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1.
Nutrients ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732537

RESUMO

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.


Assuntos
Disruptores Endócrinos , Ácidos Ftálicos , Sono , Deficiência de Vitamina D , Vitamina D , Humanos , Disruptores Endócrinos/efeitos adversos , Deficiência de Vitamina D/epidemiologia , Feminino , Masculino , Estados Unidos/epidemiologia , Adulto , Ácidos Ftálicos/efeitos adversos , Pessoa de Meia-Idade , Sono/efeitos dos fármacos , Vitamina D/sangue , Fenóis/efeitos adversos , Exposição Ambiental/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Inquéritos Nutricionais , Triclosan/efeitos adversos , Idoso , Adulto Jovem
2.
Heliyon ; 10(10): e30860, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38774321

RESUMO

Background: Accurately predicting the survival rate of submandibular gland cancer (SGC) is of significant importance for guiding treatment decision-making and improving patient outcomes. This study was aimed to identify the independent prognostic factors of overall survival (OS) in SGC patients, and develop novel prediction models to aid clinicians in predicting the survival probability. Materials and methods: Patients diagnosed with primary SGC after the year 2010 were extracted from SEER database and then randomly allocated into training and test samples in a 7:3 ratio. Uni- and multi-variable COX analyses were employed using the training sample to ascertain independent prognostic factors for OS. Subsequently, graphic and online dynamic nomograms were established basing on the independent prognostic factors. We utilized C-index, calibration curve, receiver operating characteristic (ROC) curve, and area under ROC curve (AUC) value to evaluate the discrimination capacity and the consistency between predicted and actual survival. Results: A total of 527 SGC patients were included (369 assigned to training group and 158 assigned to test group). The multivariable COX analysis showed that age, sex, marital status, tumor histology, summary stage, metastases to bone, and tumor size were independently associated with OS. Novel graphical and online dynamic (URL: https://yangxg1209.shinyapps.io/overall_survival_submandibular_gland_tumor/) nomograms were established. The C-indices (training: 0.77, 95%CI 0.71-0.84; test: 0.77, 95%CI 0.68-0.85) indicate favorable discrimination ability of the model, and the calibration curves demonstrated favorable consistency between the predicted and actual survival rates. Conclusions: Our study identified the independent prognostic factors influencing OS in patients with SGC, and successfully established and validated novel nomograms, which provide accurate prediction of survival rates and allows for personalized risk assessment.

3.
Behav Brain Res ; 469: 115021, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692358

RESUMO

This study aims to investigate the brain networks engaged in the comprehension of indirect language, as well as the individual difference in this capacity. Specially, we aim to determine whether the difference is solely influenced by the difference in individuals' default network (DN)/language network or whether it also relies on the networks associated with processing of complex cognitive tasks, particularly the multiple demand network (MDN). Conversational indirectness scale (CIS) scores in the interpretation dimension were used as a behavioral indicator of the indirect comprehension tendency. Reading time difference between indirect replies and direct replies collected through a self-paced reading experiment was deemed as a behavioral indicator of comprehension speed of indirect replies comprehension. The two behavioral indicators were combined with resting-state functional magnetic resonance imaging (rs-fMRI). The behaviour-rfMRI analysis showed that ALFF value of right SPL and the functional connectivity (FC) between the right SPL and right IPL/SMA/ITG/Precuneus/bilateral IFG were positively correlated with the interpretation dimension of CIS scores. In addition, the ALFF value of right fusiform gyrus, the FC between the right fusiform gyrus and right precuneus, and the FCs between right SPL and right IPL/Precuneus/IFG were negatively correlated with indirect replies comprehension speed. Overlapping of these regions with large-scale brain network revealed that the right SPL was mainly located in the MDN, and the right fusiform gyrus was mainly located in the language network. Additionally, the areas showing functional connectivity with these regions were primarily located in the MDN, with a smaller subset located in the DN. Our findings suggest that the ability of individuals to actively and rapidly acquire indirect meaning relies not only on the support of the DN and the language network, but also requires collective support from the MDN.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38755082

RESUMO

BACKGROUND AND AIMS: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. METHODS AND RESULTS: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. CONCLUSION: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38773021

