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1.
Midwifery ; 133: 103994, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608543

RESUMO

BACKGROUND: Women undergoing caesarean section (CS) experience difficulties when preparing for discharge, and readiness for hospital discharge (RHD) may depend on individual characteristics. OBJECTIVE: To explore the status of RHD in women with CS, identify the latent classes of RHD, and analyse predictors from a bio-psycho-social perspective. METHODS: A sample of 410 women with CS completed the following questionnaires on demographic and obstetric characteristics: Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF), Parents' Postnatal Sense of Security (PPSS), Quality of Discharge Teaching Scale (OB-QDTS), and Postpartum Support Questionnaire (PSQ). Latent profile analysis was used to identify the latent classes of RHD. Multiple logistic regression analysis was used to analyse the predictors. RESULTS: In total, 96.6 % of women with CS reported discharge ready, and the score of RHDS-NMF was 136.09 ± 25.59. Three latent classes were identified as Low RHD (16.1 %), Moderate RHD (41.7 %), and High RHD (42.2 %). Primiparas (OR = 2.867 / 1.773; P = 0.012 / 0.033), emergency CS (OR = 3.134 / 2.470; P = 0.006 / 0.002), lower levels of PPSS (OR = 0.909 / 0.942; P = 0.009 / 0.013) and OB-ODTS (OR = 0.948 / 0.975; P < 0.001) were associated with Moderate and Low RHD. Lower PSQ predicted a higher probability of Low RHD (OR = 0.955; P = 0.038). CONCLUSIONS: The perception of RHD by women in the study was inaccurate, with more than half not being classified as High RHD. Healthcare professionals can anticipate interventions for maternal well-being based on the characteristics of the different RHD classes.

2.
Aging (Albany NY) ; 162024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38643465

RESUMO

Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that the expression of thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting that the alteration of thyroidal elements, especially the decreased TRα, might attenuate local THs action thus to cause the degeneration of SM with aging, while the underlying mechanism remains to be further explored. In this study, decreased expression of myogenic regulators Myf5, MyoD1, mitophagy markers Pink1, LC3II/I, p62, as well as mitochondrial dynamic factors Mfn1 and Opa1, accompanied by increased reactive oxygen species (ROS), showed concomitant changes with reduced TRα expression in aged mice. Further TRα loss- and gain-of-function studies in C2C12 revealed that silencing of TRα not only down-regulated the expression of above-mentioned myogenic regulators, mitophagy markers and mitochondrial dynamic factors, but also led to a significant decrease in mitochondrial activity and maximum respiratory capacity, as well as more mitochondrial ROS and damaged mitochondria. Notedly, overexpression of TRα could up-regulate the expression of those myogenic regulators, mitophagy markers and mitochondrial dynamic factors, meanwhile also led to an increase in mitochondrial activity and number. These results confirmed that TRα could concertedly regulate mitochondrial dynamics, autophagy, and activity, and myogenic regulators rhythmically altered with TRα expression. Summarily, these results suggested that the decline of TRα might cause the degeneration of SM with aging by regulating mitochondrial dynamics, mitophagy and myogenesis.

3.
Dalton Trans ; 53(13): 5917-5921, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38456197

RESUMO

A new magnesium-based metal-organic framework with unprecedented short-chain secondary building units and ultra-micropore channels approaching the kinetic diameters of Xe is fabricated by decorating methyl groups on ligands. Due to the contracted pores, this MOF exhibits very high selectivity values for Xe/Kr, which ranks it among the top porous absorbents.

4.
BMC Pregnancy Childbirth ; 24(1): 167, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408952

RESUMO

BACKGROUND: The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. METHODS: A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-phthalates exposure interactions. RESULTS: There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28-2.37; dominant: aOR = 1.86, 95% CI:1.25-2.78; recessive: aOR = 2.50, 95% CI: 1.26-4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54-121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. CONCLUSIONS: The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.


