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1.
Endocr Relat Cancer ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38864697

RESUMO

Pheochromocytoma (PCC) and abdominal paraganglioma (aPGL) (together abbreviated PPGL) frequently present with an underlying genetic event in a PPGL driver gene, and additional susceptibility genes are anticipated. Here we re-analysed whole-exome sequencing data for PCC patients and identified two patients with rare missense variants in the calcium voltage-gated channel subunit 1H gene (CACNA1H). CACNA1H variants were also found in the clinical setting in PCC patients using targeted sequencing and from analysis of The Cancer Genome Atlas database. In total, CACNA1H variants were found in six PCC cases. Three of these were constitutional and two are known to have functional consequences on hormone production and gene expression in primary aldosteronism and aldosterone-producing adrenocortical adenoma. In general, PPGL exhibited reduced CACNA1H mRNA expression as compared to normal adrenal. Immunohistochemistry showed strong CACNA1H (CaV3.2) staining in adrenal medulla while PPGL typically had weak or negative staining. Reduced CACNA1H gene expression was especially pronounced in PCC as compared to aPGL and in PPGL with Cluster 2 kinase signalling phenotype. Furthermore, CACNA1H levels correlated with HIF1A and HIF2A. Moreover, TCGA data revealed a correlation between CACNA1H methylation density and gene expression. Expression of rCacna1h in PC12 cells induced differential protein expression profiles determined by mass spectrometry as well as a shift in the membrane potential where maximum calcium currents were observed as determined by electrophysiology. The findings suggest the involvement of CACNA1H/CaV3.2 in pheochromocytoma development and establish a potential link between the aetiology of adrenomedullary and adrenocortical tumor development.

2.
J Hazard Mater ; 475: 134866, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38870856

RESUMO

The microplastics and organic additives formed in routine use of plastic takeaway food containers may pose significant health risks. Thus, we collected plastic containers made of polystyrene, polypropylene, polyethylene terephthalate, polylactic acid and simulated two thermal usages, including hot water (I) and microwave treatments (M). Nile Red fluorescence staining was developed to improve accurate counting of microplastics with the aid of TEM and DLS analysis. The quantity of MPs released from thermal treatments was determined ranging from 285.7 thousand items/cm2 to 681.5 thousand items/cm2 in containers loaded with hot water with the following order: IPS>IPP>IPET>IPLA, while microwave treatment showed lower values ranging from 171.9 thousand items/cm2 to 301.6 thousand items/cm2. In vitro toxicity test using human intestinal epithelial Caco-2 cells indicated decrease of cell viability in raw leachate, resuspended MPs and supernatants, which might further lead to cell membrane rupture, ROS production, and decreased mitochondrial membrane potential. Moreover, the leachate inhibited the expression of key genes in the electron transport chain (ETC) process, disrupted energy metabolism. For the first time, we isolate the actually released microplastics and organic substances for in vitro toxicity testing, and demonstrate their potential impacts to human intestine. SYNOPSIS: Plastic take-out containers may release microplastics and organic substances during daily usage, both of which can cause individual and combined cytotoxic effects on human colon adenocarcinoma cells Caco-2.


Assuntos
Sobrevivência Celular , Embalagem de Alimentos , Microplásticos , Plásticos , Humanos , Microplásticos/toxicidade , Células CACO-2 , Plásticos/toxicidade , Plásticos/química , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Micro-Ondas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Temperatura Alta
3.
Food Chem X ; 22: 101459, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803669

RESUMO

Rice protein (RP) and polyphenols are often used in functional foods. This study investigated the non-covalent interactions between RP and three polyphenols (curcumin, CUR; quercetin, QUE; resveratrol, RES) and used the complexes as emulsifiers to create emulsions. Three polyphenols interacted with RP to varying extents, with QUE showing the greatest binding affinity and inducing the greatest alterations in its secondary structure. Molecular docking analysis elucidated the driving forces between them including hydrophobic interactions, hydrogen bonding, and van der Waals forces. Combination with QUE or RES induced structural changes of RP, increasing particle size of complexes. The synergistic effect of polyphenols and protein also enhanced radical scavenging capacity of complexes. Compared to pure protein, all complexes successfully created emulsions with smaller particle size (378-395 nm vs. 470 nm), higher absolute potential (37.43-38.26 mV vs. 35.62 mV), and greater lipid oxidation stability by altering protein conformation.

