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1.
SLAS Technol ; : 100139, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734181

RESUMO

This study probed the importance of computed tomography perfusion (CTP) on assessing collateral circulation and prognosis in patients with acute anterior circulation large vessel occlusion (AAC-LVO) after endovascular therapy (EVT). Retrospective analysis was performed on the case data of 124 AAC-LVO patients who achieved EVT in the First People's Hospital of Lianyungang. All patients received computed tomography (CT) examination. Based on the multi-phase computed tomography angiography (mCTA) score, patients were separated into poor collateral circulation group and good collateral circulation group. Based on modified Rankin scale (mRS) score, patients were separated into good prognosis group and poor prognosis group. The receiver operating characteristic (ROC) curve was used to measure the efficacy of CTP parameters in predicting good collateral circulation or good prognosis. Correlation between CTP parameters with mCTA collateral and 90-day mRS circulation score was analyzed using the Spearman correlation analysis. The age and admission national Institutes of Health stroke scale (NIHSS) scores of the good collateral circulation group were lower than the poor collateral circulation group, and low perfusion area volume with Tmax > 6 s (VTmax>6s), infarct core area volume (VCBF<30%)and hypoperfusion intensity ratio (HIR) were also lower. The mCTA collateral cycle score was negatively related to VTmax>6 s, VCBF<30% and HIR. The area under the curve (AUC) values of VTmax>6 s and VCBF<30% and HIR for predicting good collateral circulation were 0.763, 0.884 and 0.842, respectively, which suggested that perfusion parameters VTmax>6 s, VCBF<30% and HIR could effectively indicate the status of patients' collateral circulation. Relative to the poor prognosis group, patients in the good prognosis group possessed lower admission NIHSS score, younger age, smaller final infarct volume, lower HIR, VCBF<30%, VTmax>6s, Alberta Stroke Program Early CT(ASPECT) score, and higher mCTA score. Spearman correlation analysis unveiled that ASPECT score, mCTA score and 90-day mRS were negatively correlated. The final infarct volume, perfusion parameters HIR and VCBF<30% were positively correlated with 90-day mRS. ROC analysis showed that all variates had good prognostic value for acute anterior circulation great vessel occlusion patients, while VCBF<30% and HIR had high diagnostic value for prognosis. To sum up, CTP can provide a comprehensive imaging assessment of the collateral circulation of patients with AAC-LVO and has a higher predictive value for the prognosis assessment of patients with EVT in terms of VCBF<30%, HIR score and mCTA collateral circulation score.

2.
Org Lett ; 26(17): 3509-3513, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38652867

RESUMO

Five-carbon (C5) units are the fundamental building blocks that constitute a multitude of natural products. Herein we report an unprecedented unusual C5 functionalization of indole regioselectively at the C-2-position enabled by a (2-pyridyl)sulfonyl-directing palladium-catalyzed dehydrogenative strategy with a bulk chemical 2-methyl-2-butene as a C5 source. Compared to typical C5 functionalization using pentenyl alcohols, carbonates, borates, or halides as the C5 source, the protocol not only has a low cost advantage but also is of atom and step economy.

3.
Eur J Med Chem ; 271: 116417, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38688063

RESUMO

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.


Assuntos
Artrite Reumatoide , Isoquinolinas , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Antirreumáticos/farmacologia , Antirreumáticos/química , Antirreumáticos/síntese química , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Descoberta de Drogas , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoquinolinas/química , Isoquinolinas/farmacologia , Isoquinolinas/síntese química , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologia
4.
J Clin Invest ; 134(10)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625739

RESUMO

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.


Assuntos
Nefropatias Diabéticas , Fibrose , Insuficiência Renal Crônica , Animais , Humanos , Camundongos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Camundongos Knockout , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Proteína Smad3/metabolismo , Proteína Smad3/genética , Masculino , Rim/metabolismo , Rim/patologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Regiões 3' não Traduzidas
5.
Environ Health ; 23(1): 38, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609943

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.


