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1.
ACS Sens ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36384296

RESUMO

As a common toxic gas, nitrogen dioxide (NO2) seriously threatens the environment and human respiratory system even at part per billion (ppb) level. Covalent organic frameworks (COFs) have gained widespread attention in sensing applications because of the benefits of designability, environmental stability, and a large number of active sites. However, the competitive adsorption of water molecules and the target gas molecules at room temperature as well as the weak interaction between COFs and gas molecules hinder their practical applications. Here, we introduce ion-in-conjugation (IIC) into a covalent organic framework (COF) by preparing a condensate of squaraine (SA) with 1,3,5-tris(4-aminophenyl)benzene (TAPB) to form a mesoporous macrocyclic material (SA-TAPB). Layers of SA-TAPB, drop cast onto interdigitated Ag-Pd alloy electrodes, show a statistically significant conductivity response to NO2 at concentrations as low as 30 ppb and a theoretical detection limit of 10.9 ppb. The sensor displays a lower sensitivity to variations in humidity when operated at 80 °C compared to room temperature. The density functional theory (DFT) calculations indicated that the main adsorption site of NO2 is dual hydrogen bonds formed between two amide hydrogen atoms of SA-TAPB and the NO2 molecule. Gas adsorption experiments revealed that SA-TAPB has the largest adsorption capacity of NO2 versus other interference gases, which were responsible for the excellent selectivity toward NO2.

2.
Open Forum Infect Dis ; 9(10): ofac512, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36324321

RESUMO

Background: Previous studies have shown gender differences in tuberculosis (TB) incidence; however, gender disparity has not been well documented across granular categorizations of anatomic sites affected by TB and in the presence of human immunodeficiency virus (HIV) coinfection, largely due to small sample size for less common TB clinical presentations and lack of detailed clinical data. Methods: The study population included TB cases aged ≥15 years (n = 41, 266) diagnosed in Harare, Zimbabwe. This cross-sectional study estimated male-to-female ratio (M/F ratio) for (1) age-specific TB incidence, (2) age-specific HIV prevalence among incident TB cases, and (3) 9 types of TB defined by affected anatomic site. Results: Males were at a 53% higher risk of TB compared to females (risk ratio [RR] = 1.53; 95% confidence interval [CI], 1.12-2.09). Based on adjusted odds ratios (aORs) from multinomial logistic regression model, the odds of abdominal TB (aOR = 0.51; 95% CI, .39-.68), TB bones/joints/spine (aOR = 0.63; 95% CI, .45-.90), and "other" extrapulmonary TB sites (aOR = 0.69; 95% CI = .59-.81) versus pulmonary TB were lower among males compared to females. The risk of TB-HIV coinfection among males was 17% (RR = .83; 95% CI, .74-.93) and 8% (RR = 0.92; 95% CI, .88-.95) lower in the 15- to 24-year and 25- to 44-year age groups, respectively. Conclusions: This study revealed a nuanced role of gender across finer categorizations of TB, indicating the need for future research to delineate underlying mechanisms driving gender disparities in TB. The finding that women had a greater likelihood of severe forms of TB and TB-HIV coinfection compared to men has important implications for women's health in TB-HIV high-burden settings.

3.
World J Clin Cases ; 10(28): 10339-10345, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36246839

RESUMO

BACKGROUND: Chronic myeloid leukemia (CML) is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid phenotype. Some patients with CML can also progress to blast crisis phase; however, the transformation of CML into Philadelphia-positive lymphoma is extremely rare. CASE SUMMARY: We present a patient with CML who experienced a sudden transformation to anaplastic large-cell lymphoma (ALCL) after 7 mo of treatment with imatinib, during which she had achieved partial cytogenetic response as well as early molecular response. The patient noticed a mass in her left shoulder, the biopsy data of which were consistent with ALCL; moreover, her lymphoma cells exhibited BCR-ABL gene fusion. The patient was diagnosed with Philadelphia-positive ALCL that progressed from CML, and was thus treated with the second generation tyrosine kinase inhibitor nilotinib. Six months later, the mass had totally disappeared and the BCR-ABL fusion gene was undetectable in the peripheral blood. To our knowledge, this is the first patient known to have developed Philadelphia-positive ALCL transformed from CML. CONCLUSION: Unexplained lymphadenopathy or an extramedullary mass in a patient with CML may warrant a biopsy and testing for BCR-ABL fusion.

