochemical dealloying strategy. The Bi/Bi(Sn)Ox NWs exhibit impressive formate selectivity over 92% from -0.5 to -0.9 V versus reversible hydrogen electrode (RHE) and achieve a current density of 301.4 mA cm-2 at -1.0 V vs RHE. In-situ Raman spectroscopy and theoretical calculations reveal that the introduction of Sn atoms into BiOx species can promote the stabilization of the *OCHO intermediate on the Bi(Sn)Ox surface and suppress the competitive H2/CO production. This work provides effective in situ construction of the metal/metal oxide hybrid composites with heteroatom doping and new insights in promoting electrochemical CO2 conversion into formate for practical applications.

17.
Clin Nutr ; 40(8): 4958-4970, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358843

RESUMO

BACKGROUND AND AIMS: Most nutritional assessment tools are based on pre-defined questionnaires or consensus guidelines. However, it has been postulated that population data can be used directly to develop a solution for assessing malnutrition. This study established a machine learning (ML)-based, individualized decision system to identify and grade malnutrition using large-scale data from cancer patients. METHODS: This was an observational, nationwide, multicenter cohort study that included 14134 cancer patients from five institutions in four different geographic regions of China. Multi-stage K-means clustering was performed to isolate and grade malnutrition based on 17 core nutritional features. The effectiveness of the identified clusters for reflecting clinical characteristics, nutritional status and patient outcomes was comprehensively evaluated. The study population was randomly split for model derivation and validation. Multiple ML algorithms were developed, validated and compared to screen for optimal models to implement the cluster prediction. RESULTS: A well-nourished cluster (n = 8193, 58.0%) and a malnourished cluster with three phenotype-specific severity levels (mild = 2195, 15.5%; moderate = 2491, 17.6%; severe = 1255, 8.9%) were identified. The clusters showed moderate agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria. The severity of malnutrition was negatively associated with the nutritional status, physical status, quality of life, and short-term outcomes, and was monotonically correlated with reduced overall survival. A multinomial logistic regression was found to be the optimal ML algorithm, and models built based on this algorithm showed almost perfect performance to predict the clusters in the validation data. CONCLUSIONS: This study developed a fusion decision system that can be used to facilitate the identification and severity grading of malnutrition in patients with cancer. Moreover, the study workflow is flexible, and might provide a generalizable solution for the artificial intelligence-based assessment of malnutrition in a wider variety of scenarios.

18.
BMC Genomics ; 22(1): 621, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404356

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP. METHODS: The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs. RESULTS: A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively. CONCLUSIONS: LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.


Assuntos
RNA Longo não Codificante , Morte Súbita Inesperada na Epilepsia , Animais , Tronco Encefálico , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos DBA , RNA Longo não Codificante/genética
19.
EBioMedicine ; 69: 103463, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34224973

RESUMO

BACKGROUND: Family with Sequence Similarity 13, Member A (FAM13A) gene has been consistently associated with COPD by Genome-wide association studies (GWAS). Our previous study demonstrated that FAM13A was mainly expressed in the lung epithelial progenitors including Club cells and alveolar type II epithelial (ATII) cells. Fam13a-/- mice were resistant to cigarette smoke (CS)-induced emphysema through promoting ß-catenin/Wnt activation. Given the important roles of ß-catenin/Wnt activation in alveolar regeneration during injury, it is unclear when and where FAM13A regulates the Wnt pathway, the requisite pathway for alveolar epithelial repair, in vivo during CS exposure in lung epithelial progenitors. METHODS: Fam13a+/+ or Fam13a-/- mice were crossed with TCF/Lef:H2B-GFP Wnt-signaling reporter mouse line to indicate ß-catenin/Wnt-activated cells labeled with GFP followed by acute (1 month) or chronic (7 months) CS exposure. Fluorescence-activated flow cytometry analysis, immunofluorescence and organoid culture system were performed to identify the ß-catenin/Wnt-activated cells in Fam13a+/+ or Fam13a-/- mice exposed to CS. Fam13a;SftpcCreERT2;Rosa26RmTmG mouse line, where GFP labels ATII cells, was generated for alveolar organoid culture followed by analyses of organoid number, immunofluorescence and gene expression. Single cell RNA-seq data from COPD ever smokers and nonsmoker control lungs were further analyzed. FINDINGS: We found that FAM13A-deficiency significantly increased Wnt activation mainly in lung epithelial cells. Consistently, after long-term CS exposure in vivo, FAM13A deficiency bestows alveolar epithelial progenitor cells with enhanced proliferation and differentiation in the ex vivo organoid model. Importantly, expression of FAM13A is significantly increased in human COPD-derived ATII cells compared to healthy ATII cells as suggested by single cell RNA-sequencing data. INTERPRETATION: Our findings suggest that FAM13A-deficiency promotes the Wnt pathway-mediated ATII cell repair/regeneration, and thereby possibly mitigating CS-induced alveolar destruction. FUND: This project is funded by the National Institutes of Health of United States of America (NIH) grants R01HL127200, R01HL137927, R01HL148667 and R01HL147148 (XZ).


Assuntos
Células Epiteliais Alveolares/metabolismo , Autorrenovação Celular , Proteínas Ativadoras de GTPase/metabolismo , Enfisema Pulmonar/metabolismo , Células-Tronco/metabolismo , Via de Sinalização Wnt , Células Epiteliais Alveolares/citologia , Animais , Feminino , Proteínas Ativadoras de GTPase/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Enfisema Pulmonar/etiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Poluição por Fumaça de Tabaco/efeitos adversos
20.
J Agric Food Chem ; 69(29): 8065-8080, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34269568

RESUMO

Sodium salt is a pivotal ingredient in traditional fermented foods, but its excessive consumption adversely affects human health, product quality, and production efficiency. Therefore, reducing sodium salt content in traditional fermented foods and developing low-sodium fermented foods have attracted increasing attention. Given the essential role of sodium salt in the safety and quality of fermented foods, appropriate approaches should be applied in the production of low-sodium fermented foods. In this review, the challenges of sodium reduction in traditional fermented foods are presented, including the possible growth of pathogenic bacteria, the formation of hazardous chemicals, flavor deficiency, and texture deterioration. Physical, chemical, and biological strategies are also discussed. This review provides references for improving the quality and safety of low-sodium fermented foods.


Assuntos
Alimentos e Bebidas Fermentados , Bactérias , Fermentação , Humanos , Sódio , Paladar
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