4.
Sci Transl Med ; 16(747): eadi2952, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748775

RESUMO

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8/9 and arginase-1 expression by MDSCs. At the same time, NK cell-derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with b2m-knockout (KO) tumor mice models. Similarly in syngeneic wild-type and IL-6 KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell-mediated mechanism that drives the development of MDSCs during tumor immune escape.


Assuntos
Tolerância Imunológica , Interleucina-6 , Células Matadoras Naturais , Células Supressoras Mieloides , Fator de Transcrição STAT3 , Fator de Transcrição STAT3/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Interleucina-6/metabolismo , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/imunologia , Animais , Humanos , Transdução de Sinais , Microambiente Tumoral/imunologia , Camundongos Knockout , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/patologia
5.
Sci Total Environ ; 937: 173348, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38795997

RESUMO

Cities usually expand on flat land. However, in recent decades, the increasing scarcity of available flat land has compelled many cities to expand to sloping land (sloping land urbanization, SLU), and the understanding for global SLU is still unclear. This study, based on the currently available high-precision global Digital Elevation Model (FABDEM) and global land cover dataset (GlobeLand30), investigated the characteristics and impacts of SLU in 26,402 urban residential areas worldwide from 2000 to 2020. Results show that the total area of SLU globally is 16,383 km2, accounting for 9.54 % of the overall urban expansion. This phenomenon is widespread globally and relatively concentrated in a few countries, with 42.78 %, 24.35 %, and 21.83 % of the area coming from cultivated land, forest, and grassland respectively. Global SLU has accommodated 34.78 million urban population, and indirectly protected 8922 km2 of flat cultivated land, while causing a net loss of 4373 km2 of green ecological land. Deliberately balancing the dual effects of SLU is crucial for advancing sustainable global urbanization.

6.
Oral Health Prev Dent ; 22: 145-150, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652287

RESUMO

PURPOSE: To determine the caries status in children's deciduous teeth and examine the influence of family oral health behaviours on the caries status. MATERIALS AND METHODS: This cross-sectional study included 329 children aged 3-6 years in rural Heishanzui Township, Hebei Province, China, and used a completely random sampling method. These children underwent physical and oral health examinations. The questionnaires were given to the parents and caregivers of the examined children. RESULTS: The prevalence of caries in the deciduous dentition among children aged 3-6 years was 80.55%, with a dmft index of 4.93. Children in the caries group ate sweets, chocolates, and carbonated drinks more frequently than did children in the caries-free group (p < 0.05). Children in the caries-free group brushed their teeth more frequently, with parents helping their children brush, more often than did those in the caries-affected group (p < 0.05). The level of parental education and annual household income also had statistically significant effects on the prevalence of caries in the two groups (p < 0.05). Logistic regression analysis revealed that the frequency of eating sweets was a risk factor for caries in deciduous teeth (odds ratio = 2.20; p < 0.05). CONCLUSION: The prevalence of caries in deciduous teeth among children aged 3-6 years in rural Heishanzui Township was high. Compared to children in the caries-affected group, the families and children in the caries-free group had better oral hygiene behaviours. Moreover, the frequency of eating sweets was shown to be a risk factor for caries in deciduous teeth in children aged 3-6 years.