4.
Molecules ; 27(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36234715

RESUMO

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.


Assuntos
Alcaloides , Alcaloides de Berberina , Produtos Biológicos , Medicamentos de Ervas Chinesas , Alcaloides/química , Benzimidazóis/análise , Alcaloides de Berberina/análise , Produtos Biológicos/química , Cromatografia Líquida de Alta Pressão/métodos , Misturas Complexas , Medicamentos de Ervas Chinesas/química , Rizoma/química , Enxofre/análise
5.
J Diabetes Complications ; 36(11): 108317, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36215794

RESUMO

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and 'multiomics' arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/diagnóstico , Pé Diabético/epidemiologia , Pé Diabético/terapia , Amputação , Salvamento de Membro , Cicatrização , Biomarcadores
6.
Zhen Ci Yan Jiu ; 47(10): 891-5, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36301166

RESUMO

OBJECTIVE: To observe the effect of acupuncture at "Sanyinjiao" (SP6) on sperm motility, testicular B cell lymphoma/leukelia-2 (Bcl-2), Bcl-2 associated X protein (Bax), and Caspase-3 in mice with oligoasthenospermia induced by microwave radiation, so as to explore its underlying mechanisms in improving oligoasthenospermia. METHODS: Male BALB/C mice were randomly divided into control, model and acupuncture groups(n=6 in each group). The oligoasthenospermia model was established by continuous microwave irradiation with frequency of 2 450 MHz and power density of 40 mW/cm2, 1 h daily for 18 days. At the same time, manual acupuncture was applied to the acupuncture group on bilateral "Sanyinjiao" (SP6) for 30 s, once daily for 18 days. Sperm motility including the percentages of progressive motility (PR), non-progressive motility (NP), and PR + NP sperms was detected by computer-assisted sperm analysis, H.E. staining was used to observe the testicular morphology and Johnson score was calculated, the expression levels of Bcl-2, Bax and Caspase-3 in testis were detected by immunofluorescence. RESULTS: Compared with the control group, the percentages of PR sperms, NP sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly decreased (P<0.05), while the expression levels of Bax and Caspase-3 were increased (P<0.05) in the model group. Compared with the model group, the percentages of PR sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly increased (P<0.05), while the expression levels of Bax and Caspase-3 were decreased (P<0.05) in the acupuncture group. Outcomes of H.E. staining showed that the seminiferous tubules became thinner, spermatogenic cells and sperm decreased or even disappeared, and the supporting cells were partially missing in the model group, which was relatively milder in the acupuncture group. CONCLUSION: Manual acupuncture at SP6 can improve sperm motility in oligoasthenospermia mice induced by microwave radiation, which may be related to its effects in down-regulating the expressions of Bax and Caspase-3, increasing expression of Bcl-2 in the testis.


Assuntos
Terapia por Acupuntura , Micro-Ondas , Animais , Masculino , Camundongos , Apoptose , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sêmen/metabolismo , Motilidade Espermática
7.
Oncol Lett ; 24(4): 356, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36168315

RESUMO

The evolutionary properties of organisms lead to the issue of targeted drug resistance. Numerous clinical trials have shown that tumor-associated macrophages (TAMs) in patients with lung cancer adversely affect the clinical efficacy of epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanism by which TAMs influence the tumor cell response to TKIs remains unclear. The aim of the present study was to investigate the influence of TAM-derived exosomes on the sensitivity of PC9 and HCC827 lung adenocarcinoma cells to the EGFR inhibitor gefitinib. Multiple cytokines were used to induce the differentiation of THP-1 human leukemia monocytes into macrophages in vitro. The obtained cells were identified as TAMs by cytomorphology and flow cytometry. Exosomes were extracted from the TAM culture supernatants and identified using electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to examine the apoptosis of lung adenocarcinoma cells when treated with gefitinib and/or TAM-derived exosomes. In addition, western blotting was used to detect the expression of the key proteins of the AKT, ERK1/2 and STAT3 signaling pathways. TAM-derived exosomes were successfully obtained. The TAM-derived exosomes were shown to affect the proliferation and apoptosis of lung adenocarcinoma cells. Furthermore, the killing effect of gefitinib on the tumor cells was attenuated. The mechanism underlying the effects of the TAM-derived exosomes may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. In conclusion, the findings indicate that TAM-derived exosomes promote resistance to gefitinib in non-small cell lung cancer (NSCLC), and the mechanism may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. This study may serve as a reference in the exploration of alternative strategies for NSCLC following the development of resistance to EGFR-targeted drugs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36173318