Assuntos
Cardiopatias Congênitas , Exposição Materna , Ácidos Ftálicos , Feminino , Humanos , Exposição Materna/efeitos adversos , Estudos de Casos e Controles , Espectrometria de Massas em Tandem , Estudos Prospectivos , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
6.
J Clin Transl Hepatol ; 12(1): 79-90, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38250462

RESUMO

The liver is the largest glandular organ in the body and has a unique distribution of cells and biomolecules. However, the treatment outcome of end-stage liver disease is extremely poor. Single-cell sequencing is a new advanced and powerful technique for identifying rare cell populations and biomolecules by analyzing the characteristics of gene expression between individual cells. These cells and biomolecules might be used as potential targets for immunotherapy of liver diseases and contribute to the development of precise individualized treatment. Compared to whole-tissue RNA sequencing, single-cell RNA sequencing (scRNA-seq) or other single-cell histological techniques have solved the problem of cell population heterogeneity and characterize molecular changes associated with liver diseases with higher accuracy and resolution. In this review, we comprehensively summarized single-cell approaches including transcriptomic, spatial transcriptomic, immunomic, proteomic, epigenomic, and multiomic technologies, and described their application in liver physiology and pathology. We also discussed advanced techniques and recent studies in the field of single-cell; our review might provide new insights into the pathophysiological mechanisms of the liver to achieve precise and individualized treatment of liver diseases.

7.
Aging (Albany NY) ; 16(1): 493-517, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38194709

RESUMO

BACKGROUND: Sarcomas are a type of highly heterogeneous malignant tumors originating from mesenchymal tissues. Necroptosis is intricately connected to the oncogenesis and progression of tumors. The main goal of this research is to assess the prognostic value of necroptosis-related lncRNAs (NRlncRNAs) in sarcomas and to develop a risk model based on NRlncRNAs to evaluate prognostic and immune status of the sarcomas. METHODS: We screened NRlncRNAs using the gene co-expression network, developed a prognostic risk model of sarcomas, and then verified the model. Following that, various bioinformatics analysis algorithms were employed to analyze the distinct characteristics of patients of the risk model. Furthermore, the function and regulatory mechanism of NRlncRNA SNHG6 in sarcomas were investigated through osteosarcoma cell experiments, such as qRT-PCR, Western blot, CCK-8, clone formation, and transwell assay. RESULTS: We successfully developed a NRlncRNAs-related prognostic risk model and screened 5 prognosis-related NRlncRNAs, with SNGH6 being the most significant for prognosis of patients. According to results, the significant differences exist in prognosis, clinical characteristics, and tumor immune status among patients of the risk model. The experiments of osteosarcoma cells demonstrated that NRlncRNA SNHG6 knockdown significantly attenuated the cells' proliferation, migration, and invasion. qRT-PCR and WB results showed that SNHG6 regulated AXL and AKT signaling. CONCLUSIONS: We have developed an innovative investigation on NRlncRNAs, which can serve as a reference for diagnosis, therapy, and prognosis of sarcomas. Additionally, we demonstrated that NRlncRNA SNHG6 regulated AXL and AKT signaling in osteosarcoma cells and the proliferation, migration, and invasion of tumor cells.


Assuntos
Neoplasias Ósseas , Osteossarcoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/genética , Necroptose/genética , Prognóstico , Osteossarcoma/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica
8.
Rev Esp Enferm Dig ; 116(1): 53-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37073713

RESUMO

A 60-year-old man was admitted to our hospital for routine postoperative review of colon cancer. He underwent a colonoscopy, which showed a bridge-like polyp located 13 cm from the anal verge, with the base of the polyp located 1.5 cm above the anastomosis and the head of it located on the anastomosis and fusion growth with the anastomosiz. The patient accepted ESD to remove the lesion. During the ESD procedure, the basal of the polyp was incised using an insulated-tip knife, when the polyp tip located at the anastomosis was gradually dissected with a hook knife, severe fibrosis and three staples was found in the submucosal. We carefully separated the scar tissue and pulled out staples with hook knife in electrocision mode. Finally, we removed the lesion completely.


Assuntos
Ressecção Endoscópica de Mucosa , Pólipos , Masculino , Humanos , Pessoa de Meia-Idade , Colonoscopia/métodos , Anastomose Cirúrgica , Canal Anal
9.
J Oral Maxillofac Surg ; 82(2): 152-158, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37926429