Assuntos
Índice CPO , Cárie Dentária , Dente Decíduo , Humanos , Cárie Dentária/epidemiologia , Pré-Escolar , Estudos Transversais , China/epidemiologia , Masculino , Feminino , Criança , Prevalência , Escovação Dentária/estatística & dados numéricos , Escolaridade , Renda , População Rural , Comportamentos Relacionados com a Saúde , Pais , Bebidas Gaseificadas/estatística & dados numéricos , Fatores de Risco
7.
Chemosphere ; 353: 141580, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430943

RESUMO

Information on biotransformation of antivirals in the side-stream partial nitritation (PN) process was limited. In this study, a side-stream PN sludge was adopted to investigate favipiravir biotransformation under controlled ammonium and pH levels. Results showed that free nitrous acid (FNA) was an important factor that inhibited ammonia oxidation and the cometabolic biodegradation of favipiravir induced by ammonia oxidizing bacteria (AOB). The removal efficiency of favipiravir reached 12.6% and 35.0% within 6 days at the average FNA concentrations of 0.07 and 0.02 mg-N L-1, respectively. AOB-induced cometabolism was the sole contributing mechanism to favipiravir removal, excluding AOB-induced metabolism and heterotrophic bacteria-induced biodegradation. The growth of Escherichia coli was inhibited by favipiravir, while the AOB-induced cometabolism facilitated the alleviation of the antimicrobial activities with the formed transformation products. The biotransformation pathways were proposed based on the roughly identified structures of transformation products, which mainly involved hydroxylation, nitration, dehydrogenation and covalent bond breaking under enzymatic conditions. The findings would provide insights on enriching AOB abundance and enhancing AOB-induced cometabolism under FNA stress when targeting higher removal of antivirals during the side-stream wastewater treatment processes.


Assuntos
Amidas , Compostos de Amônio , Pirazinas , Esgotos , Amônia/toxicidade , Amônia/metabolismo , Rios , Oxirredução , Ácido Nitroso , Biotransformação , Antivirais/toxicidade , Reatores Biológicos , Nitritos
8.
Aging (Albany NY) ; 16(1): 43-65, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38206293

RESUMO

Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through in vitro experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Carcinogênese , Carcinógenos , Estresse do Retículo Endoplasmático/genética , Prognóstico , Neoplasias da Próstata/genética
9.
J Mech Behav Biomed Mater ; 150: 106343, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169211

RESUMO

In this paper, inorganic phosphate bonded coatings (IPBCs) via embedding reduced graphene oxide (rGO) modified with heptadecafluoro-1,1,2,2-tetradecyl trimethoxysilane (FAS) were prepared through sol-gel method. Aim of this paper is to research the corrosion resistance of IPBCs with the addition of rGO modified with FAS. Firstly, the Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy (Raman) and surface morphology of GO and rGO modified with and without FAS were characterized. Results indicated that the hydrophobic -CF2- and -CF3 groups were successfully introduced into GO and rGO after modification. And IPBCs with rGO-FAS exhibited higher hydrophobicity and corrosion resistance than IPBCs with the addition of GO or GO-FAS. That is because the hydrophobicity and the introduction of low surface energy material is conducive to overcoming the interaction of rGO itself, thus rGO can be better utilized and played, which resulting the excellent corrosion performance of IPBC@rGO-FAS.


Assuntos
Grafite , Fosfatos , Espectroscopia de Infravermelho com Transformada de Fourier , Corrosão , Grafite/química
10.
J Biosci Bioeng ; 137(1): 38-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37977976