RESUMO

OBJECTIVES: Establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical, and progressive ILD was provided to eighty-three experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least 4 experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥ 75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%), and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT (HRCT)); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression, and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

9.
Cancer Gene Ther ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36076064

RESUMO

The abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is an important precipitating factor for the inception and development of colorectal cancer (CRC), one of the most common tumors worldwide. As a pro-apoptotic transcription factor, monocyte chemotactic protein-induced protein 1 (MCPIP1) has been closely associated with many tumor types. In the present study, the expression of MCPIP1 was firstly discovered reduced in CRC tissues and correlated with poor patient prognosis. The decreased expression was caused by promoter hypermethylation. Overexpressed MCPIP1 was found to inhibit the proliferative and migratory abilities of CRC cells, whereas knockdown of MCPIP1 produced the opposite result. The subsequent investigation demonstrated that MCPIP1 exerted its "anti-cancer" effect by suppression of the NF-κB signaling pathway through negative regulation of K63-linked ubiquitylation of TNF receptor associated factor 6 (TRAF6). Therefore, our results indicate a prognostic marker for CRC and a theoretical basis for MCPIP1 as a treatment.

10.
N Engl J Med ; 387(13): 1173-1184, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36066078

RESUMO

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antibacterianos/uso terapêutico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Glucocorticoides/uso terapêutico , Glicopirrolato , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Tabaco/efeitos adversos , Resultado do Tratamento
11.
World Neurosurg ; 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36064116

RESUMO

BACKGROUND: Despite the arousal effect of median nerve stimulation (MNS) being well documented in the clinical treatment of coma patients with traumatic brain injury (TBI), the mechanisms underlying the observed effect are still not completely understood. This study aimed to evaluate the protective effects and potential mechanism of MNS in comatose rats with TBI. METHODS: A total of 60 rats were randomly divided into 5 groups: the control group, sham-stimulated group, MNS group, orexins receptor type 1 (OX1R) antagonist group, and antagonist control group. The free-fall drop method was used to establish a TBI model. After administrating MNS or OX1R antagonist, consciousness was evaluated. Protein levels in the prefrontal cortex were measured using an enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence. RESULTS: In the MNS group, tissue damage and consciousness state was markedly improved compared with that in the sham-stimulated group. Administration of the OX1R antagonist attenuated the beneficial effects of MNS in TBI-induced comatose rats. Additionally, MNS also significantly enhanced the expression of orexin-A/OX1R and the activation of Ras guanine nucleotide-releasing factor 1 (RasGRF1). CONCLUSIONS: These data show that MNS exerts its wake-promoting effect by activating the OX1R-RasGRF1 pathway in TBI-induced comatose rats.

12.
Huan Jing Ke Xue ; 43(9): 4791-4799, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096619

RESUMO

In order to study the distribution characteristics and potential risk of antimony (Sb) in urban soil, the concentrations of soil Sb in four different land use types were analyzed based on the data of 1670 soil samples with different vertical profiles in 102 plots in Shanghai. The risks were evaluated using the potential ecological risk index method and health risk assessment model. The results showed that the average ω(Sb) in the study area was 0.52 mg·kg-1, and the content of soil Sb gradually declined with the rise in soil profile depth. Sb was enriched in surface soil, which indicated that human activities had caused disturbance to the distribution of Sb in the soil. The content of Sb in the surface soil of industrial land was higher than that of residential land and commercial land, and the content of Sb in agricultural land was the lowest. The single-factor pollution index of industrial land was the highest, reaching a slight pollution level, whereas the residential land, commercial land, and agricultural land were at even-clean or clean levels, respectively. The whole region showed slight ecological risk, with the potential ecological risk index ranging from 4.23 to 7.61. The potential ecological risk level of industrial land was moderate, which needs to be addressed. The results of health risk assessment showed that the non-carcinogenic risk of Sb in the soil was low; however, it is of great concern to residents, especially children, when on residential land.