RESUMO

The objective of this study was to investigate the impact of music training on the processing of temporal order in Mandarin sentence reading using event-related potentials (ERPs). Two-clause sentences with temporal connectives ("before" or "after") were presented to both musicians and non-musicians. Additionally, a verbal N-back task was utilized to evaluate the participants' working memory capacities. The findings revealed that musicians, but not nonmusicians, demonstrated a more negative amplitude in the second clauses of "before" sentences compared with "after" sentences. In the N-back task, musicians exhibited faster reaction times than nonmusicians in the two-back condition. Furthermore, a correlation was observed between the ERP amplitude differences (before vs. after) and reaction time differences in the N-back task (0-back vs. 2-back) among musicians. These findings suggested that music training enhances the depth of temporal order processing, potentially mediated by improvements in working memory capacity.

6.
Adv Sci (Weinh) ; : e2401009, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751156

RESUMO

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

7.
Psychol Res Behav Manag ; 17: 1573-1585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617578

RESUMO

Background: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD. Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively. Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p<0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p<0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047). Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.

8.
World J Diabetes ; 15(4): 697-711, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38680694

RESUMO

BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [ß 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The ß (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

9.
Front Microbiol ; 15: 1379484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680920

RESUMO

Purpose: This study aims to investigate the effects of frozen storage on the stability of traditional dough starters in China. Methods: The microbial community structure and abundance of related metabolic genes in different fermented sourdough prepared by Jiaozi (JZ) and Laomian (LM) starters before and after frozen storage at -20°C for half a year were analyzed using the shotgun metagenomic sequencing method, and differences in characteristics of texture in steamed bread were also compared by formal methods. Results: The fermentation ability (FA) and metabolic activities of yeast in the JZH sourdough (started by JZ which was stored at -20°C for half a year) were better than those of LMH sourdough (started by LM which was stored at -20°C for half a year). The dominant genera of Acetobacter were found to be increased in the JZH0 sourdough (started by JZH and fermented for 0 h) and those of Lactobacillus were found to be decreased. Lactobacillus (98.72%), Pediococcus (0.37%), Saccharomyces (0.27%), and Acetobacter (0.01%), were dominant in sourdough LMH0 (started by LMH and fermented for 0 h). The abundances of "oxidative phosphorylation-related enzymes" and the "biosynthesis of glutamate"-related enzymes and genes related to "biosynthesis of glutamate" and "unsaturated fatty acid" were higher in JZH0 than in the JZ0 sourdough (started by JZ without being frozen and fermented for 0 h). The good FA of yeast, the acid production capacity of bacteria in the sourdough, and the quality of the JZH steamed bread (made by the JZH starter) indicated the better freezing tolerance of the microorganisms in JZ than in LM. Conclusion: The conclusion of this study suggests the better application potential of the JZ as the fermentation starter in actual production.

10.
Molecules ; 29(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38675651

RESUMO

Outer membrane vesicles (OMVs) are attractive for biomedical applications based on their intrinsic properties in relation to bacteria and vesicles. However, their widespread use is hampered by low yields and purities. In this study, EVscore47 multifunctional chromatography microspheres were synthesized and used to efficiently isolate functional OMVs from Escherichia coli. Through this technology, OMV loss can be kept to a minimum, and OMVs can be harvested using EVscore47 at 11-fold higher yields and ~13-fold higher purity than those achieved by means of ultracentrifugation. Based on the results presented here, we propose a novel EVscore47-based isolation of OMVs that is fast and scalable.


Assuntos
Escherichia coli , Vesículas Extracelulares , Microesferas , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Membrana Externa Bacteriana/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Ultracentrifugação , Cromatografia/métodos
11.
Theor Appl Genet ; 137(5): 102, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607439