RESUMO

BACKGROUND: Video-stylet-guided nasotracheal intubation (NTI) is an effective technique for airway management. However, the impact of the bend angle on the success rate of intubation remains unclear. PURPOSE: Does increasing the bend angle of a stylet to 90° increase NTI success rate?. STUDY DESIGN, SETTING, SAMPLE: This prospective randomized controlled trial was conducted in the operating room of a population-based hospital. Adult patients requiring NTI were recruited. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable is the choice of stylet bend angle (90° vs 70° bend) in NTI. MAIN OUTCOME VARIABLE(S): The primary outcome variables were success rates of NTI, defined as the proportion of successful intubation cases to total cases. COVARIATES: Demographics, intubation time, the distance from the thyroid prominence to the nostril, additional maneuvers applied during intubation, and cases of epistaxis were recorded. ANALYSES: The student's t-test was used to compare continuous variables between groups. Ordinal data (intubation attempts, head extension, and epistaxis) were analyzed using the Wilcoxon rank-sum test. As appropriate, frequency (external pharyngeal pressure) was analyzed using the χ2 test or Fisher's exact test. A P value of <.05 was considered statistically significant. RESULTS: Of the 103 subjects assessed for eligibility, 98 were enrolled in the study. The mean age (27.0 ± 6.9 years vs 27.0 ± 4.1 years, P = .972) and sex differences (male/female: 9/40 vs 7/42, P = .136) were comparable between groups. The overall success rate in the 70° group was significantly lower than that in the 90° group (91.8 vs 100%, P < .001). The intubation time in the 70° group was significantly longer than that in the 90° group (43.2 ± 15.8 s vs 33.7 ± 7.3 s, P < .001). CONCLUSIONS AND RELEVANCE: A 90° bend angle of the stylet significantly improves the likelihood of successful NTI.


Assuntos
Epistaxe , Cavidade Nasal , Adulto , Humanos , Masculino , Feminino , Adulto Jovem , Estudos Prospectivos , Intubação Intratraqueal/métodos
10.
Rev. esp. enferm. dig ; 116(3): 168-169, 2024. ilus
Artigo em Inglês | IBECS | ID: ibc-231483

RESUMO

A 47-year-old man with a history of ESMC resection of the left chest wall seven years ago was admitted to our hospital due to mid-upper abdominal pain and jaundice for more than 10 days. Laboratory tests showed elevated direct bilirubin, alanine aminotransferase, gamma-glutamyltranspeptidase, and alkaline phosphatase. Computed tomography (CT) of the abdomen revealed soft tissue mass in the head and body of the pancreas with irregularly shaped calcifications, and an enhanced scan showed heterogeneous enhancement. Combined with the patient's past medical history, the possibility of pancreatic metastasis of ESMC was considered. After anti-inflammatory, hepatoprotective, and cholagogical treatment jaundice improved, and ultrasound endoscopy-guided fine-needle aspiration (EUS-FNA) was performed to clarify the nature of the mass, which showed a 4.1*4.2 cm mixed echogenic area with internal calcification in the head of the pancreas. Aspiration pathology showed proliferation of short spindle and round cells into nests, the immunohistochemistry stain showed CD99 (+); CD34, CD117, Dog-1, and S-100 were negative. Pancreatic metastasis of ESMC was diagnosed. Four months later, endoscopic biliary metal stent drainage (EMBD) was performed when the patient developed obstructive jaundice again due to lesion progression. PET/CT at a 2-year follow-up showed multiple high-density calcifications and abnormally increased FDG metabolism throughout the body. (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/terapia , Condrossarcoma Mesenquimal , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas
12.
Sci Total Environ ; 917: 169306, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38103614

RESUMO

Microcystins (MCs) are the most common cyanobacterial toxins. Epidemiological investigation showed that exposure to MCs can cause gastro-intestinal symptoms, gastroenteritis and gastric cancer. MCs can also accumulate in and cause histopathological damage to stomach. However, the exact mechanisms by which MCs cause gastric injury were unclear. In this study, Wistar rats were administrated 50, 75 or 100 µg microcystin-LR (MC-LR)/kg, body mass (bm) via tail vein, and histopathology, response of anti-oxidant system and the proteome of gastric tissues at 24 h after exposure were studied. Bleeding of fore-stomach and gastric corpus, inflammation and necrosis in gastric corpus and exfoliation of mucosal epithelial cells in gastric antrum were observed following acute MC-LR exposure. Compared with controls, activities of superoxide dismutase (SOD) were significantly greater in gastric tissues of exposed rats, while activities of catalase (CAT) were less in rats administrated 50 µg MC-LR/kg, bm, and concentrations of glutathione (GSH) and malondialdehyde (MDA) were greater in rats administrated 75 or 100 µg MC-LR/kg, bm. These results indicated that MC-LR could disrupt the anti-oxidant system and cause oxidative stress. The proteomic results revealed that MC-LR could affect expressions of proteins related to cytoskeleton, immune system, gastric functions, and some signaling pathways, including platelet activation, complement and coagulation cascades, and ferroptosis. Quantitative real-time PCR (qRT-PCR) analysis showed that transcriptions of genes for ferroptosis and gastric function were altered, which confirmed results of proteomics. Overall, this study illustrated that MC-LR could induce gastric dysfunction, and ferroptosis might be involved in MC-LR-induced gastric injury. This study provided novel insights into mechanisms of digestive diseases induced by MCs.