Assuntos
Artrite Reumatoide , Fluorocarbonos , Adulto , Feminino , Masculino , Humanos , Inquéritos Nutricionais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/epidemiologia , Razão de Chances , Autorrelato
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 382-388, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660840

RESUMO

OBJECTIVE: To confirm the direct regulatory effect of WTAP-mediated RNA m6A modification on the KDM4B gene in t (8;21) acute myeloid leukemia (AML) cells through MeRIP combined with reverse transcription real-time quantitative PCR (RT-qPCR) technology. METHODS: The lentivirus-mediated shRNA target WTAP or KDM4B gene was used to transfect the t (8;21) AML cell lines: Kasumi-1 and SKNO-1, and cells transfected with randomly shuffled shRNA as the control. Using the Ultrapure RNA Extraction Kit (DNase I) to extract RNA. The Magna MeRIPTM m6A Kit was used to enrich methylated modified fragments, and detect the m6A methylated RNA regions by RT-qPCR, and the protein and mRNA expression levels of WTAP and KDM4B in cells were detected by Western blot and reverse transcription real-time quantitative PCR (RT-qPCR). Colony formation assays were used to detect the colony ability of cells in vitro. RESULTS: Silencing the expression of WTAP in Kasumi-1 cells, the enrichment of m6A methylation modification was significantly decreased in the 3'UTR of KDM4B mRNA(P < 0.01), and the protein(P < 0.001) and mRNA (Kasumi-1:P < 0.001; SKNO-1: P < 0.01) expression levels of KDM4B were also significantly inhibited in Kasumi-1 and SKNO-1 cells upon WTAP knockdown (all P < 0.01), accompanied by a significant decrease in the colony-forming ability of both cell lines (both P < 0.01). CONCLUSION: In t(8;21) AML cell lines, WTAP could regulate the expression of KDM4B by regulating the m6A modification of the 3'UTR of KDM4B mRNA, and silencing the expression of KDM4B could inhibit the cellular proliferation in vitro.


Assuntos
Histona Desmetilases com o Domínio Jumonji , Leucemia Mieloide Aguda , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Leucemia Mieloide Aguda/genética , Linhagem Celular Tumoral , Metilação , RNA Mensageiro/genética , RNA Interferente Pequeno/genética
7.
Int J Ophthalmol ; 17(4): 713-720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638257

RESUMO

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

8.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1260-1265, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621973

RESUMO

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.


Assuntos
Artemisia annua , Artemisininas , Lactonas , Artemisia annua/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Melhoramento Vegetal , Artemisininas/análise , Aldeídos
9.
Front Neurol ; 15: 1353275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38682035

RESUMO

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

10.
Phys Rev Lett ; 132(15): 152502, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38682998

RESUMO

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νßß) search. In addition, the two-neutrino case (2νßß) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νßß and 0νßß of ^{134}Xe half-lives, with limits of 2.8×10^{22} yr and 3.0×10^{23} yr at 90% confidence level, respectively. The 2νßß (0νßß) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

11.
Oncol Lett ; 27(6): 269, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38686356

RESUMO

Human epidermal growth factor receptor 2 (HER2)+ breast cancer is characterized by high malignancy and poor prognosis. Long non-coding (lnc)RNAs are crucial in breast cancer progression and prognosis, especially in tumor-associated immune processes. The present study aimed to elucidate novel lncRNAs related to immune function that could serve as biomarkers for both diagnosis and prognosis of this cancer subtype. Using data from The Cancer Genome Atlas and The Immunology Database and Analysis Portal, correlation analysis was performed to identify differentially expressed lncRNAs and immune-related genes. Through receiver operating characteristic analysis, the diagnostic value of specific lncRNAs was identified and evaluated, with a focus on their capacity to distinguish between cancerous and non-cancerous states. The present research revealed 22 differentially expressed lncRNAs and 23 differentially expressed immune-related genes, with 19 immune-related lncRNAs. A total of 13 of these lncRNAs demonstrated diagnostic relevance. In particular, it was demonstrated that the expression of lncRNA CTC-537E7.2 was significantly correlated with patient survival, suggesting its potential as a prognostic marker. Additionally, the expression of lncRNA CTC-537E7.2 was significantly correlated with clinical parameters, such as hormone receptor status and patient demographics. Moreover, it exhibited associations with four distinct immune cell types and demonstrated involvement in the Janus kinase-signal transducer and activator of transcription pathway. Further assessment by in situ hybridization confirmed the increased expression of lncRNA CTC-537E7.2 in samples from HER2+ patients, reinforcing its significance. In summary, the present study uncovered a novel prognostic biomarker for HER2+ breast cancer, thereby laying the groundwork for investigating the underlying molecular mechanisms driving the development of this subtype of breast cancer.

12.
Org Lett ; 26(18): 3878-3882, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38678578

RESUMO

The synthesis of complex alkanes by the tetrafunctionalization of alkynes is limited and challenging. Herein, an unprecedented efficient geminal diazidation and dibromination of terminal alkynes is developed, which provides novel access to structurally diverse organic azides. The approach has exclusive chemo- and regioselectivity and features mild reaction conditions, good tolerance of various functional groups, and more crucially, no metal involved in the reaction, thereby benefiting the late-stage decoration of medicinal molecules. A mechanistic study showed that the current geminal diazidation and dibromination proceeds via a radical pathway.