RESUMO

KEY MESSAGE: A total of 389 and 344 QTLs were identified by GWAS and QTL mapping explaining accumulatively 32.2-65.0% and 23.7-63.4% of phenotypic variation for 14 shoot-borne root traits using more than 1300 individuals across multiple field trails. Efficient nutrient and water acquisition from soils depends on the root system architecture (RSA). However, the genetic determinants underlying RSA in maize remain largely unexplored. In this study, we conducted a comprehensive genetic analysis for 14 shoot-borne root traits using 513 inbred lines and 800 individuals from four recombinant inbred line (RIL) populations at the mature stage across multiple field trails. Our analysis revealed substantial phenotypic variation for these 14 root traits, with a total of 389 and 344 QTLs identified through genome-wide association analysis (GWAS) and linkage analysis, respectively. These QTLs collectively explained 32.2-65.0% and 23.7-63.4% of the trait variation within each population. Several a priori candidate genes involved in auxin and cytokinin signaling pathways, such as IAA26, ARF2, LBD37 and CKX3, were found to co-localize with these loci. In addition, a total of 69 transcription factors (TFs) from 27 TF families (MYB, NAC, bZIP, bHLH and WRKY) were found for shoot-borne root traits. A total of 19 genes including PIN3, LBD15, IAA32, IAA38 and ARR12 and 19 GWAS signals were overlapped with selective sweeps. Further, significant additive effects were found for root traits, and pyramiding the favorable alleles could enhance maize root development. These findings could contribute to understand the genetic basis of root development and evolution, and provided an important genetic resource for the genetic improvement of root traits in maize.


Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Humanos , Zea mays/genética , Genômica , Mapeamento Cromossômico , Alelos
12.
Diabetes Metab Res Rev ; 40(4): e3802, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38634501

RESUMO

AIMS: To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade. MATERIALS AND METHODS: We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden. RESULTS: In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade. CONCLUSIONS: The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.


Assuntos
Glicemia , Carga Global da Doença , Masculino , Feminino , Humanos , Idoso , Teorema de Bayes , Saúde Global , Cegueira , Jejum , Anos de Vida Ajustados por Qualidade de Vida
13.
Adv Healthc Mater ; : e2304485, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567748

RESUMO

Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy.

15.
Blood Adv ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551808

RESUMO

Phenotype D-- is associated with severe hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. It is typically caused by defective RHCE genes. In this study, we identified a D-- phenotype proband and verified RH phenotypes of other six family members. However, inconsistent results between the phenotypic analysis and Sanger sequencing revealed intact RHCE exons with no mutations in the D-- proband, but the protein was not expressed. Subsequent Oxford Nanopore Technologies whole-genome sequencing of the proband revealed an inversion with ambiguous breakpoints in the intron 2 and intron 7 and copy number variation loss in the RHCE gene region. Given that the RHCE gene is highly homologous to the RHD gene, we conducted a comprehensive analysis using Pacific Biosciences long-read target sequencing, Bionano optical genome mapping, and targeted next-generation sequencing. Our findings revealed that the proband had two novel recombinant RHCE haplotypes, RHCE*Ce(1-2)-D(3-10) and RHCE*Ce(1-2)-D(3-10)-Ce(10-8)-Ce(3-10), with clear-cut breakpoints identified. Furthermore, the RH haplotypes of the family members were identified and verified. In summary, we made a novel discovery of hereditary large inversion and recombination events occurring between the RHD and RHCE genes, leading to lack of RhCE expression. This highlights the advantages of using integrated genetic analyses and also provides new insights into RH genotyping.

16.
Plant Biotechnol J ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548388

RESUMO

Carotenoids are indispensable to plants and critical components of the human diet. The carotenoid metabolic pathway is conserved across plant species, but our understanding of the genetic basis of carotenoid variation remains limited for the seeds of most cereal crops. To address this issue, we systematically performed linkage and association mapping for eight carotenoid traits using six recombinant inbred line (RIL) populations. Single linkage mapping (SLM) and joint linkage mapping (JLM) identified 77 unique additive QTLs and 104 pairs of epistatic QTLs. Among these QTLs, we identified 22 overlapping hotspots of additive and epistatic loci, highlighting the important contributions of some QTLs to carotenoid levels through additive or epistatic mechanisms. A genome-wide association study based on all RILs detected 244 candidate genes significantly associated with carotenoid traits, 23 of which were annotated as carotenoid pathway genes. Effect comparisons suggested that a small number of loci linked to pathway genes have substantial effects on carotenoid variation in our tested populations, but many loci not associated with pathway genes also make important contributions to carotenoid variation. We identified ZmPTOX as the causal gene for a QTL hotspot (Q10/JLM10/GWAS019); this gene encodes a putative plastid terminal oxidase that produces plastoquinone-9 used by two enzymes in the carotenoid pathway. Natural variants in the promoter and second exon of ZmPTOX were found to alter carotenoid levels. This comprehensive assessment of the genetic mechanisms underlying carotenoid variation establishes a foundation for rewiring carotenoid metabolism and accumulation for efficient carotenoid biofortification.

