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1.
J Cell Mol Med ; 28(3): e18100, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38189641

RESUMO

IL12B encodes the shared p40 subunit (IL-12p40) of IL-12 and IL-23, which have diverse immune functions and are closely related to the occurrence and development of atherosclerosis (AS). However, the exact role of IL12B in coronary heart disease (CHD) was still unknown. A case-control association analysis was performed between five single nucleotide polymorphisms (SNPs) of IL12B (rs1003199, rs3212219, rs2569254, rs2853694 and rs3212227) and CHD in Chinese Han population (1824 patients with CHD vs. 2784 controls). Logistic regression analyses were used to study the relationships between SNPs and CHD, while multiple linear regression analyses were used to test the association between the SNP and the severity of CHD. In addition, the plasma IL12B concentration of CHD patients were detected by ELISA. We detected a significant association between one of the SNPs, rs2853694-G and CHD (padj = 2.075 × 10-5 , OR, 0.773 [95% CI, 0.686-0.870]). Stratified analysis showed that rs2853694 was associated with CHD in both male and female populations and was significantly associated with both early- and late-onset CHD. In addition, rs2853694 is also related to the different types of CHD including clinical-CHD and anatomical-CHD. Moreover, there are significant differences in serum IL12B concentrations between rs2853694-TT carriers and rs2853694-GT carriers in CHD patients (p = 0.010). A common variant of IL12B was found significantly associated with CHD and its subgroups. As a shared subunit of IL-12 and IL-23, IL-12p40 may play a key role in IL-12/IL-23 axis mediated AS, which is expected to be an effective therapeutic target for CHD.


Assuntos
Aterosclerose , Doença das Coronárias , Humanos , Masculino , Feminino , Predisposição Genética para Doença , Subunidade p40 da Interleucina-12 , Interleucina-12 , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Genótipo
2.
Food Microbiol ; 117: 104387, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37919011

RESUMO

Ultrasonic treatment is widely used for surface cleaning of vegetables in the processing of agricultural products. In the present study, the molecular and proteomic response of Pseudomonas fluorescens biofilm cultured on lettuce was investigated after ultrasound treatment at different intensity levels. The results show that the biofilm was efficiently removed after ultrasound treatment with intensity higher than 21.06 W/cm2. However, at an intensity of less than 18.42 W/cm2, P. fluorescens was stimulated by ultrasound leading to promoted bacterial growth, extracellular protease activity, extracellular polysaccharide secretion (EPS), and synthesis of acyl-homoserine lactones (AHLs) as quorum-sensing signaling molecules. The expression of biofilm-related genes, stress response, and dual quorum sensing system was upregulated during post-treatment ultrasound. Proteomic analysis showed that ultrasound activated proteins in the flagellar system, which led to changes in bacterial tendency; meanwhile, a large number of proteins in the dual-component system began to be regulated. ABC transporters accelerated the membrane transport of substances inside and outside the cell membrane and equalized the permeability conditions of the cell membrane. In addition, the expression of proteins related to DNA repair was upregulated, suggesting that bacteria repair damaged DNA after ultrasound exposure.


Assuntos
Lactuca , Pseudomonas fluorescens , Pseudomonas fluorescens/fisiologia , Proteômica , Biofilmes , Percepção de Quorum
3.
Arch Gynecol Obstet ; 310(1): 181-194, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782764

RESUMO

PURPOSE: The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. METHODS: We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. RESULTS: CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. CONCLUSION: For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined.


Assuntos
Agenesia do Corpo Caloso , Humanos , Estudos Retrospectivos , Feminino , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/diagnóstico , Gravidez , Adulto , Análise em Microsséries , Diagnóstico Pré-Natal , Sequenciamento do Exoma , Aberrações Cromossômicas/embriologia , Aberrações Cromossômicas/estatística & dados numéricos , Ultrassonografia Pré-Natal
4.
Int J Mol Sci ; 25(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39125959

