Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.457
Filtrar
1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268499

RESUMO

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35014246

RESUMO

Developing energy-efficient alternatives for methane (CH4) purification from natural gas and methane capture of coal-mine gas is of great significance and challenge in the chemical industry. Herein, we report a robust nickel-based metal-organic framework (MOF), Ni-BPZ, featuring one-dimensional (1D) rhombic channels decorated with abundant pyrazole rings. Ni-BPZ exhibits excellent separation performance toward both C2H6/CH4 and CH4/N2 binary mixtures. The C2H6/CH4 selectivity of Ni-BPZ is high, up to 50.2, exceeding those of most MOF adsorbents reported, and it simultaneously possesses a remarkable C2H6 uptake of 2.46 mmol/g at 298 K and 0.1 bar. The CH4/N2 selectivity of Ni-BPZ reaches 6.6, and its high CH4 uptake is 1.56 mmol/g, which is also superior to most high-performance CH4 adsorbents. The molecular simulation reveals that the uniform 1D rhombic channels with abundant pyrazole rings provide a high density of potential adsorption sites for efficient C2H6/CH4 and CH4/N2 separations.

3.
Brief Bioinform ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35018405

RESUMO

Since miRNAs can participate in the posttranscriptional regulation of gene expression, they may provide ideas for the development of new drugs or become new biomarkers for drug targets or disease diagnosis. In this work, we propose an miRNA-disease association prediction method based on meta-paths (MDPBMP). First, an miRNA-disease-gene heterogeneous information network was constructed, and seven symmetrical meta-paths were defined according to different semantics. After constructing the initial feature vector for the node, the vector information carried by all nodes on the meta-path instance is extracted and aggregated to update the feature vector of the starting node. Then, the vector information obtained by the nodes on different meta-paths is aggregated. Finally, miRNA and disease embedding feature vectors are used to calculate their associated scores. Compared with the other methods, MDPBMP obtained the highest AUC value of 0.9214. Among the top 50 predicted miRNAs for lung neoplasms, esophageal neoplasms, colon neoplasms and breast neoplasms, 49, 48, 49 and 50 have been verified. Furthermore, for breast neoplasms, we deleted all the known associations between breast neoplasms and miRNAs from the training set. These results also show that for new diseases without known related miRNA information, our model can predict their potential miRNAs. Code and data are available at https://github.com/LiangYu-Xidian/MDPBMP.

4.
Lancet Reg Health West Pac ; 20: 100361, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35036977

RESUMO

Background: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. Findings: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. Interpretation: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. Funding: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

6.
Materials (Basel) ; 15(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35057303

RESUMO

To study the influence of nano-additives on the friction-wear characteristics of friction materials, the nano-sized silicon carbide particles which have excellent chemical and physical properties are considered to add in composite to form the modified friction material. The influence of the silicon carbide nanoparticles (SCN) on the friction-wear characteristics of copper-based friction materials (CBFM) is investigated via the SAE#2 (made in Hangzhou, China) clutch bench test with the applied pressure, rotating speed, and automatic transmission fluid (ATF) temperature taken into account. Moreover, the variations of friction torque and temperature are considered to evaluate the friction performance, and the variable coefficient is employed to describe the friction stability. The wear characteristics of friction materials are investigated by the disc changes in thickness and micro-morphology. The results show that the CBFM with SCN can provide a higher friction torque, which increased by 30% to 50% compared with CBFM. The variable coefficient of CBFM with SCN changes from 674 to 52 with the rotating speed raised from 600 rpm to 3000 rpm, which shows that the friction stability is relatively worse. Furthermore, the micromorphology shows that the CBFM with SCN has lower porosity and surface roughness, which increases the microscopic contact area and the coefficient of friction (COF). Simultaneously, the reduction in porosity also leads to a decrease in the cooling quality, bringing about a rapid temperature rise. Thus, the wear amount of CBFM with SCN increases significantly, especially for the friction disc in the axial middle position.

