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1.
Environ Sci Technol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632926

RESUMO

Coumarin was detected as one of the most abundant compounds by nontargeted analysis of natural product components in actual water samples prior to disinfection. More importantly, prechlorination of humic acid generated 3-hydroxycoumarin and monohydroxy-monomethyl-substituted coumarin with a total yield of ≤10.1%, which suggested the humic substance in raw water is an important source of coumarins. 7-Hydroxycoumarin, 6-hydroxy-4-methylcoumarin, 6,7-dihydroxycoumarin, and 7-methoxy-4-methylcoumarin were identified in raw water by high-performance liquid chromatography-tandem high-resolution mass spectrometry because only some coumarin standards were commercially available. Their chlorination generated monochlorinated and polychlorinated coumarins, and their structures were confirmed by the synthesized standards. These products could form at various dosages of chlorine and pH levels, and some with a concentration of 600 ng/L can be stable in tap water for days. 3,6,8-Trichloro-7-hydroxycoumarin, 3-chloro-7-methoxy-4-methylcoumarin, and 3,6-dichloro-7-methoxy-4-methylcoumarin were first identified in finished water with concentrations of 0.0670, 78.1, and 14.7 ng/L, respectively, but not in source water, suggesting that they are new DBPs formed during disinfection. The cytotoxicity of 3-chloro-7-methoxy-4-methylcoumarin in CHO-K1 cells was comparable to those of 2,6-dibromo-1,4-benzoquinone and 2,6-dichloro-1,4-benzoquinone in TIC-Tox analyses, suggesting that further investigation of their occurrence and control in drinking water systems is warranted.

2.
Phytomedicine ; 128: 155589, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38608487

RESUMO

BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.

3.
Mikrochim Acta ; 191(5): 269, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630309

RESUMO

A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition. With increasing amount of FPT the ECL signal decreased. Under the optimum conditions, the ECL response was linearly related to the logarithm of FPT concentration. The developed ECL sensor allowed for sensitive determination of FPT and exhibited a wide linear range from 1.0 × 10- 10 mol L- 1 to 1.0 × 10- 6 mol L- 1. The limit of detection was 3.3 × 10- 11 mol L- 1 (S/N = 3). It can be used for the detection of FPT in vegetable samples.


Assuntos
Luminescência , Impressão Molecular , Piretrinas , Luminol , Polímeros Molecularmente Impressos
4.
BMC Womens Health ; 24(1): 225, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582833

RESUMO

OBJECTIVE: Although oxidative stress is a recognized factor of inflammation, the correlation between oxidative balance score (OBS), a biomarker indicating the balance of oxidation and antioxidant, and rheumatoid arthritis (RA), an immune system disease that tends to occur in women, remains unexplored. Hence, the aim of this study was to investigate the potential association between OBS and RA in women. METHODS: Observational surveys were performed by employing information extracted from the National Health and Nutrition Examination Survey (NHANES) for the period 2007-2018. Various statistical techniques were employed to investigate the association between OBS and RA, encompassing multivariable logistic regression analysis, subgroup analyses, smooth curve fitting, and threshold effect analysis. RESULTS: The study included 8219 female participants, including 597 patients with RA. The results showed that higher Total OBS (TOBS) significantly correlated with lower RA prevalence in the entirely modified model [odd ratio (OR) = 0.968; 95% confidence interval (CI) = 0.952 to 0.984; P = 0.0001]. Dietary OBS (DOBS) and lifestyle OBS (LOBS) also negatively correlated with RA. This association was remarkably consistent across TOBS subgroups by age, race, education level, family poverty-to-income ratio (PIR), hypertension and diabetes. Smooth curve fitting and threshold effect analysis also revealed the linear relationship between OBS and RA. CONCLUSIONS: Overall, OBS was negatively associated with RA in female. This study suggested that an antioxidant diet and lifestyle may be promising measures to prevent RA in female.


Assuntos
Antioxidantes , Artrite Reumatoide , Humanos , Feminino , Antioxidantes/metabolismo , Inquéritos Nutricionais , Estudos Transversais , Artrite Reumatoide/epidemiologia , Estresse Oxidativo
5.
Nat Commun ; 15(1): 3213, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615060

RESUMO

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.