RESUMO

Paraburkholderia terrae strain KU-15 grows on 2- and 4-nitrobenzoate and 2- and 4-aminobenzoate (ABA) as the sole nitrogen and carbon sources. The genes responsible for the potential degradation of 2- and 4-nitrobenzoate and 2-ABA have been predicted from its genome sequence. In this study, we identified the pab operon in P. terrae strain KU-15. This operon is responsible for the 4-ABA degradation pathway, which involves the formation of a γ-glutamylated intermediate. Reverse transcription-polymerase chain reaction revealed that the pab operon was induced by 4-ABA. Herein, studying the deletion of pabA and pabB1 in strain KU-15 and the examining of Escherichia coli expressing the pab operon revealed the involvement of the operon in 4-ABA degradation. The first step of the degradation pathway is the formation of a γ-glutamylated intermediate, whereby 4-ABA is converted to γ-glutamyl-4-carboxyanilide (γ-GCA). Subsequently, γ-GCA is oxidized to protocatechuate. Overexpression of various genes in E. coli and purification of recombinant proteins permitted the functional characterization of relevant pathway proteins: PabA is a γ-GCA synthetase, PabB1-B3 functions in a multicomponent dioxygenase system responsible for γ-GCA dioxygenation, and PabC is a γ-GCA hydrolase that reverses the formation of γ-GCA by PabA.


Assuntos
Ácido 4-Aminobenzoico , para-Aminobenzoatos , para-Aminobenzoatos/metabolismo , Ácido 4-Aminobenzoico/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Família Multigênica , Nitrobenzoatos/metabolismo
11.
Front Nutr ; 10: 1275291, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38130442

RESUMO

Objectives: We aimed to provide a timely, comprehensive, and reliable assessment of the burden of iron deficiency (ID) in children between 1990 and 2019 at the global, regional, and national levels to inform policymakers in developing locally appropriate health policies. Methods: Data related to ID among children younger than 15 years old were analyzed by sex, age, year, socio-demographic index (SDI), and location according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates were used to compare the burden between different regions and countries. Furthermore, the Joinpoint regression model was used to assess temporal trends from 1990 to 2019. Results: In 2019, the number of prevalent cases and disability-adjusted life years (DALYs) for ID in children were 391,491,699 and 13,620,231, respectively. The global age-standardized prevalence and DALY rates for childhood ID in 2019 were 20,146.35 (95% confidence interval: 19,407.85 to 20,888.54) and 698.90 (466.54 to 1015.31) per 100,000, respectively. Over the past 30 years, the global prevalence of ID among children has been highest in low-SDI regions, particularly in Western Sub-Saharan Africa, South Asia, and Eastern Sub-Saharan Africa. Since 1990, the prevalence and DALY of ID in children have been declining in most geographic regions. Nationally, Ecuador, China, and Chile have shown the most significant decreases in prevalence. The greatest decline in age-standardized DALY rate was observed in Ecuador, while Burkina Faso experienced the highest increase. Bhutan had the highest prevalence and DALY rates in 2019. On the age level, the prevalence was relatively higher among the <5 years age group. At the gender dimension, the prevalence of ID in children overall was more pronounced in girls than in boys, as was the case for DALY. Conclusion: Although the burden of ID in children has been declining, this disease remains a major public health problem, especially in countries with low SDI. Children younger than 5 years of age are an important group for whom targeted measures are needed to reduce the burden of ID.

12.
Front Oncol ; 13: 1287653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38115907

RESUMO

Background: The burden of colorectal cancer (CRC) in Europe is at a high level, but the epidemiological features have not yet been systematically studied. This study aimed to provide a timely and reliable assessment of the burden and trends of CRC in Europe to provide a scientific basis for its prevention and treatment. Methods: We analyzed data on CRC in 44 European countries between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019. In addition, the joinpoint regression model was applied to reflect temporal trends. The age-period-cohort model was constructed to explore age, period, and birth cohort effects that influence the risk of morbidity and mortality. Results: In Europe, new cases, disability-adjusted life years (DALYs) and deaths of CRC rose by 70.01%, 22.88% and 38.04% from 1990 to 2019, respectively. The age-standardized incidence rate (ASIR) has increased, while age-standardized DALY rate and age-standardized mortality rate (ASMR) have declined. We found that men experienced a significantly higher CRC burden than women. Age-period-cohort analysis showed that the risk of incidence and mortality increased with age and time; and it was lower in the later-born cohort than the earlier-born cohort. Conclusion: ASIR for CRC in Europe generally trended upwards from 1990 to 2019, stabilizing in recent years but still at a high level. CRC burden varied considerably in different countries. There was a pronounced gender difference in CRC burden, and middle-aged and older men should be a priority population for CRC prevention and treatment.