Assuntos
Antioxidantes , Toxinas Marinhas , Microcistinas , Ratos , Animais , Antioxidantes/metabolismo , Microcistinas/toxicidade , Microcistinas/metabolismo , Proteômica , Fígado/metabolismo , Ratos Wistar , Estresse Oxidativo , Glutationa/metabolismo , Estômago
13.
World J Pediatr ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070097

RESUMO

BACKGROUND: The prevalence of congenital diaphragmatic hernia (CDH) varies across countries, with limited information available on its epidemiology in China. Our study aimed to investigate the prevalence, time trends, and perinatal outcomes of CDH in China, as well as its associated malformations and potential associations with maternal and infant characteristics. METHODS: This study included all birth and CDH cases from the Chinese Birth Defects Monitoring Network between 2007 and 2019, with CDH cases classified as either isolated or associated. We employed the joinpoint regression model to calculate the trends of prevalence and the annual percent change, with Poisson regression used for adjusted prevalence rate ratios. A P value ≤ 0.05 was considered statistically significant. RESULTS: A total of 4397 CDH cases were identified among 24,158,029 births in the study period, yielding prevalence rates of 1.82, 1.13 and 0.69 per 10,000 for overall, isolated, and associated CDH, respectively. The prevalence of each type of CDH increased over time. The prevalence of overall CDH varied significantly by infant sex (male vs. female, 1.91/10,000 vs. 1.63/10,000), maternal residence (urban vs. rural, 2.13/10,000 vs. 1.45/10,000), maternal age (< 20 years, 1.31/10,000; 20-24 years, 1.63/10,000; 25-29 years, 1.80/10,000; 30-34 years, 1.87/10,000; ≥ 35 years, 2.22/10,000), and geographic region (central, 1.64/10,000; east, 2.45/10,000; west, 1.37/10,000). Cardiovascular anomalies were the most common malformations associated with CDH. Infants with associated CDH had a higher risk of premature birth and perinatal death than those with isolated CDH. CONCLUSION: The increasing prevalence and high perinatal mortality rate of CDH highlight the need for further etiological, epidemiological, and clinical studies among the Chinese population. Video Abstract.

14.
FASEB J ; 37(12): e23270, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37994683

RESUMO

Rapid advances in high-quality sequencing and bioinformatics have invalidated the argument that noncoding RNAs (ncRNAs) are junk transcripts that do not encode proteins. Increasing evidence suggests that small open reading frames (sORFs) in ncRNAs can encode micropeptides and polypeptides within 100 amino acids in length. Several micropeptides have been characterized and proven to have various functions in human physiology and pathology, particularly in cancer. The present review mainly highlights the latest studies on ncRNA-encoded micropeptides in different cancers and categorizes them based on their subcellular localization, thereby providing a theoretical basis for micropeptide applications in the early diagnosis and prognosis of cancer and as therapeutic targets. However, considering the inherent characteristics of micropeptides and the limitations of the assay technology methods, more detailed information is warranted.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , Proteínas , Peptídeos/genética , RNA não Traduzido , Neoplasias/genética , Fases de Leitura Aberta/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-37788825

RESUMO

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

16.
Rev Esp Enferm Dig ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882227

RESUMO

Endoscopic treatment has become a preferred method for neuroendocrine tumors (NETs) of the gastrointestinal tract.Here we report a 72-year-old female with a duodenal neuroendocrine tumor treated by ligation-assisted endoscopic mucosal resection. This treatment was effectively used to cure the duodenal NETs and ensured complete resection without residual positive margins. This case report is rare.