Assuntos
Metais Pesados , Poluentes do Solo , Antimônio , Criança , China , Monitoramento Ambiental/métodos , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
13.
Anal Chim Acta ; 1226: 340268, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36068064

RESUMO

The cellular metabolism of metals is highly critical to elucidate their potential cytotoxicity or cell protection mechanism. In this work, an asymmetric serpentine microfluidic device (ASMD) with high sampling efficiency and excellent focusing performance was developed for single-cell focusing. ASMD coupling with ICP-MS ensures single-cell assay to provide the information for trivalent arsenic (As(III)) uptake by HepG2 cells, which reveals the heterogeneity of cellular arsenic distribution, and elucidates the arsenic elimination behaviors in single HepG2 cells. Further, the metabolism and transformation of As(III) in HepG2 cells was tracked by hyphenating capillary electrophoresis (CE) separation with ICP-MS. The results for single-cell analysis and arsenic elimination kinetics illustrated that the half-life of arsenic elimination is 0.9 ± 0.04 h with the elimination constant of 0.77 ± 0.03, i.e., 77% of accumulated As in HepG2 cells may be eliminated per hour. Moreover, arsenobetaine (AsB) was identified to be the main metabolite and biotransformation species of As in HepG2 cells. ASMD-ICP-MS and CE-ICP-MS are powerful for tracking the fate of metals or metal drugs in single cells to comprehensively understand their metabolic pathway and transformation behaviors.


Assuntos
Arsênio , Arsênio/análise , Arsênio/toxicidade , Eletroforese Capilar/métodos , Células Hep G2 , Humanos , Espectrometria de Massas/métodos , Análise Espectral
14.
Lancet Microbe ; 3(11): e824-e834, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36115379

RESUMO

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H3N8 , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Humanos , Animais , Pré-Escolar , Influenza Aviária/epidemiologia , Vírus da Influenza A Subtipo H3N8/genética , Influenza Humana/epidemiologia , Filogenia , Estudos Retrospectivos , Galinhas , Aves Domésticas , Patos , Mamíferos
15.
Plant J ; 112(3): 630-645, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36071028

RESUMO

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication event prior to the W. villosa-Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.


Assuntos
Alquil e Aril Transferases , Alquil e Aril Transferases/genética , Terpenos/metabolismo , Plantas/metabolismo , Cromossomos
16.
Int J Biol Macromol ; 222(Pt A): 429-437, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126812

RESUMO

We prepared a series of highly porous Polyrotaxane/sodium alginate, and Polyrotaxane/Chitosan foam alloys according to a sustainable pathway by using water as the only solvent. The foam alloys were further used as supporter materials for poly (ethylene glycol) (PEG) encapsulation, to fabricate shape-stable bio-based phase change materials (PCMs). The pore morphology and the internal interface between PEG and foam alloys were characterized by scanning electron microscope (SEM). Due to the good compatibility between foam alloys and PEG, the PCM performed perfect anti-leakage properties. The introduction of sodium alginate or Chitosan ensures the shape stability of the PCMs during the phase transition. The PCMs performed good cycle stability and showed ultra-high latent heat (171.6 J g-1-189.5 J g-1). Finally, we compared the typical indicators of this work with those reported in the literature, and the comparison highlighted that the present PCMs have the significant advantages: high melting enthalpy, convenient preparation and outstanding sustainability. Notably, the work provided a sustainable idea for the design of anti-leakage and shape-stable PEG-based PCMs.


Assuntos
Quitosana , Rotaxanos , Alginatos , Temperatura Alta , Polietilenoglicóis , Ligas
17.
Hepatology ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069569

RESUMO

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin (p = 0.04) and IL-8 (p < 0.001) and MMP-7 (p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2  = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated (p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 (p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

18.
J Pediatr Gastroenterol Nutr ; 75(5): 635-642, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36070552

RESUMO

OBJECTIVES: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. METHODS: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. RESULTS: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. CONCLUSIONS: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.