17.
Pharmaceutics ; 16(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38543217

RESUMO

Most antiviral and anticancer nucleosides are prodrugs that require stepwise phosphorylation to their triphosphate nucleotide form for biological activity. Monophosphorylation may be rate-limiting, and the nucleotides may be unstable and poorly internalized by target cells. Effective targeting and delivery systems for nucleoside drugs, including oligonucleotides used in molecular therapeutics, could augment their efficacy. The development of a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor (ASGPr) is now reported. In this work, the polycationic, polygalactosyl drug delivery carrier heptakis[6-amino-6-deoxy-2-O-(3-(1-thio-ß-D-galactopyranosyl)-propyl)]-ß-cyclodextrin hepta-acetate salt (GCyDAc), potentially a bifunctional carrier of (poly)nucleotides, was modeled by molecular docking in silico as an ASGPr-ligand, then synthesized for testing. The antivirals arabinosyl adenine (araA, vidarabine, an early generation antiviral nucleoside), arabinosyl adenine 5'-monophosphate (araAMP), and 12-mer-araAMP (p-araAMP) were selected for individual formulation with GCyDAc to develop this concept. Experimentally, beta cyclodextrin was decorated with seven protonated amino substituents on the primary face, and seven thiogalactose residues on its secondary face. AraA, araAMP, and p-araAMP were individually complexed with GCyDAc and complex formation for each drug was confirmed by differential scanning calorimetry (DSC). Finally, the free drugs and their GCyDAc complexes were evaluated for antiviral activity using ASGPr-expressing HepAD38 cells in cell culture. In this model, araA, araAMP, and p-araAMP showed relative antiviral potencies of 1.0, 1.1, and 1.2, respectively. In comparison, GCyDAc-complexes of araA, araAMP, and p-araAMP were 2.5, 1.3, and 1.2 times more effective than non-complexed araA in suppressing viral DNA production. The antiviral potencies of these complexes were minimally supportive of the hypothesis that ASGPr-targeted, CyD-based charge-association complexation of nucleosides and nucleotides could effectively enhance antiviral efficacy. GCyDAc was non-toxic to mammalian cells in cell culture, as determined using the MTS proliferation assay.

18.
Medicine (Baltimore) ; 103(11): e37540, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489682

RESUMO

This study is an observation of the early screening and treatment effect of infant developmental dysplasia of the hip (DDH) in an area in China. From January 2016 to December 2017, we selected infants and toddlers with high-risk factors for DDH, such as asymmetric gluteal folds, unequal length of lower limbs, and limited hip joint abduction, who visited the Department of Child Health Care and the Outpatient Clinic of Pediatric Orthopedics at the Affiliated Hospital of Zunyi Medical University. In total, 1485 cases were divided into age groups, examined using Graf ultrasound and X-ray, and the results were analyzed. Meanwhile, early interventions were actively adopted for cases with abnormalities during the screening. The detection rates of DDH were 24.0%, 2.8%, 9.3%, and 12.2% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. Early and individualized corrective conservative treatment was considered for children with abnormalities, and the cure rates were 87.0%, 65.7%, 41.0%, and 16.7% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. There was a statistically significant difference in the detection and cure rates of DDH in infants and toddlers of different ages (P < .01).