RESUMO

Glucagon receptor (GCGR) is a class B1 G-protein-coupled receptor that plays a crucial role in maintaining human blood glucose homeostasis and is a significant target for the treatment of type 2 diabetes mellitus (T2DM). Currently, six small molecules (Bay 27-9955, MK-0893, MK-3577, LY2409021, PF-06291874, and LGD-6972) have been tested or are undergoing clinical trials, but only the binding site of MK-0893 has been resolved. To predict binding sites for other small molecules, we utilized both the crystal structure of the GCGR and MK-0893 complex and dynamic conformations. We docked five small molecules and selected the best conformation based on binding mode, docking score, and binding free energy. We performed MD simulations to verify the binding mode of the selected small molecules. Moreover, when selecting conformations, results of competitive binding were referred to. MD simulation indicated that Bay 27-9955 exhibits moderate binding stability in Pocket 3. MK-3577, LY2409021, and PF-06291874 exhibited highly stable binding to Pocket 2, consistent with experimental results. However, LY2409021 may also bind to Pocket 5. Additionally, LGD-6972 exhibited relatively stable binding in Pocket 5. We also conducted structural modifications of LGD-6972 based on the results of MD simulations and predicted its analogues' bioavailability, providing a reference for the study of GCGR small molecules.


Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação Proteica , Receptores de Glucagon , Sítios de Ligação , Humanos , Cristalografia por Raios X , Receptores de Glucagon/química , Receptores de Glucagon/metabolismo , Ligação Proteica , Bibliotecas de Moléculas Pequenas/química , Ligantes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo
5.
Int J Biol Macromol ; 260(Pt 2): 129614, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246468

RESUMO

The potential application of succinylated chickpea protein (SCP) as a wall material for spray-dried microencapsulated probiotics was investigated. The results showed that succinylation increased the surface charge of chickpea proteins (CP) and reduced the particle size of the proteins. Meanwhile, succinylated modification decreased the solubility of protein under acidic conditions and increased the solubility in alkaline conditions. The effects of spray drying and in vitro gastrointestinal digestion on probiotics were investigated by microencapsulating chickpea protein with different degrees of N-succinylation. The results showed that all microcapsules had similar morphology, particle size and low water content. The microcapsules prepared by succinylated chickpea protein showed better stability and viability during spray drying and gastrointestinal digestion. The protective effect of probiotics was better as the degree of N-succinylation increased. In particular, the SCP-3-P sample (10 % succinic anhydride modified CP and maltodextrin) lost only 0.29 Log CFU/g throughout gastrointestinal digestion. The superior protective effect provided by succinylated CP in simulated gastric fluid (SGF) was mainly attributed to the reaction of succinic anhydride with protein to cause protein aggregation under gastric acidic conditions, reducing the infiltration of gastric acid and pepsin and maintaining the structural integrity of the microcapsules. Therefore, these findings provide a new strategy for probiotic intestinal delivery and application of chickpea protein.


Assuntos
Cicer , Probióticos , Anidridos Succínicos , Composição de Medicamentos/métodos , Cápsulas/química , Probióticos/química , Digestão , Viabilidade Microbiana
6.
J Health Popul Nutr ; 43(1): 58, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725055

RESUMO

BACKGROUND: The COVID-19 pandemic has profoundly affected human social contact patterns, but there is limited understanding regarding the post-pandemic social contact patterns. Our objective is to quantitatively assess social contact patterns in Suzhou post-COVID-19. METHODS: We employed a diary design and conducted social contact surveys from June to October 2023, utilizing paper questionnaires. A generalized linear model was utilized to analyze the relationship between individual contacts and covariates. We examined the proportions of contact type, location, duration, and frequency. Additionally, age-related mixed matrices were established. RESULTS: The participants reported an average of 11.51 (SD 5.96) contact numbers and a total of 19.78 (SD 20.94) contact numbers per day, respectively. The number of contacts was significantly associated with age, household size, and the type of week. Compared to the 0-9 age group, those in the 10-19 age group reported a higher number of contacts (IRR = 1.12, CI: 1.01-1.24), while participants aged 20 and older reported fewer (IRR range: 0.54-0.67). Larger households (5 or more) reported more contacts (IRR = 1.09, CI: 1.01-1.18) and fewer contacts were reported on weekends (IRR = 0.95, CI: 0.90-0.99). School had the highest proportion of contact durations exceeding 4 h (49.5%) and daily frequencies (90.4%), followed by home and workplace. The contact patterns exhibited clear age-assortative mixing, with Q indices of 0.27 and 0.28. CONCLUSIONS: We assessed the characteristics of social contact patterns in Suzhou, which are essential for parameterizing models of infectious disease transmission. The high frequency and intensity of contacts among school-aged children should be given special attention, making school intervention policies a crucial component in controlling infectious disease transmission.