7.
Int Immunopharmacol ; 103: 108467, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34933161

RESUMO

Growing evidence indicates that synovial hypoxia-inducible factor 1α (HIF-1α) can be as a promising target for RA therapy. We previously reported that AMSP-30 m as a novel HIF-1α inhibitor had potent activities of anticancer metastasis. This study clarified the therapeutic effects of HIF-1α inhibitor AMSP-30 m on adjuvant-induced arthritis (AIA) in rats and explored the possible mechanisms. AMSP-30 m was given intraperitoneally to AIA rats, and its therapeutic effects and anti-inflammatory activity were evaluated. The influences of AMSP-30 m on synovial apoptosis, angiogenesis and sonic hedgehog (Shh) pathway were examined. We found that, accompanied with the inhibition of synovial HIF-1α expression, AMSP-30 m had potent anti-arthritic and anti-inflammatory effects on AIA rats, evidenced by the reduction in paw swelling, arthritis index, histopathological scores, and the production of IL-1ß, IL-6, TNF-α in serum and synovial tissues. AMSP-30 m reduced synovial Ki67 expression and increased TUNEL-positive index, indicating its anti-proliferative and pro-apoptotic effects on AIA synovial cells, which was related to reducing Bcl-2 protein level and increasing Bax, cleaved caspase 3 protein levels. Additionally, AMSP-30 m showed anti-angiogenic effects within AIA synovium, indicated by the reduction of synovial VEGF expression and blood vessels number (especially CD31+/αSMA- immature vessels, but not CD31+/αSMA+ mature vessels). Moreover, AMSP-30 m inhibited the activation of synovial Shh pathway, suggested by the reduction of pathway-related proteins, like Shh, Smo, Gli-1, cyclin D1 and c-Myc. Collectively, HIF-1α inhibitor AMSP-30 m exerted potent anti-arthritic effects on AIA rats possibly by promoting synovial apoptosis, reducing synovial angiogenesis and inhibiting Shh pathway.

8.
Langmuir ; 38(2): 801-809, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34951309

RESUMO

Surface-enhanced Raman scattering (SERS) has been a useful sensing technique, in which inelastic light scattering can be significantly enhanced by absorbing molecules onto rough metal surfaces or nanoparticles. Although many methods have been developed to prepare SERS substrates, it is still highly desirable and challenging to design SERS substrates, especially with highly ordered and controlled three-dimensional (3D) structures. In this work, we develop novel SERS substrates with regular volcano-shaped polymer structures using the versatile solvent on-film annealing method. Polystyrene (PS) nanospheres are first synthesized by surfactant-free emulsion polymerization and assembled on poly(methyl methacrylate) (PMMA) films. After annealing in acetic acid vapors, PMMA chains are selectively swollen and wet the surfaces of the PS nanospheres. By selectively removing the PS nanospheres using cyclohexane, volcano-shaped PMMA films can be obtained. Compared with flat PMMA films with water contact angles of ∼74°, volcano-shaped PMMA films exhibit higher water contact angles of ∼110° due to the sharp features and rough surfaces. The volcano-shaped PMMA films are then coated with gold nanoparticles (AuNPs) as SERS substrates. Using rhodamine 6G as the probe molecules, the SERS results show that the Raman signals of the volcano-shaped PMMA/AuNP hybrid substrates are much higher than those of the pristine PMMA films and PMMA films with AuNPs. For the volcano-shaped PMMA/AuNP hybrid substrates using 400 nm PS nanospheres, a high enhancement factor (EF) value of ∼1.12 × 105 with a detection limit of 10-8 M is obtained in a short integration time of 1 s. A linear calibration line with an R2 value of 0.918 is also established, demonstrating the ability to determine the concentrations of the analytes. This work offers significant insight into developing novel SERS substrates, which is crucial for improving the detection limits of analytes.