Assuntos
Proteínas de Fase Aguda , Proteínas de Transporte , Gotículas Lipídicas , Lipopolissacarídeos , Glicoproteínas de Membrana , Homeostase , Estresse Oxidativo , Triglicerídeos
6.
Glob Chall ; 8(4): 2300258, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617028

RESUMO

To reduce the high burden of disease caused by air pollution, the World Health Organization (WHO) released new Air Quality Guidelines (AQG) on September 22, 2021. In this study, the daily fine particulate matter (PM2.5) and surface ozone (O3) data of 618 cities around the world is collected from 2019 to 2022. Based on the new AQG, the number of attainment days for daily average concentrations of PM2.5 (≤ 15 µg m-3) and O3 (≤ 100 µg m-3) is approximately 10% and 90%, respectively. China and India exhibit a decreasing trend in the number of highly polluted days (> 75 µg m-3) for PM. Every year over 68% and 27% of cities in the world are exposed to harmful PM2.5 (> 35 µg m-3) and O3 (> 100 µg m-3) pollution, respectively. Combined with the United Nations Sustainable Development Goals (SDGs), it is found that more than 35% of the world's cities face PM2.5-O3 compound pollution. Furthermore, the exposure risks in these cities (China, India, etc.) are mainly categorized as "High Risk", "Risk", and "Stabilization". In contrast, economically developed cities are mainly categorized as "High Safety", "Safety", and "Deep Stabilization." These findings indicate that global implementation of the WHO's new AQG will minimize the inequitable exposure risk from air pollution.

8.
Water Res ; 255: 121533, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38569359

RESUMO

Low-pressure mercury lamps emitting at 254 nm (UV254) are used widely for disinfection. However, subsequent exposure to visible light results in photoreactivation of treated bacteria. This study employed a krypton chloride excimer lamp emitting at 222 nm (UV222) to inactivate E. coli. UV222 and UV254 treatment had similar E. coli-inactivation kinetics. Upon subsequent irradiation with visible light, E. coli inactivated by UV254 was reactivated from 2.71-log to 4.75-log, whereas E. coli inactivated by UV222 showed negligible photoreactivation. UV222 treatment irreversibly broke DNA strands in the bacterium, whereas UV254 treatment primarily formed nucleobase dimers. Additionally, UV222 treatment caused cell membrane damage, resulting in wizened, pitted cells and permeability changes. The damage to the cell membrane was mainly due to the photolysis of proteins and lipids by UV222. Furthermore, the photolysis of proteins by UV222 destroyed enzymes, which blocked photoreactivation and dark repair. The multiple damages can be further evidenced by 4.0-61.1 times higher quantum yield in the photolysis of nucleobases and amino acids for UV222 than UV254. This study demonstrates that UV222 treatment damages multiple sites in bacteria, leading to their inactivation. Employing UV222 treatment as an alternative to UV254 could be viable for inhibiting microorganism photoreactivation in water and wastewater.

9.
Med Clin (Barc) ; 2024 Apr 02.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38570292
10.
Front Neurol ; 15: 1366307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601342

RESUMO

Objective: Acute ischemic stroke (AIS) is a heterogeneous condition. To stratify the heterogeneity, identify novel phenotypes, and develop Clinlabomics models of phenotypes that can conduct more personalized treatments for AIS. Methods: In a retrospective analysis, consecutive AIS and non-AIS inpatients were enrolled. An unsupervised k-means clustering algorithm was used to classify AIS patients into distinct novel phenotypes. Besides, the intergroup comparisons across the phenotypes were performed in clinical and laboratory data. Next, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select essential variables. In addition, Clinlabomics predictive models of phenotypes were established by a support vector machines (SVM) classifier. We used the area under curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance of the models. Results: Of the three derived phenotypes in 909 AIS patients [median age 64 (IQR: 17) years, 69% male], in phenotype 1 (N = 401), patients were relatively young and obese and had significantly elevated levels of lipids. Phenotype 2 (N = 463) was associated with abnormal ion levels. Phenotype 3 (N = 45) was characterized by the highest level of inflammation, accompanied by mild multiple-organ dysfunction. The external validation cohort prospectively collected 507 AIS patients [median age 60 (IQR: 18) years, 70% male]. Phenotype characteristics were similar in the validation cohort. After LASSO analysis, Clinlabomics models of phenotype 1 and 2 were constructed by the SVM algorithm, yielding high AUC (0.977, 95% CI: 0.961-0.993 and 0.984, 95% CI: 0.971-0.997), accuracy (0.936, 95% CI: 0.922-0.956 and 0.952, 95% CI: 0.938-0.972), sensitivity (0.984, 95% CI: 0.968-0.998 and 0.958, 95% CI: 0.939-0.984), and specificity (0.892, 95% CI: 0.874-0.926 and 0.945, 95% CI: 0.923-0.969). Conclusion: In this study, three novel phenotypes that reflected the abnormal variables of AIS patients were identified, and the Clinlabomics models of phenotypes were established, which are conducive to individualized treatments.