Assuntos
COVID-19 , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , China/epidemiologia , Feminino , Masculino , Adulto , Adolescente , Criança , Adulto Jovem , Pré-Escolar , Pessoa de Meia-Idade , Lactente , Busca de Comunicante/métodos , Inquéritos e Questionários , SARS-CoV-2 , Recém-Nascido , Características da Família , Pandemias , Idoso , Doenças Transmissíveis/transmissão , Doenças Transmissíveis/epidemiologia
7.
Biopreserv Biobank ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38452333

RESUMO

Objective: Amniotic fluid (AF) plays a crucial role in diagnosing and predicting perinatal diseases, specifically preeclampsia (PE). Adequate preservation of AF samples is essential for advancing the development of PE-related biomarkers and understanding the disease's mechanisms. Materials and Methods: This study presents a method for preserving proteins in AF on a solid medium, specifically a nitrocellulose membrane, which is referred to as an AF membrane. Samples were collected from normotensive subjects and PE patients and treated with direct freezing and the AF membrane methods, respectively. Protein quality was assessed through sodium dodecyl sulfate-page and capillary electrophoresis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) with data-independent acquisition was employed for proteomic analysis. Bioinformatics analysis identified differentially expressed proteins and pathways distinguishing normotensive subjects from PE patients. Results: Comparison of the AF membrane method to the direct freezing method showed no significant impact on the protein content in the AF. The preservation methods employed did not result in evident protein differences or degradation in the AF obtained from both normotensive subjects and PE patients. Analysis based on Gene Ontology and HALLMARK gene sets revealed the upregulation of pathways associated with angiotensin, reactive oxygen species, and coagulation in PE patients. Furthermore, several biomarkers previously reported to be increased in PE serum, namely ENG, ERN1, FLT1, GDF15, HSPA5, LGALS3, PAPPA, PTX3, and SERPINE1, were significantly elevated in the AF. Conclusion: The AF membrane method proved to be highly effective, reliable, and durable for preserving proteins in AF samples. Preserving AF samples in a solid state holds significant value in discovering novel protein biomarkers and investigating the underlying mechanisms of PE.

8.
Int J Biol Macromol ; 261(Pt 2): 129838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307428

RESUMO

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis.


Assuntos
Halomonas , Ácidos Pentanoicos , Poli-Hidroxialcanoatos , Halomonas/genética , Halomonas/metabolismo , Carbono/metabolismo , Amido/metabolismo , Hidroxibutiratos/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , Poliésteres/metabolismo
9.
Sci Total Environ ; 926: 171683, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38492593

RESUMO

The upstream cascade dams play an essential role in the nutrient cycle in the Yangtze. However, there is little quantitative information on the effects of upstream damming on nutrient retention in the Three Gorges Reservoir (TGR) in China. Here, we aim to assess the impact of increasing cascade dams in the upstream area of the Yangtze on Dissolved Inorganic Nitrogen and Phosphorus (DIN and DIP) inputs to the TGR and their retention in the TGR and to draw lessons for other large reservoirs. We implemented the Model to Assess River Inputs of Nutrients to seAs (MARINA-Nutrients China-2.0 model). We ran the model with the baseline scenario in which river damming was at the level of 2009 (low) and alternative scenarios with increased damming. Our scenarios differed in nutrient management. Our results indicated that total water storage capacity increased by 98 % in the Yangtze upstream from 2009 to 2022, with 17 new large river dams (>0.5 km3) constructed upstream of the Yangtze. As a result of these new dams, the total DIN inputs to the TGR decreased by 15 % (from 768 Gg year-1 to 651 Gg year-1) and DIP inputs decreased by 25 % (from 70 Gg year-1 to 53 Gg year-1). Meanwhile, the molar DIN:DIP ratio in inputs to the TGR increased by 13 % between 2009 and 2022. In the future, DIN and DIP inputs to the TGR are projected to decrease further, while the molar DIN:DIP ratio will increase. The Upper Stem contributed 39 %-50 % of DIN inputs and 63 %-84 % of DIP inputs to the TGR in the past and future. Our results deepen our knowledge of nutrient loadings in mainstream dams caused by increasing cascade dams. More research is needed to understand better the impact of increased nutrient ratios due to dam construction.