13.
Aging Clin Exp Res ; 35(12): 3127-3136, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37962764

RESUMO

BACKGROUND AND AIMS: The end of the zero-COVID-19 policy placed a large number of older adults in China at increased risk of COVID-19 infection. SARS-CoV-2 rapid antigen testing (RAT) is a promising tool for scaling up testing and ensuring that patient management and public health measures can be implemented without delay. We aimed to understand the knowledge and willingness of RAT, and its correlates among older adults in China. METHODS: A nationwide cross-sectional survey on knowledge and willingness about RAT among older adults in China was conducted between January 14 and 28, 2023, shortly after the end of the zero-COVID-19 policy. An online questionnaire was used to collect information on sociodemographic characteristics, health characteristics, sources to access RAT information, and attitudes toward COVID-19 and its RAT. Logistic regression was used to assess correlates of knowledge of RAT and willingness to take RAT among older adults. RESULTS: A total of 1030 older adults (494 women and 536 men, mean age 68.7 ± 7.0 years) were recruited. 49.4% of the participants had a high level of RAT knowledge. After adjusting for sociodemographic characteristics, chronic diseases (0.70, 0.49-0.99), learning RAT from new media (5.46, 3.48-8.68) and traditional media (3.35, 2.13-5.34), and perceiving RAT as convenient (4.03, 2.80-5.85) were associated with levels of RAT knowledge. 53.3% of the participants were willing to take RAT. After adjusting for sociodemographic characteristics, learning RAT from new media (8.46, 5.26-14.0) and traditional media (1.63, 1.04-2.55), perceiving RAT as convenient (2.97, 2.10-4.22), and worrying about (re)infection with COVID-19 (2.12, 1.55-2.92) were associated with willingness to take RAT. CONCLUSION: The levels of RAT knowledge and willingness to take RAT among older adults in China may hinder the scale-up of RAT. Health education about RAT should be strengthened among older adults. Special efforts should be made to integrate traditional and new media to promote RAT among older adults, specifically, for virus susceptibility and the convenience of RAT. Given the reopening of society, our study could inform our response to future novel infectious diseases and aid in the timely scale-up of RAT.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Transversais , Inquéritos e Questionários , China
14.
Int J Colorectal Dis ; 38(1): 245, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37787806

RESUMO

BACKGROUND: Intestinal obstruction (IO) is a common surgical acute abdominal condition that places a significant burden on modern health systems. Unfortunately, the global burden and trends of IO remain unknown. Therefore, this study aimed to comprehensively assess its long-term trends and epidemiological features, which will help policymakers to formulate appropriate health policies. METHODS: We conducted an ecological study using data from the Global Burden of Disease Study (GBD) 2019. Data on IO were analyzed by sex, age, year, sociodemographic index (SDI), and location according to GBD 2019. In addition, joinpoint regression analysis was used to assess temporal trends. Age-period-cohort analysis (APC Analysis) was conducted to evaluate age, period, and birth cohort effects on IO incidence and mortality risk. RESULTS: Globally, the prevalent and incident cases increased by 56.91% and 86.67% from 1990 to 2019, respectively. Joinpoint regression analysis showed that age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased, but age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year (DALY) rate decreased over the past three decades. The age effect demonstrated that older people have a higher risk of morbidity and mortality. The period effect of incidence and mortality showed an upward trend from 1990 to 2019. Cohort effect revealed that the incidence and death risk peaked in the earlier-born cohort and was lower in the more recent-born cohort. Notably, we found that the burden of IO was higher in males than in females throughout the study period. There are huge disparities in IO burden among countries. CONCLUSION: Globally, the reported incidence and prevalence of IO increased from 1990 to 2019. The burden of IO differed markedly by age, sex, country, and region. Middle-aged and elderly people over 50 years old were at high risk. Given the ageing population, the burden of IO will be a major public health challenge. Thus, there is a strong necessity to strengthen prevention and early intervention in the at-risk population.