Assuntos
Fibrose Cística , Hepatopatias , Humanos , Pré-Escolar , Qualidade de Vida , Estudos Prospectivos , Nível de Saúde , Fibrose Cística/complicações , Fibrose Cística/diagnóstico por imagem , Inquéritos e Questionários , Hepatopatias/etiologia , Hepatopatias/complicações
19.
J Agric Food Chem ; 70(38): 11944-11957, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36120893

RESUMO

Dietary saponins have the potential to ameliorate atherosclerosis (AS). Gypenosides of Gynostemma pentaphyllum (GPs) have been used as functional foods to exhibit antiatherosclerotic activity. The present study aimed to explore the protective effect, underlying mechanism and active substances of GPs on AS in vivo and in vitro. Results demonstrated GPs administration reduced the serum concentrations of TC and LDL-C, upregulated the plasma HDL-C content, inhibited the secretion of ICAM-1, VCAM-1, and MCP-1, and alleviated vascular lesions in VitD3 plus high cholesterol diet-induced AS rats as well as reduced adhesion factors levels in ox-LDL-stimulated HUVECs, which was potentially associated with suppressing PCSK9/LOX-1 pathway. Further activity-guided phytochemical investigation of GPs led to the identification of five new dammarane-type glycosides (1-5) and ten known analogs (6-15). Bioassay evaluation showed compounds 1, 6, 7, 12, 13, and 14 observably reduced the expressions of PCSK9 and LOX-1, as well as the secretion of adhesion factors in injured HUVECs. Molecular docking experiments suggested that the active saponins of GPs might bind to the allosteric pocket of PCSK9 located at the catalytic and C-terminal domains, and 2α-OH-protopanaxadiol-type gypenosides might exert a higher affinity for an allosteric binding site on PCSK9 by hydrogen-bond interaction with ARG-458. These findings provide new insights into the potential nutraceutical application of GPs and their bioactive compounds in the prevention and discovery of novel therapeutic strategies for AS.


Assuntos
Aterosclerose , Saponinas , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , LDL-Colesterol , Gynostemma/química , Hidrogênio , Molécula 1 de Adesão Intercelular , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pró-Proteína Convertase 9 , Ratos , Saponinas/química , Receptores Depuradores Classe E , Molécula 1 de Adesão de Célula Vascular
20.
Aging (Albany NY) ; 14(18): 7455-7469, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36126193

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a serious hazard to human health and is characterized by high rates of disability and mortality. It is necessary to explore new effective treatment methods to reduce the impact of TBI on individuals and society. As an emerging neuromodulation technique, ultrasound is used to treat some neurological diseases, but the neuroprotective mechanism of low-intensity focused ultrasound (LIFUS) in TBI remains unclear. We aimed to investigate the protective effects and potential mechanisms of LIFUS in TBI. METHODS: A rat model of TBI was established using the free-fall method. After establishing the TBI model, the hypothalamus region was covered with LIFUS radiation, and an orexin receptor 1 (OXR1) antagonist (SB334867) was injected intraperitoneally. Neurobehavioral examination, Nissl staining, hematoxylin and eosin staining of the brain tissue, and brain water content, were performed 3 days later. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence staining, and immunohistochemical staining, were used to evaluate the neuroprotective mechanisms of LIFUS. RESULTS: LIFUS improved tissue damage, neurological deficits, and brain edema. LIFUS can increase the expression of orexin-A (OX-A) and OXR1, significantly inhibit the activation of nuclear factor-κB (NF-κB) protein and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome after TBI, and reduce the release of pro-inflammatory factors after TBI; however, SB334867 can reverse this effect. CONCLUSIONS: This study suggests that LIFUS may play a neuroprotective role by promoting the release of OX-A from the hypothalamus and inhibiting the inflammatory response after TBI through the OX-A /NF-κB/NLRP3 pathway.


Assuntos
Lesões Encefálicas Traumáticas , NF-kappa B , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/terapia , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Humanos , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nucleotídeos , Receptores de Orexina , Orexinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Água
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