10.
Sci Total Environ ; 918: 170690, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38325478

RESUMO

Worldwide, anthropogenic activities threaten surface water quality by aggravating eutrophication and increasing total nitrogen to total phosphorus (TN:TP) ratios. In hydrologically connected systems, water quality management may benefit from in-ecosystem nutrient retention by preventing nutrient transport to downstream systems. However, nutrient retention may also alter TN:TP ratios with unforeseen consequences for downstream water quality. Here, we aim to increase understanding of how nutrient retention may influence nutrient transport to downstream systems to improve long-term water quality management. We analyzed lake ecosystem state, in-lake nutrient retention, and nutrient transport (ratios) for 3482 Chinese lakes using the lake process-based ecosystem model PCLake+. We compared a low climate change and sustainability-, and a high climate change and economy-focused scenario for 2050 against 2012. In both scenarios, the effect of nutrient input reduction outweighs that of temperature rise, resulting in more lakes with good ecological water quality (i.e., macrophyte-dominated) than in 2012. Generally, the sustainability-focused scenario shows a more promising future for water quality than the economy-focused scenario. Nevertheless, most lakes remain phytoplankton-dominated. The shift to more macrophyte-dominated lakes in 2050 is accompanied by higher nutrient retention fractions and less nutrient transport to downstream waterbodies. In-lake nutrient retention also alters the water's TN:TP ratio, depending on the inflow TN:TP ratio and the ecosystem state. In 2050 higher TN:TP ratios are expected in the outflows of lakes than in 2012, especially for the sustainability-focused scenario with strong TP loading reduction. However, the downstream impact of increased TN:TP ratios depends on actual nutrient loadings and the limiting nutrient in the receiving system. We conclude that nutrient input reductions, improved water quality, higher in-lake nutrient retention fractions, and lower nutrient transport to downstream waterbodies go hand in hand. Therefore, water quality management could benefit even more from nutrient pollution reduction than one would expect at first sight.

11.
Heliyon ; 10(8): e28257, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655314

RESUMO

In this work, magnetic molecularly imprinted polymers (MIPs) for specific recognition of Hydroxytyrosol (HT) were designed by vinyl-modified magnetic particles (Fe3O4@SiO2@VTEOs) as carrier, ternary deep eutectic solvent (DES) as functional monomer, while ethylene glycol dimethacrylate (EGDMA) as crosslinker. The optimum amount of DES was obtained by adsorption experiments (molar ratio, caffeic acid: choline chloride: formic acid = 1:6:3) which were 140 µL in total. Under the optimized amount of DES, the maximum adsorption capacity of the MIPs particles was 42.43 mg g-1, which was superior to non-imprinted polymer (4.64 mg g-1) and the imprinting factor (IF) is 9.10. Syringin and Oleuropicrin were used as two reference molecules to test the selectivity of the DES-MIPs particles. The adsorption capacity of HT was 40.11 mg g-1. Three repeated experiments show that the polymer has high stability and repeatability (RSD = 5.50).

12.
Nat Food ; 5(6): 499-512, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849568

RESUMO

The contribution of crop and livestock production to the exceedance of the planetary boundary for phosphorus (P) in China is still unclear, despite the country's well-known issues with P fertilizer overuse and P-related water pollution. Using coupled models at sub-basin scales we estimate that livestock production increased the consumption of P fertilizer fivefold and exacerbated P losses twofold from 1980 to 2017. At present, China's crop-livestock system is responsible for exceeding what is considered a 'just' threshold for fertilizer P use by 30% (ranging from 17% to 68%) and a 'safe' water quality threshold by 45% (ranging from 31% to 74%) in 25 sub-basins in China. Improving the crop-livestock system will keep all sub-basins within safe water quality and just multigenerational limits for P in 2050.


Assuntos
Produtos Agrícolas , Fertilizantes , Fósforo , Fósforo/análise , China , Produtos Agrícolas/crescimento & desenvolvimento , Animais , Fertilizantes/análise , Gado , Agricultura/métodos , Qualidade da Água
13.
Nat Commun ; 15(1): 880, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321008

RESUMO

Water security is at stake today. While climate changes influence water availability, urbanization and agricultural activities have led to increasing water demand as well as pollution, limiting safe water use. We conducted a global assessment of future clean-water scarcity for 2050s by adding the water pollution aspect to the classical water quantity-induced scarcity assessments. This was done for >10,000 sub-basins focusing on nitrogen pollution in rivers by integrating land-system, hydrological and water quality models. We found that water pollution aggravates water scarcity in >2000 sub-basins worldwide. The number of sub-basins with water scarcity triples due to future nitrogen pollution worldwide. In 2010, 984 sub-basins are classified as water scarce when considering only quantity-induced scarcity, while 2517 sub-basins are affected by quantity & quality-induced scarcity. This number even increases to 3061 sub-basins in the worst case scenario in 2050. This aggravation means an extra 40 million km2 of basin area and 3 billion more people that may potentially face water scarcity in 2050. Our results stress the urgent need to address water quality in future water management policies for the Sustainable Development Goals.