11.
Biochem Pharmacol ; 223: 116198, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588830

RESUMO

Agents that inhibit bromodomain and extra-terminal domain (BET) proteins have been actively tested in the clinic as potential anticancer drugs. NEDD8-activating enzyme (NAE) inhibitors, represented by MLN4924, target the only activation enzyme in the neddylation pathway that has been identified as an attractive target for cancer therapy. In this study, we focus on the combination of BET inhibitors (BETis) and NAE inhibitors (NAEis) as a cancer therapeutic strategy and investigate its underlying mechanisms to explore and expand the application scope of both types of drugs. The results showed that this combination synergistically inhibited the proliferative activity of tumor cells from different tissues. Compared to a single drug, combination therapy had a weak effect on cycle arrest but significantly enhanced cell apoptosis. Furthermore, the growth of NCI-H1975 xenografts in nude mice was significantly inhibited by the combination without obvious body weight loss. Research on the synergistic mechanism demonstrated that combination therapy significantly increased the mRNA and protein levels of the proapoptotic gene BIM. The inhibition and knockout of BIM significantly attenuated the apoptosis induced by the combination, whereas the re-expression of BIM restored the synergistic effects, indicating that BIM induction plays a critical role in mediating the enhanced apoptosis induced by the co-inhibition of BET and NAE. Together, the enhanced transcription mediated by miR-17-92 cluster inhibition and reduced degradation promoted the increase in BIM levels, resulting in a synergistic effect. Collectively, these findings highlight the need for further clinical investigation into the combination of BETi and NAEi as a promising strategy for cancer therapy.

12.
J Diabetes ; 16(4): e13549, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584275

RESUMO

AIMS: Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise-induced glycemic response. MATERIALS AND METHODS: Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). RESULTS: Combined exercise training decreased SD of sensor glucose (SDSG, exercise-pre vs exercise-post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI-quantified fat and muscle distribution, including visceral fat area (ß = -0.761, p = .001) and mid-thigh muscle area (ß = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. CONCLUSIONS: Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Glicemia , Automonitorização da Glicemia , Exercício Físico/fisiologia , Músculo Esquelético
13.
Artigo em Inglês | MEDLINE | ID: mdl-38627450

RESUMO

Hematologic toxicity frequently complicates chimeric antigen receptor (CAR) T-cell therapy, resulting in significant morbidity and mortality. In an effort to standardize reporting, the European Hematology Association (EHA) and European Society of Blood and Marrow Transplantation (EBMT) devised the immune effector cell-associated hematotoxicity (ICAHT) grading system, distinguishing between early (day 0-30) and late (after day +30) events based on neutropenia depth and duration. However, manual implementation of ICAHT grading criteria is time-consuming and susceptible to subjectivity and error. To address these challenges, we introduce a novel computational approach, utilizing the R programming language, to automate early and late ICAHT grading. Given the complexities of early ICAHT grading, we benchmarked our approach both manually and computationally in two independent cohorts totaling 1251 patients. Our computational approach offers significant implications by streamlining grading processes, reducing manual time and effort, and promoting standardization across varied clinical settings. We provide this tool to the scientific community alongside a comprehensive implementation guide, fostering its widespread adoption and enhancing reporting consistency for ICAHT.