9.
Environ Pollut ; 296: 118748, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34958848

RESUMO

The bioaccumulation and biomagnification of perfluoroalkyl acids (PFAAs) in temperate urban lacustrine ecosystems is poorly understood. We investigated the occurrence and trophic transfer of and probabilistic health risk from 15 PFAAs in the food web of Luoma Lake, a temperate urban lake in East China. The target PFAAs were widely distributed in the water (∑PFAA: 77.09 ± 9.07 ng/L), suspended particulate matter (SPM) (∑PFAA: 284.07 ± 118.05 ng/g dw), and sediment samples (∑PFAA: 67.77 ± 17.96 ng/g dw) and occurred in all biotic samples (∑PFAA: 443.27 ± 124.89 ng/g dw for aquatic plants; 294.99 ± 90.82 for aquatic animals). PFBA was predominant in water and SPM, with 40.11% and 21.35% of the total PFAAs, respectively, while PFOS was the most abundant in sediments (14.11% of the total PFAAs) and organisms (14.33% of the total PFAAs). Sediment exposure may be the major route of biological uptake of PFAAs. The PFAA accumulation capacity was the highest in submerged plants, followed by emergent plants > bivalves > crustaceans > fish > floating plants. Long-chain PFAAs were biomagnified, and short-chain PFAAs were biodiluted across the entire lacustrine food web. PFOS exhibited the greatest bioaccumulation and biomagnification potential among the target PFAAs. However, biomagnification of short-chain PFAAs was also observed within the low trophic-level part of the food web. Human health risk assessment indicated that perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) posed health risks to all age groups, while the other PFAAs were unlikely to cause immediate harm to consumers in the region. This study fills a gap in the knowledge of the transfer of PFAAs in the food webs of temperate urban lakes.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/análise , Animais , Bioacumulação , China , Ecossistema , Monitoramento Ambiental , Fluorcarbonetos/análise , Cadeia Alimentar , Humanos , Lagos , Poluentes Químicos da Água/análise
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120254, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34384993

RESUMO

Spectral unmixing algorithm is one of the key technologies for spectral flow cytometer in biology, chemistry and medicine. The proposed algorithm can separate the overlapping spectra automatically without the premeasured single stained or un-stained samples as the basic pure spectra. Genetic algorithm is adopted to search the optimal positions and peak sharps of the basic spectra derived from the unknown components, and then the concentration of each component can be estimated simultaneously by least squares method. Compared with conventional methods, the proposed algorithm has a wider application scope, such as the multi-stained samples with unknown components or the samples with auto-fluorescence. In the simulation, the convergence rate, accuracy and stability of the proposed algorithm are evaluated under the conditions of completely and partly unknown components. In the experiment, the flow spectra of cyanobacteria are processed, and the results demonstrate the feasibility and effectiveness of the proposed algorithm.


Assuntos
Algoritmos , Corantes Fluorescentes , Citometria de Fluxo , Análise dos Mínimos Quadrados
11.
Chemosphere ; 288(Pt 1): 132509, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34627811

RESUMO

Herein, polypyrrole/titanium oxide/reduced graphene oxide (PTi/r-GO) electrodes were prepared and successfully applied for the photoelectrocatalytic (PEC) degradation of methyl orange (MO) under visible light. Polypyrrole-TiO2 composites rich in p-n heterojunctions were first prepared, then modified with r-GO to improve the electrical conductivity and facilitate charge separation under visible light irradiation. The obtained PTi/r-GO composites were then deposited onto a titanium mesh, which served as the working electrode in PEC experiments. A MO removal efficiency of 93% was achieved in 50 min using PTi/r-GO electrode under PEC conditions (Xe lamp, λ > 420 nm, bias of 0.6 V, 0.1 M Na2SO4 electrolyte), which was far higher than MO removal efficiencies under electrocatalytic oxidation (22%) or photocatalytic oxidation (47%) conditions. This confirmed that excellent activity of the PTi/r-GO electrode under PEC conditions was due to a combination of electrochemical and photocatalytic oxidation processes (involving •OH and •O2- generation). Further, PTi/r-GO was very stable under the applied PEC conditions, with the MO removal efficiency remaining >90% after five cycles. PEC degradation pathways for MO on PTi/r-GO were explored, with a number of key intermediates in the MO mineralization process identified. Results demonstrate that PEC electrodes combining p-type polypyrrole, n-type TiO2 and rGO are very effective in the treatment of hazardous organic compounds in wastewater.