13.
Food Funct ; 15(9): 5088-5102, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38666497

RESUMO

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.


Assuntos
Hipertensão , Núcleo Hipotalâmico Paraventricular , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Acoplados a Proteínas G , Ácido Taurocólico , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
14.
Toxicol Appl Pharmacol ; 486: 116946, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679241

RESUMO

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

15.
Environ Sci Pollut Res Int ; 31(18): 27172-27191, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503959

RESUMO

Mitigating carbon emissions from crop production is essential for addressing global warming. At a macro-level, existing studies have often relied on the calculation of carbon emission intensity of crop production to understand comparable carbon effects between regions. However, this approach obscures the differences in crop planting scale and natural attributes across regions, leaving room for improvement in the methods and scope of analysis. To extend the existing research, we proposed an idea for calculating the carbon emission density of crop production based on planting area. Additionally, we developed an analytical framework for driving factors of carbon emission density of crop production from a spatial interaction perspective. The provincial carbon emission density of crop production in mainland China between 2000 and 2020 was calculated, and spatial econometric models were utilized to investigate the spatial autocorrelation and driving factors. The results indicate that the national average carbon emission density of crop production was 1.462 t/hm2 annually. Over 21 years, the carbon emission density of agricultural materials, rice cultivation, soil management, and straw burning evolved from 0.384 to 0.470 t/hm2, 0.409 to 0.367 t/hm2, 0.171 to 0.169 t/hm2, and 0.317 to 0.448 t/hm2, respectively. The global Moran's index indicated a positive spatial autocorrelation of carbon emission density of crop production and the subdivided carbon sources among provinces. Regarding direct effects, an increase in the proportion of paddy fields in cropland composition and irrigation efficiency would significantly promote the carbon emission density, while factors such as cropland area, multiple cropping, agricultural personnel numbers, departmental proportion, and disaster degree would decrease the local carbon emission density. Certain factors, such as cropland area and agricultural disasters, had a spatial spillover effect on carbon emission density between provinces. The study suggests harnessing key drivers and spatial spillover effects to achieve regional low-carbon crop production.


Assuntos
Carbono , Produção Agrícola , Produtos Agrícolas , China , Carbono/análise , Produção Agrícola/métodos , Agricultura , Análise Espacial , Monitoramento Ambiental
16.
Sci Total Environ ; 923: 171423, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442762

RESUMO

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Feminino , Gravidez , Humanos , Material Particulado/toxicidade , Material Particulado/análise , DNA Mitocondrial/análise , Poluição do Ar/análise , Variações do Número de Cópias de DNA , Mitocôndrias , Exposição Ambiental/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise
17.
Abdom Radiol (NY) ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551668

RESUMO

BACKGROUND: To identify reliable magnetic resonance imaging (MRI) features that can differentiate confluent fibrosis (CF) from infiltrative hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted on Twenty CF patients and 28 infiltrative HCC patients who underwent upper abdomen MRI scans. The imaging features of lesions were analyzed, and the apparent diffusion coefficient (ADC) of lesions were measured. Accuracy, sensitivity and specificity for the diagnosis of CF were calculated for each category individually and combined. RESULTS: Compared to infiltrative HCC, hepatic capsular retraction at the site of lesion, hepatic volume loss at the site of lesion and "nodular surround sign" were more common in patients with CF (all P < 0.001). Hepatic volume loss at the site of lesion, no or mild enhancement in arterial phase, and hyper-enhancing in delayed phase to the background parenchyma showed superior diagnostic accuracy (83.3%, 85.4%, 97.9%, respectively). When the lesion exhibited hepatic volume loss at the site of lesion or no or mild enhancement in arterial phase or hyper-enhancing in delayed phase, a sensitivity of 100.0% for the diagnosis of CF was achieved. When the lesion was positive for any two of three categories, or positive for all three categories, a specificity of 100.0% was achieved. The ADC values of CF were higher than those of infiltrative HCC (P < 0.001). CONCLUSION: The combination of the hepatic volume loss at the site of lesion, no or mild enhancement in arterial phase, and hyper-enhancing in delayed phase to the background parenchyma can be considered reliable MR features for the diagnosis of CF, as they allow differentiation from infiltrative HCC.