Assuntos
Carga Global da Doença , Obstrução Intestinal , Idoso , Feminino , Masculino , Pessoa de Meia-Idade , Humanos , Política de Saúde
15.
Entropy (Basel) ; 25(8)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37628202

RESUMO

The improper Gaussian signaling (IGS) technique can improve the achievable rate of an interference-limited network by fully exploiting the second-order statistics of complex signaling. This paper addresses the outage performance analysis of a two-user downlink non-orthogonal multiple access (NOMA) system using the IGS technique in the presence of imperfect successive interference cancellation (SIC). The strong channel user (SU) adopts the IGS, while the weak channel user (WU) adopts the traditional proper Gaussian signaling (PGS). Considering a practical scenario where the transmitter has obtained the statistics of the channel coefficients instead of the instantaneous channel state information (CSI), the expressions of the achievable rates of both users under residual interference due to imperfect SIC are derived, together with their outage probabilities, subject to predetermined target rates and channel statistics. Given a fixed transmit power of the WU, both the transmit power and the degree of impropriety of the SU are optimized to minimize the outage probability subject to the outage constraint of the WU. Numerical results are provided to assess the benefits of the proposed IGS-based downlink NOMA system, which are consistent with the analysis.

16.
Front Oncol ; 13: 1109037, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397378

RESUMO

Background: Glioblastoma (GBM) is adults' most common and fatally malignant brain tumor. The heterogeneity is the leading cause of treatment failure. However, the relationship between cellular heterogeneity, tumor microenvironment, and GBM progression is still elusive. Methods: Integrated analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (stRNA-seq) of GBM were conducted to analyze the spatial tumor microenvironment. We investigated the subpopulation heterogeneity of malignant cells through gene set enrichment analyses, cell communications analyses, and pseudotime analyses. Significantly changed genes of the pseudotime analysis were screened to create a tumor progress-related gene risk score (TPRGRS) using Cox regression algorithms in the bulkRNA-sequencing(bulkRNA-seq) dataset. We combined the TPRGRS and clinical characteristics to predict the prognosis of patients with GBM. Furthermore, functional analysis was applied to uncover the underlying mechanisms of the TPRGRS. Results: GBM cells were accurately charted to their spatial locations and uncovered their spatial colocalization. The malignant cells were divided into five clusters with transcriptional and functional heterogeneity, including unclassified malignant cells and astrocyte-like, mesenchymal-like, oligodendrocytes-progenitor-like, and neural-progenitor-like malignant cells. Cell-cell communications analysis in scRNA-seq and stRNA-seq identified ligand-receptor pairs of the CXCL, EGF, FGF, and MIF signaling pathways as bridges implying that tumor microenvironment may cause malignant cells' transcriptomic adaptability and disease progression. Pseudotime analysis showed the differentiation trajectory of GBM cells from proneural to mesenchymal transition and identified genes or pathways that affect cell differentiation. TPRGRS could successfully divide patients with GBM in three datasets into high- and low-risk groups, which was proved to be a prognostic factor independent of routine clinicopathological characteristics. Functional analysis revealed the TPRGRS associated with growth factor binding, cytokine activity, signaling receptor activator activity functions, and oncogenic pathways. Further analysis revealed the association of the TPRGRS with gene mutations and immunity in GBM. Finally, the external datasets and qRT-PCR verified high expressions of the TPRGRS mRNAs in GBM cells. Conclusion: Our study provides novel insights into heterogeneity in GBM based on scRNA-seq and stRNA-seq data. Moreover, our study proposed a malignant cell transition-based TPRGRS through integrated analysis of bulkRNA-seq and scRNA-seq data, combined with the routine clinicopathological evaluation of tumors, which may provide more personalized drug regimens for GBM patients.