Assuntos
Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Lactente , Humanos , Pré-Escolar , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/epidemiologia , Radiografia , Extremidade Inferior , Ultrassonografia/efeitos adversos
19.
Int J Surg ; 110(4): 2092-2103, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38348839

RESUMO

BACKGROUND: To assess the burden and change in incidence, death, and disability-adjusted life years (DALYs) for all-cause-specific injuries among children and adolescents in 204 countries and territories between 1990 and 2019. MATERIALS AND METHODS: Data were extracted from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019). Global, regional, and country-level age-standardized rate (per 100 000) of incidence (ASRI), mortality (ASRM), and DALYs (ASRD) with 95% uncertainty interval (95% UI) of injuries were estimated by age, sex, socio-demographic index (SDI), and all-cause-specific injuries from 1990 to 2019. RESULTS: Overall, the ASRI, ASRM, and ASRD of injury were 9006.18 (95% UI: 7459.74-10 918.04), 23.04 (20.00-26.50), and 2020.19 (1759.47-2318.64) among children and adolescents worldwide in 2019, respectively. All the above indicators showed a downward trend from 1990 to 2019. In level 2 cause of injury, both the global transport injury and unintentional injury declined during the study years, while self-harm and interpersonal violence-related injury showed an increasing trend. High SDI regions had higher ASRI of injuries, but low SDI regions had higher ASRM and ASRD of injuries globally in 2019. Males had a higher burden of injuries than those in females. The ASRI of injuries is higher in adolescents aged 15-19 years, whereas the mortality and DALYs rate are higher among children under 5 years old. Moreover, adolescents aged 15-19 years and individuals living in Central Asia, Middle East, and Africa had higher ASRI, ASRM, and ASRD of injuries owing to self-harm and interpersonal violence. Generally, falls and road traffic injuries are the leading cause of injury among the population aged 0-19 years worldwide, but self-harm, interpersonal violence, and conflict and terrorism are also leading types of injuries in some regions, particularly in Low-Income Countries and Middle-Income Countries. CONCLUSIONS: Injury remains a major global public health problem among children and adolescents, although its burden at the worldwide level showed a decreasing trend from 1990 to 2019. Of concern, the burden of injuries caused by transport injuries, and unintentional injuries has shown a downward trend in most countries, while the burden caused by self-harm and interpersonal violence has shown an upward trend in most countries. These findings suggest that more targeted and specific strategies to prevent the burden of injuries should be reoriented, and our study provides important findings for decision-makers and healthcare providers to reduce injury burden among children and adolescents.


Assuntos
Carga Global da Doença , Saúde Global , Ferimentos e Lesões , Humanos , Adolescente , Criança , Masculino , Feminino , Ferimentos e Lesões/epidemiologia , Estudos Prospectivos , Pré-Escolar , Lactente , Saúde Global/estatística & dados numéricos , Incidência , Anos de Vida Ajustados por Deficiência , Recém-Nascido , Anos de Vida Ajustados por Qualidade de Vida
20.
Medicine (Baltimore) ; 103(7): e35832, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363920

RESUMO

BACKGROUND: The mechanism of action of fire acupuncture and Chinese medicine in psoriasis is unclear. In this paper, the efficacy of the 2 therapies was compared through a comprehensive analysis of their recurrence rates for clinical reference. METHODS: In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM data from the establishment of the databases to May 2023. The study proposed to use randomized controlled trial research methods, excluding published literature, unpublished literature, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies. Data were processed using STATA 15.1 software. RESULTS: Our group previous study found that the clinical efficacy of the fire-acupuncture group was significantly improved compared to that of Chinese herbal medicine alone (RR = 1.20, 95% CI: 1.13-1.27). Also, there were significant reductions in Psoriasis Area and Severity Index (PASI) score (SMD = -1.04,95% CI: -1.48 to -0.60), area of skin damage (SMD = -0.40,95% CI: -0.75 to -0.04), and pruritus (SMD = -1.04,95% CI: -1.32 to -0.76). Our previous study found that Dermatology Life Quality Index (DLQI) was significantly lower in the fire acupuncture group compared to herbal medicine alone (SMD = -1.61,95% CI: -3.08 to -0.15). The combined analysis found that the recurrence rate was significantly lower in the fire-acupuncture group compared to herbal medicine alone (RR = 0.21,95% CI:0.07-0.60). CONCLUSION: Fire needle can improve the efficacy of TCM in the treatment of psoriasis, including the area, severity and itching of skin lesions, and reduce the recurrence rate, which is worthy of clinical promotion.


Assuntos
Terapia por Acupuntura , Psoríase , Animais , Medicina Tradicional Chinesa , Psoríase/tratamento farmacológico , Prurido , Extratos Vegetais/uso terapêutico
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