14.
Nat Commun ; 15(1): 1355, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355596

RESUMO

Interstitial iodides are the most critical type of defects in perovskite solar cells that limits efficiency and stability. They can be generated during solution, film, and device processing, further accelerating degradation. Herein, we find that introducing a small amount of a zinc salt- zinc trifluoromethane sulfonate (Zn(OOSCF3)2) in the perovskite solution can control the iodide defects in resultant perovskites ink and films. CF3SOO̶ vigorously suppresses molecular iodine formation in the perovskites by reducing it to iodide. At the same time, zinc cations can precipitate excess iodide by forming a Zn-Amine complex so that the iodide interstitials in the resultant perovskite films can be suppressed. The perovskite films using these additives show improved photoluminescence quantum efficiency and reduce deep trap density, despite zinc cations reducing the perovskite grain size and iodide interstitials. The zinc additives facilitate the formation of more uniform perovskite films on large-area substrates (78-108 cm2) in the blade-coating process. Fabricated minimodules show power conversion efficiencies of 19.60% and 19.21% with aperture areas of 84 and 108 cm2, respectively, as certified by National Renewable Energy Laboratory (NREL), the highest efficiency certified for minimodules of these sizes.

15.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167355, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39009172

RESUMO

BACKGROUND: HOIP is the catalytic subunit of the E3 ligase complex (linear ubiquitin chain assembly complex), which is able to generate linear ubiquitin chains. However, the role of rare HOIP functionally deficient variants remains unclear. The pathogenic mechanism and the relationship with immune deficiency phenotypes remain to be clarified. METHODS: Based on a next-generation sequencing panel of 270 genes, we identified a HOIP deletion variant that causes common variable immunodeficiency disease. Bioinformatics analysis and cell-based experiments were performed to study the molecular mechanism by which the variant causes immunodeficiency diseases. FINDINGS: A homozygous loss-of-function variant in HOIP was identified. The variant causes a frameshift and generates a premature termination codon in messenger RNA, resulting in a C-terminal truncated HOIP mutant, that is, the loss of the linear ubiquitin chain-specific catalytic domain. The truncated HOIP mutant has impaired E3 ligase function in linear ubiquitination, leading to the suppression of canonical NF-κB signalling and increased TNF-induced multiple forms of cell death. INTERPRETATION: The loss-of-function HOIP variant accounts for the immune deficiencies. The canonical NF-κB pathway and cell death are involved in the pathogenesis of the disease. FUNDING: This study was funded by the National Natural Science Foundation of China (No. 82270444 and 81501851). RESEARCH IN CONTEXT: Evidence before this study LUBAC is the only known linear ubiquitin chain assembly complex for which HOIP is an essential catalytic subunit. Three HOIP variants have now been identified in two immunodeficient patients and functionally characterised. However, there have been no reports on the pathogenicity of only catalytic domain deletion variants in humans, or the pathogenic mechanisms of catalytic domain deletion variants. Added value of this study We report the first case of an autosomal recessive homozygous deletion variant that results in deletion of the HOIP catalytic structural domain. We demonstrate that this variant is a loss-of-function variant using a heterologous expression system. The variant has impaired E3 ligase function. It can still bind to other subunits of LUBAC, but it fails to generate linear ubiquitin chains. We also explored the underlying mechanisms by which this variant leads to immunodeficiency. The variant attenuates the canonical NF-κB and MAPK signalling cascades and increases the sensitivity of TNFα-induced diverse cell death and activation of mitochondrial apoptosis pathways. These findings provide support for the treatment and drug development of patients with inborn errors of immunity in HOIP and related signalling pathways. Implications of all the available evidence First, this study expands the HOIP pathogenic variant database and phenotypic spectrum. Furthermore, studies on the biological functions of pathogenic variants in relation to the NF-κB signalling pathway and cell death provided new understanding into the genetic basis and pathogenesis of HOIP-deficient immune disease, indicating the necessity of HOIP and related signalling pathway variants as diagnostic targets in patients with similar genetic deficiency phenotypes..