17.
J Biosci Bioeng ; 136(3): 223-231, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37344279

RESUMO

Little is currently known about the metabolism of the industrial pollutant 2,4-dinitrophenol (DNP), particularly among gram-negative bacteria. In this study, we identified two non-contiguous genetic loci spanning 22 kb of Paraburkholderia (formerly Burkholderia) sp. strain KU-46. Additionally, we characterized four key initial genes (dnpA, dnpB, and dnpC1C2) responsible for DNP degradation, providing molecular and biochemical evidence for the degradation of DNP via the formation of 4-nitrophenol (NP), a pathway that is unique among DNP utilizing bacteria. Reverse transcription polymerase chain reaction (PCR) analysis indicated that dnpA, which encodes the initial hydride transferase, and dnpB which encodes a nitrite-eliminating enzyme, were induced by DNP and organized in an operon. Moreover, we purified DnpA and DnpB from recombinant Escherichia coli to demonstrate their effect on the transformation of DNP to NP through the formation of a hydride-Meisenheimer complex of DNP, designated as H--DNP. The function of DnpB appears new since all homologs of the DnpB sequences in the protein database are annotated as putative nitrate ABC transporter substrate-binding proteins. The gene cluster responsible for the degradation of DNP after NP formation was designated dnpC1C2DXFER, and DnpC1 and DnpC2 were functionally characterized as the FAD reductase and oxygenase components of the two-component DNP monooxygenase, respectively. By elucidating the hqdA1A2BCD gene cluster, we are now able to delineate the final degradation pathway of hydroquinone to ß-ketoadipate before it enters the tricarboxylic acid cycle.


Assuntos
2,4-Dinitrofenol , Oxigenases de Função Mista , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , 2,4-Dinitrofenol/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , Clonagem Molecular , Família Multigênica , Biodegradação Ambiental
19.
Chem Biodivers ; 20(6): e202300448, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37218541

RESUMO

Two previously undescribed compounds (1 and 2) were isolated from Clinopodium polycephalum, a medicinal plant distributed in southwestern and eastern China. Their structures were elucidated using MS analyses and extensive 2D-homo and heteronuclear NMR data interpretations. Both compounds 1 and 2 could significantly shorten APTT and PT, and their procoagulant effect was comparable to that of positive drugs. At the same time, compound 2 had certain antioxidant activity (IC50 value of 2.25±0.05 µM in ABTS assay).


Assuntos
Lamiaceae , Plantas Medicinais , Anticoagulantes/farmacologia , Lamiaceae/química , Antioxidantes/farmacologia , Antioxidantes/química , China , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estrutura Molecular
20.
J Hazard Mater ; 448: 130911, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36860033

RESUMO

Microplastics and nanoplastics (MNPs) have attracted much attention since their wide distribution in the environment and organisms. MNPs in the environment adsorb other organic pollutants, such as Perfluorooctane sulfonate (PFOS), and cause combined effects. However, the impact of MNPs and PFOS in agricultural hydroponic systems is unclear. This study investigated the combined effects of polystyrene (PS) MNPs and PFOS on soybean (Glycine max) sprouts, which are common hydroponic vegetable. Results demonstrated that the adsorption of PFOS on PS particles transformed free PFOS into adsorbed state and reduced its bioavailability and potential migration, thus attenuating acute toxic effects such as oxidative stress. TEM and Laser confocal microscope images showed that PS nanoparticles uptake in sprout tissue was enhanced by the adsorption of PFOS which is because of changes of the particle surface properties. Transcriptome analysis showed that PS and PFOS exposure promoted soybean sprouts to adapt to environmental stress and MARK pathway might play an important role in recognition of microplastics coated by PFOS and response to enhancing plant resistance. This study provided the first evaluation about the effect of adsorption between PS particles and PFOS on their phytotoxicity and bioavailability, in order to provide new ideas for risk assessment.


Assuntos
Glycine max , Microplásticos , Disponibilidade Biológica , Plásticos , Poliestirenos
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