18.
Eur J Radiol Open ; 12: 100555, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38544918

RESUMO

Objective: To build a radiomics signature based on MRI images and evaluate its capability for preoperatively identifying the benign and malignant Soft tissue neoplasms (STTs). Materials and methods: 193 patients (99 malignant STTs and 94 benign STTs) were at random segmented into a training cohort (69 malignant STTs and 65 benign STTs) and a validation cohort (30 malignant STTs and 29 benign STTs) with a portion of 7:3. Radiomics features were extracted from T2 with fat saturation and T1 with fat saturation and gadolinium contrast images. Radiomics signature was developed by the least absolute shrinkage and selection operator (LASSO) logistic regression model. The receiver that operated characteristics curve (ROC) analysis was used to assess radiomics signature's prediction performance. Inner validation was performed on an autonomous cohort that contained 40 patients. Results: A radiomics was developed by a total of 16 radiomics features (5 original shape features and 11 were wavelet features) achieved favorable predictive efficacy. Malignant STTs showed higher radiomics score than benign STTs in both training cohort and validation cohort. A good prediction performance was shown by the radiomics signature in both training cohorts and validation cohorts. The training cohorts and validation cohorts had an area under curves (AUCs) of 0.885 and 0.841, respectively. Conclusions: A radiomics signature based on MRI images can be a trustworthy imaging biomarker for identification of the benign and malignant STTs, which could help guide treatment strategies.

19.
Front Oncol ; 14: 1303686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347843

RESUMO

Background: Total mesorectal excision (TME), represents a key technique in radical surgery for rectal cancer. This study aimed to construct a preoperative nomogram for predicting the surgical difficulty of laparoscopic total mesorectal excision (L-TME) and to investigate whether there were potential benefits of robotic TME (R-TME) for patients with technically challenging rectal cancer. Methods: Consecutive mid-low rectal cancer patients receiving total mesorectal excision were included. A preoperative nomogram to predict the surgical difficulty of L-TME was established and validated. Patients with technically challenging rectal cancer were screened by calculating the prediction score of the nomogram. Then patients with technically challenging rectal cancer who underwent different types of surgery, R-TME or L-TME, were analyzed for comparison. Results: A total of 533 consecutive patients with mid-low rectal cancer who underwent TME at a single tertiary medical center between January 2018 and January 2021 were retrospectively enrolled. Multivariable analysis demonstrated that mesorectal fat area, intertuberous distance, tumor size, and tumor height were independent risk factors for surgical difficulty. Subsequently, these variables were used to construct the nomogram model to predict the surgical difficulty of L-TME. The area under the receiver operating characteristic curve of the nomogram was 0.827 (95% CI 0.745 - 0.909) and 0.809 (95% CI 0.674- 0.944) in the training and validation cohort, respectively. For patients with technically challenging rectal cancer, R-TME was associated with a lower diverting ileostomy rate (p = 0.003), less estimated blood loss (p < 0.043), shorter procedure time (p = 0.009) and shorter postoperative hospital stay (p = 0.037). Conclusion: In this study, we established a preoperative nomogram to predict the surgical difficulty of L-TME. Furthermore, this study also indicated that R-TME has potential technical advantages for patients with technically challenging rectal cancer.

20.
J Ultrasound ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311662

RESUMO

PURPOSE: The purpose of this study was to investigate a novel posterior intra-articular hip injection approach while discussing the clinical pearls for methodology, accuracy, and associated adverse events. The goal was to investigate if this approach could potentially be used in those where the typical anterior access would be challenging. MATERIALS AND METHODS: 10 adults (age > 18 years) who were referred to a tertiary outpatient clinic for hip injection due to hip osteoarthritis or femoral acetabular impingement with labral tearing to a single academic sports medicine clinic. Patients were placed in prone position. Posterior structures were identified using a curvilinear transducer. A 22 gauge 3.5-6-inch spinal needle was advanced in-plane to the transducer towards the hip capsule at the head-neck junction of the femur from inferolateral to superomedial. A fluoroscopic arthrogram was obtained to evaluate needle placement accuracy. Location of the needle, direction of contrast flow, the rate of conversion to an anterior portal, and adverse events were analyzed. RESULTS: A fluoroscopic arthrogram was obtained after the first attempt in nine patients (90%). One patient (10%) was converted to the anterior approach due to inability to obtain the expected arthrogram. Two patients (20%) demonstrated mild adverse events. CONCLUSION: Ultrasound-guided posterior approach hip injection is accurate and without serious adverse events in our study. The posterior approach can be considered as an alternative approach for patients who cannot tolerate or may have technical difficulty with an anterior approach.

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