14.
Sci Total Environ ; 927: 172171, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38575035

RESUMO

Rocky desertification is one of the most ecological problems in the karst context. Although extensive research has been conducted to explore how to restore and protect, the responses of soil fungi and archaea to rocky desertification succession remain limited. Here, four grades of rocky desertification in a karst ecosystem were selected, amplicon sequencing analysis was conducted to investigate fungal and archaeal community adaptation in response to rocky desertification succession. Our findings revealed that the diversity and community structure of fungi and archaea in soils declined with the aggravation of rocky desertification. As the rocky desertification succession intensified, microbial interactions shifted from cooperation to competition. Microbial survival strategies were K-strategist and r-strategist dominated in the early and late stages of succession, respectively. Additionally, the driving factors affecting microorganisms have shifted from vegetation diversity to soil properties as the intensification of rocky desertification. Collectively, our study highlighted that plant diversity and soil properties play important roles on soil microbiomes in fragile karst ecosystems and that environmental factors induced by human activities might still be the dominant factor exacerbating rocky desertification, which could significantly enrich our understanding of microbial ecology within karst ecosystems.

15.
Front Pharmacol ; 15: 1372139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572430

RESUMO

Background: Most preschool children are distressed during anesthesia induction. While current pharmacological methods are useful, there is a need for further optimization to an "ideal" standard. Remimazolam is an ultra-short-acting benzodiazepine, and intranasal remimazolam for pre-induction sedation may be promising. Methods: This study included 32 preschool children who underwent short and minor surgery between October 2022 and January 2023. After pretreatment with lidocaine, remimazolam was administered to both nostrils using a mucosal atomizer device. The University of Michigan Sedation Score (UMSS) was assessed for sedation 6, 9, 12, 15, and 20 min after intranasal atomization. We used Dixon's up-and-down method, and probit and isotonic regressions to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of intranasal remimazolam for pre-induction sedation. Results: Twenty-nine pediatric patients were included in the final analysis. The ED50 and ED95 of intranasal remimazolam for successful pre-induction sedation, when processed via probit analysis, were 0.65 (95% confidence interval [CI], 0.59-0.71) and 0.78 mg/kg (95% CI, 0.72-1.07), respectively. In contrast, when processed by isotonic regression, they were 0.65 (95% CI: 0.58-0.72 mg/kg) and 0.78 mg/kg (95% CI: 0.69-1.08 mg/kg), respectively. At 6 min after intranasal remimazolam treatment, 81.2% (13/16) of "positive" participants were successfully sedated with a UMSS ≧ 1. All the "positive" participants were successfully sedated within 9 min. Conclusion: Intranasal remimazolam is feasible for preschool children with a short onset time. For successful pre-induction sedation, the ED50 and ED95 of intranasal remimazolam were 0.65 and 0.78 mg/kg, respectively.

16.
PLoS One ; 19(3): e0299212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451966

RESUMO

BACKGROUND: Early-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA. METHODS: Electronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary. RESULTS: Among the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss. CONCLUSION: Early-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.


Assuntos
Dislipidemias , Síndrome Metabólica , Adulto , Humanos , Masculino , Alopecia/epidemiologia , Alopecia/genética , Estudos Transversais , Dislipidemias/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Fatores de Risco , Feminino
17.
J Agric Food Chem ; 72(11): 5805-5815, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38451212

RESUMO

Xylan is the main component of hemicellulose. Complete hydrolysis of xylan requires synergistically acting xylanases, such as ß-d-xylosidases. Salt-tolerant ß-d-xylosidases have significant application benefits, but few reports have explored the critical amino acids affecting the salt tolerance of xylosidases. Herein, the site-directed mutation was used to demonstrate that negative electrostatic potentials generated by 19 acidic residues in the loop regions of the structural surface positively correlated with the improved salt tolerance of GH39 ß-d-xylosidase JB13GH39P28. These mutants showed reduced negative potentials on structural surfaces as well as a 13-43% decrease in stability in 3.0-30.0% (w/v) NaCl. Six key residue sites, D201, D259, D297, D377, D395, and D474, were confirmed to influence both the stability and activity of GH39 ß-d-xylosidase. The activity of the GH39 ß-d-xylosidase was found promoting by SO42- and inhibiting by NO3-. Values of Km and Kcat/Km decreased aggravatedly in 30.0% (w/v) NaCl when mutation operated on residues E179 and D182 in the loop regions of the catalytic domain. Taken together, mutation on acidic residues in loop regions from catalytic and noncatalytic domains may cause the deformation of catalytic pocket and aggregation of protein particles then decrease the stability, binding affinity, and catalytic efficiency of the ß-d-xylosidase.