17.
J Pharm Pharm Sci ; 26: 11699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854323

RESUMO

Purpose: Dexmedetomidine exerts a sedative effect by promoting the sleep pathway endogenously and producing a state similar to N2 sleep. This study aimed to study the efficacy and safety of dexmedetomidine nasal spray in the treatment of postoperative sleep disturbance. Methods: This study enrolled 120 participants [men and women; age, 18-40 years; American Society of Anesthesiologists grade, I or II] who underwent maxillofacial surgery under general anesthesia through nasotracheal intubation. The participants were randomly divided into three groups: blank control group (BC group), 1.0 µg/kg dexmedetomidine group (1.0 Dex group), and 1.5 µg/kg dexmedetomidine group (1.5 Dex group), with 40 patients allocated to each group. At 21:30 on the night after the operation, the intervention groups were administered their corresponding doses of dexmedetomidine nasal spray. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate the baseline sleep status of participants 1 month preoperatively and on the night after the operation. Polysomnography (PSG) was used to record the sleep status on the night after the operation. We recorded the rescue times of sedative and analgesic drugs on the first night after surgery, adverse reactions, total hospital stay duration, and total costs. Results: Compared with patients in the BC group, those in 1.0 Dex and 1.5 Dex groups had longer N2 sleep duration, were awake for a shorter time after dose administration, woke up less often, and had significantly improved sleep efficiency (p < 0.05). Compared with the BC group, the PSQI scores of 1.0 Dex and 1.5 Dex groups were significantly lower on the night after operation, and the proportion of PSQI > 5 was significantly lower (p < 0.05). Compared with patients in the BC group and the 1.0 Dex group, those in the 1.5 Dex group had significantly prolonged N3 sleep, reduced frequency of requiring sufentanil rescue, lower incidence of sore throat after surgery, and shorter average length of hospital stay (all, p < 0.05). Conclusion: The sleep quality of participants on the night after having undergone maxillofacial surgery was safely and effectively improved by 1.0-1.5 µg/kg dexmedetomidine atomized nasal sprays. Notably, only the latter could prolong N3 sleep. Level of Evidence II: Evidence was obtained from at least one properly designed randomized controlled trial.


Assuntos
Dexmedetomidina , Transtornos do Sono-Vigília , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Dexmedetomidina/uso terapêutico , Dexmedetomidina/efeitos adversos , Sprays Nasais , Hipnóticos e Sedativos/uso terapêutico , Analgésicos , Transtornos do Sono-Vigília/tratamento farmacológico , Método Duplo-Cego
18.
Neuron ; 111(22): 3634-3649.e7, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683629

RESUMO

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5+ (Cdh5+) cerebral vascular cells in naturally aging mice and confirmed it in human brain samples. Global or Cdh5+ cell-specific CX43 deletion in mice exacerbated BBB dysfunction during aging. The CX43-dependent effect was not due to its canonical gap junction function but was associated with reduced NAD+ levels and mitochondrial dysfunction through NAD+-dependent sirtuin 3 (SIRT3). CX43 interacts with and negatively regulates poly(ADP-ribose) polymerase 1 (PARP1). Pharmacologic inhibition of PARP1 by olaparib or nicotinamide mononucleotide (NMN) supplementation rescued NAD+ levels and alleviated aging-associated BBB leakage. These findings establish the endothelial CX43-PARP1-NAD+ pathway's role in vascular aging and identify a potential therapeutic strategy to combat aging-associated BBB leakage with neuroprotective implications.


Assuntos
Conexina 43 , NAD , Animais , Humanos , Camundongos , Envelhecimento/fisiologia , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , NAD/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo
19.
Angew Chem Int Ed Engl ; 62(46): e202312029, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37747695

RESUMO

Flue gas desulfurization is crucial for both human health and ecological environments. However, developing efficient SO2 adsorbents that can break the trade-off between adsorption capacity and selectivity is still challenging. In this work, a new type of fluorinated anion-pillared metal-organic frameworks (APMOFs) with a pillar-cage structure is fabricated through pillar-embedding into a highly porous and robust framework. This type of APMOFs comprises smaller tetrahedral cages and larger icosahedral cages interconnected by embedded [NbOF5 ]2- and [TaOF5 ]2- anions acting as pillars. The APMOFs exhibits high porosity and density of fluorinated anions, ensuring exceptional SO2 adsorption capacity and ultrahigh selectivity for SO2 /CO2 and SO2 /N2 gas mixtures. Furthermore, these two structures demonstrate excellent stability towards water, acid/alkali, and SO2 adsorption. Cycle dynamic breakthrough experiments confirm the excellent separation performance of SO2 /CO2 gas mixtures and their cyclic stability. SO2 -loaded single-crystal X-ray diffraction, Grand canonical Monte Carlo (GCMC) simulations combined with density functional theory (DFT) calculations reveal the preferred adsorption domains for SO2 molecules. The multiple-site host-guest and guest-guest interactions facilitate selective recognition and dense packing of SO2 in this hybrid porous material. This work will be instructive for designing porous materials for flue gas desulfurization and other gas-purification processes.

20.
Org Biomol Chem ; 21(33): 6681-6686, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37540130

RESUMO

We report a base-promoted cyclization with indene-dienes as two carbon building blocks toward diverse spirocyclic indene scaffolds including hexacyclic spiroindenes bearing benzo pyran motifs and pentacyclic spiroindenes containing oxindole units in high yields with excellent diastereoselectivities.

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