Assuntos
Polímeros , Titânio , Catálise , Corantes , Eletrodos , Grafite , Luz , Pirróis
12.
Microbiol Res ; 254: 126912, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34742105

RESUMO

Sapindus saponins extracted from Sapindus mukorossi Gaertn. have been reported to exert antibacterial activity against Cutibacterium acnes (C. acnes). However, there are no reports about their potentials against its biofilm, which is a major contributor to the antibiotic resistance of C. acnes. This study aimed to investigate the synergistic antibiofilm activity and action of the combination of Sapindoside A and B (SAB) against C. acnes. SAB with sub-MICs significantly inhibited the early-formed and mature biofilm of C. acnes and decreased the adhesion and cell surface hydrophobicity (p < 0.05). Also, SAB greatly reduced the production of exopolysaccharide and lipase (p < 0.05), and the binding mode of SAB and lipase was predicted by molecular docking, via hydrogen bonds and hydrophobic interactions. Biofilm observed with electron microscopies further confirmed the high antibiofilm activity of SAB against C. acnes. Furthermore, a significant down-regulation of biofilm biosynthesis-associated genes was observed. The combination index explained the synergistic effects of SAB leading to the above results, and the contribution of SA was greater than that of SB. The current results showed that SAB had synergistic antibiofilm activity against C. acnes, and the Sapindoside A played a major role, indicating that SAB could be a natural antiacne additive against C. acnes biofilm-associated infections.


Assuntos
Biofilmes , Ácido Oleanólico/análogos & derivados , Propionibacteriaceae , Saponinas , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Simulação de Acoplamento Molecular , Ácido Oleanólico/farmacologia , Propionibacteriaceae/efeitos dos fármacos , Saponinas/farmacologia
13.
Eur J Cancer Prev ; 31(1): 7-13, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871197

RESUMO

FCGR2A, ORAI1 and CD40 are all involved in the immune and inflammatory responses in the human body, whereas its association with lung cancer is still unclear. This study aimed to investigate the effects of polymorphisms in these genes on the susceptibility to lung cancer. Six candidate single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a discovery cohort, including 400 lung cancer patients and 400 healthy controls, and validated in a replication cohort, including 529 lung cancer cases and 532 controls. Comparing the allele frequency distributions, we found that the rs1801274-G, rs511278-T and rs1883832-T were risk alleles for lung cancer (P < 0.05), whereas the minor allele of rs12320939-T was a protective allele for the disease (P = 0.037). Comparing the genotype frequency distributions, we found that rs1801274-GG, rs511278-CT and of rs1883832-TT were risk genotype for lung cancer (P < 0.05). Genetic model analysis showed that the rs1801274 A>G was correlated with an elevated risk of lung cancer in recessive and log-additive models (P < 0.05); rs511278 C>T exhibited an increased risk of disease in dominant and log-additive models (P < 0.05); rs1883832 C>T had a strong relationship with risk of disease in all three models (P < 0.001), whereas rs12320939 G>T was correlated to a reduced risk of disease in recessive and log-additive models (P < 0.05). Finally, the association between the above SNPs and lung cancer risk was validated in a replication cohort (P < 0.05). These results shed new light on the association between immune-related genes and risk of lung cancer, and might be useful for the identification of high-risk individuals.