Assuntos
Mutação da Fase de Leitura , NF-kappa B , Transdução de Sinais , Fator de Necrose Tumoral alfa , Ubiquitina-Proteína Ligases , Feminino , Humanos , Masculino , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Células HEK293 , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Criança , Linhagem
16.
Science ; 384(6700): 1126-1134, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38843338

RESUMO

The light-emitting diodes (LEDs) used in indoor testing of perovskite solar cells do not expose them to the levels of ultraviolet (UV) radiation that they would receive in actual outdoor use. We report degradation mechanisms of p-i-n-structured perovskite solar cells under unfiltered sunlight and with LEDs. Weak chemical bonding between perovskites and polymer hole-transporting materials (HTMs) and transparent conducting oxides (TCOs) dominate the accelerated A-site cation migration, rather than direct degradation of HTMs. An aromatic phosphonic acid, [2-(9-ethyl-9H-carbazol-3-yl)ethyl]phosphonic acid (EtCz3EPA), enhanced bonding at the perovskite/HTM/TCO region with a phosphonic acid group bonded to TCOs and a nitrogen group interacting with lead in perovskites. A hybrid HTM of EtCz3EPA with strong hole-extraction polymers retained high efficiency and improved the UV stability of perovskite devices, and a champion perovskite minimodule-independently measured by the Perovskite PV Accelerator for Commercializing Technologies (PACT) center-retained operational efficiency of >16% after 29 weeks of outdoor testing.

17.
Behav Sci (Basel) ; 13(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38131847

RESUMO

This study aimed to investigate the factors influencing career expectations, determine the influence of college students' personal ability on personal evaluation in the process of gaining employment, and further explore the impact of personal evaluation and social support on career expectations. This study used a random sampling method to administer questionnaires to final-year undergraduates majoring in the liberal arts, science, art, and sports at two Chinese universities. Career expectations were positively correlated with satisfaction. The preferred employer for graduates is a school. In selecting a career, college students believed that exerting their talents was most important. Personal evaluations had a significant effect on self-development in career expectations. The level of social support had a significant effect on prestige and welfare stability in career expectations.

18.
Front Hum Neurosci ; 17: 1326602, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162286

RESUMO

Intonation is the variation in pitch used in speech, which forms the premise of tonal and non-tonal languages. Interrogative words are words that introduce questions. Previous research lacks clarity regarding the specific cues used in the processing of word intonation. To address this gap, this study used the event-related potential electroencephalogram (EEG) research method to explore the intonation processing of tone two (mid-rising) interrogative words in Mandarin. For this, the word "shui," meaning "who," was selected as the experimental material. To avoid the influence of the environment, gender, and semantics, the Hum version, corresponding to the stimulus material, was also adopted for the experiment. This study used a passive oddball paradigm to examine the clues of intonation information processing in automatic cognitive processing through amplitude, latency, time window, and evoked location potential mismatch negativity. The standard stimulus was the declarative intonation with a high probability of occurrence (90%), and the deviant stimulus was the interrogative intonation with a low probability of occurrence (10%). In the time window of 370-450 ms, the mismatch negativity was found at the F3, F4, C3, Cz, and C4 channels. The findings show that, in the passive oddball paradigm, lexical semantics are essential for intonation processing at the pre-attentive level, which is dominated by the frontal and central areas of the brain. The results support the functional and comprehensive hypotheses that the processing of intonation is based on the function of language and that bilateral regions are involved in this processing. This study makes an important contribution by providing event-related potential evidence that lexical semantics plays a key role in the pre-attentive processing of intonation, as shown by the significant differences between semantic and non-semantic conditions.

19.
Eur J Dermatol ; 33(5): 487-494, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297924

RESUMO

The management of melasma is challenging. Platelet-rich plasma (PRP) therapy has been shown to be beneficial, however, the use of anticoagulants for PRP is dangerous. To evaluate the efficacy of recently developed blood-derived biomaterials (injectable platelet-rich fibrin [I-PRF]) in a rat model of melasma. Sprague Dawley (SD) rats were used to replicate an experimental animal model of melasma. SD rats exhibiting melasma were randomly divided into experimental and control groups. The experimental group was administered weekly intradermal injections of I-PRF, whereas the control group received an equivalent amount of saline. After four weeks, back skin was removed and evaluated based on (1) gross observation, (2) pathological examination and imaging analysis, and (3) biochemical detection. Data were analysed using SAS9.4 software. I-PRF, a safe blood product without anticoagulants, inhibited melanin production in the epidermis and reduced oxidative stress damage in the cortex, improving melasma. I-PRF is a safe and cost-effective blood-derived biomaterial which is useful for the treatment of melasma.


Assuntos
Melanose , Fibrina Rica em Plaquetas , Plasma Rico em Plaquetas , Animais , Ratos , Anticoagulantes , Melanose/tratamento farmacológico , Ratos Sprague-Dawley
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