Assuntos
Tolerância ao Sal , Xilosidases , Xilanos/metabolismo , Cloreto de Sódio , Xilosidases/química , Especificidade por Substrato , Concentração de Íons de Hidrogênio
18.
PeerJ ; 12: e16960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436017

RESUMO

Important transformations of the pectoral girdle are related to the appearance of flight capabilities in the Dinosauria. Previous studies on this topic focused mainly on paravians yet recent data suggests flight evolved in dinosaurs several times, including at least once among non-avialan paravians. Thus, to fully explore the evolution of flight-related avian shoulder girdle characteristics, it is necessary to compare morphology more broadly. Here, we present information from pennaraptoran specimens preserving pectoral girdle elements, including all purportedly volant taxa, and extensively compare aspects of the shoulder joint. The results show that many pectoral girdle modifications appear during the evolution from basal pennaraptorans to paravians, including changes in the orientation of the coracoid body and the location of the articulation between the furcula and scapula. These modifications suggest a change in forelimb range of motion preceded the origin of flight in paravians. During the evolution of early avialans, additional flight adaptive transformations occur, such as the separation of the scapula and coracoid and reduction of the articular surface between these two bones, reduction in the angle between these two elements, and elongation of the coracoid. The diversity of coracoid morphologies and types of articulations joining the scapula-coracoid suggest that each early avialan lineage evolved these features in parallel as they independently evolved more refined flight capabilities. In early ornithothoracines, the orientation of the glenoid fossa and location of the acrocoracoid approaches the condition in extant birds, suggesting a greater range of motion in the flight stroke, which may represent the acquisition of improved powered flight capabilities, such as ground take-off. The formation of a new articulation between the coracoid and furcula in the Ornithuromorpha is the last step in the formation of an osseous triosseal canal, which may indicate the complete acquisition of the modern flight apparatus. These morphological transitions equipped birds with a greater range of motion, increased and more efficient muscular output and while at the same time transmitting the increased pressure being generated by ever more powerful flapping movements in such a way as to protect the organs. The driving factors and functional adaptations of many of these transitional morphologies are as yet unclear although ontogenetic transitions in forelimb function observed in extant birds provide an excellent framework through which we can explore the behavior of Mesozoic pennaraptorans.


Assuntos
Dinossauros , Articulação do Ombro , Animais , Extremidade Superior , Membro Anterior , Aves , Escápula
19.
World J Surg ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520680

RESUMO

PURPOSE: Ventral hernia (VH) is a common surgical disease. Previous studies suggested that obesity is an important risk factor for VH. However, the causal relationship between fat distribution and the risk of VH is still unclear. This study used Mendelian randomization (MR) to evaluate their causal relationship. METHODS: We used the body mass index (BMI), body fat percentage, and body fat mass to represent general obesity and utilized the volume of abdominal subcutaneous adiposity tissue, visceral adiposity tissue, waist circumference, hip circumference, and waist-to-hip ratio to represent abdominal adiposity. The data were extracted from the large-scale genome-wide association study of European ancestry. We used two-sample MR to infer causality, using multivariate MR to correct the effects of confounding factors. RESULTS: Increased BMI, body fat percentage, body fat mass, visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or waist-to-hip ratio, were causally associated with a higher risk of VH. The results of multivariate MR suggested that body fat percentage was causally associated with a higher risk of VH after adjusting for body mass index, diabetes, and smoking. CONCLUSION: General obesity, increased visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or the waist-to-hip ratio were causally associated with a higher risk of VH. These findings provided a deeper understanding of the role that the distribution of adiposity plays in the mechanism of VH.

20.
EMBO J ; 43(8): 1445-1483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499786

RESUMO

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.


Assuntos
Apoferritinas , Linfócitos T Reguladores , Humanos , Animais , Camundongos , Apoferritinas/genética , Apoferritinas/metabolismo , Linhagem da Célula/genética , Citosina/metabolismo , Fatores de Transcrição Forkhead , Ferro/metabolismo
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