14.
Chemosphere ; 287(Pt 1): 132064, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34474389

RESUMO

The occurrence, spatial distribution, potential sources, and risk assessment of 14 perfluoroalkyl acids (PFAAs), including 11 perfluoroalkyl carboxylic acids and 3 perfluoroalkyl sulfonates acids, were investigated in 21 drinking water sources from the lower Yangtze River in November 2019. The total PFAAs (∑PFAAs) concentrations ranged from 39.3 to 220.3 ng/L, and perfluorooctanoic acid and perfluorooctanesulfonate were predominant with average concentrations of 19.4 and 15.4 ng/L, respectively. The higher ∑PFAAs concentrations in the southern shore and downstream could be attributed to industrial development and surface runoff/tide currents, respectively. Principal component analysis-multiple linear regression revealed that the primary sources of PFAAs were fluororesin coatings/metal plating, surface runoff/textile, effluent discharge/food packaging, and leather/fabrics. Human intake risks of PFAAs were assessed by target hazard quotient (THQ), which showed that human health risks of PFAAs decreased with increasing age, excluding 13-17 years age group. Moreover, the total exposure risks of PFOA/PFOS in all sampling sites to people aged over 18 years calculated based on contribution from drinking water were noted to be at safe level. The results obtained were helpful for improving our understanding of human health risks of PFAAs, and expanding our knowledge on PFAAs in drinking water.


Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorcarbonetos , Poluentes Químicos da Água , Adolescente , Adulto , Ácidos Alcanossulfônicos/análise , Caprilatos/análise , China , Monitoramento Ambiental , Fluorcarbonetos/análise , Humanos , Pessoa de Meia-Idade , Medição de Risco , Poluentes Químicos da Água/análise
15.
Environ Microbiol ; 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863027

RESUMO

Brown root rot (BRR) caused by Phellinus noxius is a destructive tree disease in tropical and subtropical areas. To understand how BRR affects the composition of the plant rhizoplane-enriched microbiota, the microbiomes within five root-associated compartments (i.e., bulk soil, old/young root rhizosphere soil, old/young root tissue) of Ficus trees naturally infected by P. noxius were investigated. The level of P. noxius infection was determined by quantitative PCR. Illumina sequencing of the internal transcribed spacer and 16S rRNA revealed that P. noxius infection caused a significant reduction in fungal diversity in the bulk soil, old root tissue, and rhizosphere soil. Interestingly, Cosmospora was the only fungal genus positively correlated with P. noxius. The abundance and composition of dominant bacterial taxa such as Actinomadura, Bacillus, Rhodoplanes, and Streptomyces differed between BRR-diseased and healthy samples. Furthermore, 838 isolates belonging to 26 fungal and 35 bacterial genera were isolated and tested for interactions with P. noxius. Antagonistic activities were observed for isolates of Bacillus, Pseudomonas, Aspergillus, Penicillium, and Trichoderma. Cellophane overlay and cellulose/lignin utilization assays suggested that Cosmospora could tolerate the secretions of P. noxius and that the degradation of lignin by P. noxius may create suitable conditions for Cosmorpora growth. This article is protected by copyright. All rights reserved.

16.
Hematology ; 26(1): 985-994, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34871523

RESUMO

ABSTRACTObjectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM.Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment.Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly.Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy.

17.
Brief Bioinform ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850821

RESUMO

2'-O-methylation (Nm) is a post-transcriptional modification of RNA that is catalyzed by 2'-O-methyltransferase and involves replacing the H on the 2'-hydroxyl group with a methyl group. The 2'-O-methylation modification site is detected in a variety of RNA types (miRNA, tRNA, mRNA, etc.), plays an important role in biological processes and is associated with different diseases. There are few functional mechanisms developed at present, and traditional high-throughput experiments are time-consuming and expensive to explore functional mechanisms. For a deeper understanding of relevant biological mechanisms, it is necessary to develop efficient and accurate recognition tools based on machine learning. Based on this, we constructed a predictor called NmRF based on optimal mixed features and random forest classifier to identify 2'-O-methylation modification sites. The predictor can identify modification sites of multiple species at the same time. To obtain a better prediction model, a two-step strategy is adopted; that is, the optimal hybrid feature set is obtained by combining the light gradient boosting algorithm and incremental feature selection strategy. In 10-fold cross-validation, the accuracies of Homo sapiens and Saccharomyces cerevisiae were 89.069 and 93.885%, and the AUC were 0.9498 and 0.9832, respectively. The rigorous 10-fold cross-validation and independent tests confirm that the proposed method is significantly better than existing tools. A user-friendly web server is accessible at http://lab.malab.cn/∼acy/NmRF.

18.
Phys Chem Chem Phys ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854437

RESUMO

Density functional theory (DFT) calculations are carried out to investigate the effect of point defects on acetylene hydrogenation reaction over Ni(111) surface with three different defect concentrations (DC = 0.0500, 0.0625, and 0.0833), compared with the perfect Ni(111) surface. The adsorptions of C2 species and H atoms and the mechanism of acetylene hydrogenation via the ethylene pathway are systematically analyzed. The results indicate that the existence of defects will make C2 species and H atoms more inclined to adsorb near the defects. Introducing an appropriate amount of point defect concentration can enhance the catalytic activity and ethylene selectivity of Ni. In this work, DC = 0.0625 Ni(111) surface has the highest catalytic activity and selectivity of ethylene. This work provides useful theoretical information on the effect of defects on acetylene hydrogenation and is helpful for the design of Ni and related metal catalysts with defects.

19.
Oncogene ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34857889

RESUMO

The oncogenic potential of the latent transcription factor signal transducer and activator of transcription (STAT)3 in many human cancers, including lung cancer, has been largely attributed to its nuclear activity as a tyrosine-phosphorylated (pY705 site) transcription factor. By contrast, an alternate mitochondrial pool of serine phosphorylated (pS727 site) STAT3 has been shown to promote tumourigenesis by regulating metabolic processes, although this has been reported in only a restricted number of mutant RAS-addicted neoplasms. Therefore, the involvement of STAT3 serine phosphorylation in the pathogenesis of most cancer types, including mutant KRAS lung adenocarcinoma (LAC), is unknown. Here, we demonstrate that LAC is suppressed in oncogenic KrasG12D-driven mouse models engineered for pS727-STAT3 deficiency. The proliferative potential of the transformed KrasG12D lung epithelium, and mutant KRAS human LAC cells, was significantly reduced upon pS727-STAT3 deficiency. Notably, we uncover the multifaceted capacity of constitutive pS727-STAT3 to metabolically reprogramme LAC cells towards a hyper-proliferative state by regulating nuclear and mitochondrial (mt) gene transcription, the latter via the mtDNA transcription factor, TFAM. Collectively, our findings reveal an obligate requirement for the transcriptional activity of pS727-STAT3 in mutant KRAS-driven LAC with potential to guide future therapeutic targeting approaches.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1714-1718, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893099

RESUMO

OBJECTIVE: To investigate the regulation of chronic myelogenous leukemia (CML) imatinib resistant genes, in order to improve the therapeutic effect of CML imatinib resistant patients. METHODS: The human CML cell line K562 and imatinib-resistant K562 cells (K562/G01) were collected, and transcriptome of the cells were achieved by RNA-seq. The sequencing data were analyzed by using standard procedures. RESULTS: Compared with K562 cells, 464 genes were significantly changed in K562/G01 cells, including 163 up-regulated and 301 down-regulated genes. The GO function annotation analysis and KEGG pathway analysis results showed that the differentially expressed genes were mainly involved in biological processes such as oxidative phosphorylation, localization to protein organelle, ribonucleoprotein complex biogenesis and so on. Gene Set Enrichment Analysis (GSEA) plots showed that 5 gene-sets were up-regulated in K562/G01 significantly, including the pathway of TGF-beta, mTOR and CML. CONCLUSION: CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...