Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.441
Filtrar
1.
Int J Biol Sci ; 20(7): 2422-2439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725842

RESUMO

Background & Aims: Reactive oxygen species (ROS) act as modulators triggering cellular dysfunctions and organ damage including liver fibrosis in which hepatic stellate cell (HSC) activation plays a key role. Previous studies suggest that microRNA-144 (miR-144) acts as a pro-oxidant molecule; however, whether and how miR-144 affects HSC activation and liver fibrosis remain unknown. Methods: Carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced experimental liver fibrosis models were used. Hepatic miR-144 expression was analyzed by miRNA in situ hybridization with RNAscope probe. The in vivo effects of silencing or overexpressing miR-144 were examined with an adeno-associated virus 6 (AAV6) carrying miR-144 inhibitor or mimics in fibrotic mouse experimental models. Results: In this study, we demonstrated that ROS treatment significantly upregulated miR-144 in HSCs, which further promoted HSC activation in vitro. Interestingly, miR-144 was preferentially elevated in HSCs of experimental liver fibrosis in mice and in human liver fibrotic tissues. Furthermore, in vivo loss or gain-of-function experiments via AAV6 carrying miR-144 antagomir or agomir revealed that blockade of miR-144 in HSCs mitigated, while overexpression of miR-144 in HSCs accelerated the development of experimental liver fibrosis. Mechanistically, SIN3 transcription regulator family member A (SIN3A), a transcriptional repressor, was identified to be the target of miR-144 in HSCs. MiR-144 downregulated Sin3A, and in line with this result, specific knockdown of Sin3a in HSCs remarkedly activated p38 MAPK signaling pathway to promote HSC activation, eventually exacerbating liver fibrosis. Conclusions: Oxidative stress-driven miR-144 fuels HSC activation and liver fibrogenesis by limiting the SIN3A-p38 axis. Thus, a specific inhibition of miR-144 in HSCs could be a novel therapeutic strategy for the treatment of liver fibrosis.


Assuntos
Células Estreladas do Fígado , Cirrose Hepática , MicroRNAs , Estresse Oxidativo , Espécies Reativas de Oxigênio , Complexo Correpressor Histona Desacetilase e Sin3 , Proteínas Quinases p38 Ativadas por Mitógeno , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos , Humanos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Complexo Correpressor Histona Desacetilase e Sin3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Tetracloreto de Carbono
2.
Front Immunol ; 15: 1312380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726002

RESUMO

Objective: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT). Methods: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model's effectiveness. Results: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906). Conclusion: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso , Biomarcadores Tumorais , Resultado do Tratamento , Imunoterapia/métodos
3.
BMC Psychiatry ; 24(1): 351, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730360

RESUMO

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.


Assuntos
Depressão , Obesidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Obesidade/epidemiologia , Depressão/epidemiologia , Depressão/sangue , Idoso , Estudos Longitudinais , Fatores de Risco , Índice de Massa Corporal , Lipídeos/sangue , Circunferência da Cintura , População do Leste Asiático
4.
Arthritis Res Ther ; 26(1): 96, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711064

RESUMO

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.


Assuntos
Acrilamidas , Gota , Histona Desacetilases , Macrófagos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenilenodiaminas , Ácido Úrico , Animais , Ácido Úrico/toxicidade , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/deficiência , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Gota/metabolismo , Gota/patologia , Camundongos , Inflamação/metabolismo , Inflamação/induzido quimicamente , Masculino , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/metabolismo , Artrite Gotosa/patologia , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos
5.
Front Mol Neurosci ; 17: 1394886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745725

RESUMO

Aims: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. Main methods: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Key findings: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Significance: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.

6.
Front Public Health ; 12: 1382384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746004

RESUMO

Objective: Frailty and activities of daily living (ADL) disability are common conditions among older population. Studies on the bidirectional relationship between frailty and ADL are limited. The current study examined the cross-sectional and longitudinal associations between frailty and ADL in middle-aged and older Chinese individuals. Methods: The data was collected through the China Health and Retirement Longitudinal Study (CHARLS), conducted in 2011, 2013, and 2015, encompassing 17,284 individuals aged ≥45 years. We excluded individuals without follow-up data. 2,631 participants finished the baseline survey. The definition of ADL disability encompasses difficulty in engaging in either basic activities of daily living (BADL) or instrumental activities of daily living (IADL). Frailty was assessed according to the Fried criteria. Logistic regression was utilized to examine odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the cross-sectional relationships between ADL with frailty at baseline. The prediction effects were explored using Cox proportional hazards analysis, testing hazard ratios (HRs) and 95%CIs. Results: In cross-sectional analysis, BADL [OR = 6.660 (4.519-9.815)], IADL [OR = 5.950 (4.490-7.866)], and ADL [OR = 5.658 (4.278-7.483)] exhibited significant associations with frailty; frailty demonstrated significant associations with BADL [OR = 6.741 (4.574-9.933)], IADL [OR = 6.042 (4.555-8.016)] and ADL [OR = 5.735 (4.333-7.591)]. In longitudinal analysis, IADL and ADL were significantly associated with frailty in participants without baseline frailty in the short-term period [IADL: HR = 1.971 (1.150-3.379), ADL: HR = 1.920 (1.146-3.215)], IADL exhibited a significant association with frailty in the long-term period [HR = 2.056 (1.085-3.895)]. There was no significant link observed between frailty and an elevated risk of disability onset in BADL, IADL and ADL during the short-term period. When considering the long-term perspective, frailty exhibited a significant association with an elevated risk of disability onset in BADL [HR= 1.820 (1.126-2.939)] and IADL [HR = 1.724 (1.103-2.694)]. Conclusion: In middle-aged and older adults, ADL and IADL disability predicted frailty after 2-year follow-up, IADL disability predicted frailty after 4-year follow-up. Moreover, frailty did not predict BADL, IADL and ADL disability after 2-year follow-up. However, frailty predicted BADL and IADL disability after 4-year follow-up.


Assuntos
Atividades Cotidianas , Idoso Fragilizado , Fragilidade , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , China/epidemiologia , Estudos Transversais , Estudos Longitudinais , Idoso Fragilizado/estatística & dados numéricos , Seguimentos , Idoso de 80 Anos ou mais , Avaliação Geriátrica/estatística & dados numéricos , População do Leste Asiático
7.
Artigo em Inglês | MEDLINE | ID: mdl-38744687

RESUMO

Three-dimensional (3D) vector magnetic sensors play a significant role in a variety of industries, especially in the automotive industry, which enables the control of precise position, angle, and rotation of motion elements. Traditional 3D magnetic sensors integrate multiple sensors with their sensing orientations along the three coordinate axes, leading to a large size and inevitable nonorthogonal misalignment. Here, we demonstrate a wide linearity range 3D magnetic sensor utilizing a single L10-FePt Hall-bar device, whose sensitivity is 291 VA-1 T-1 in the z-axis and 27 VA-1 T-1 in the in-plane axis. Based on the spin-orbit torque-dominated magnetization reversal, the linear response of anomalous Hall resistance within a large linear range (±200 Oe) for the x, y, and z components of magnetic fields has been obtained, respectively. Typically, it exhibits a relatively lower magnetic noise level of 7.9 nV at 1 Hz than previous results, improving measurement resolution at the low frequency. Furthermore, we provide a straightforward approach for noncontact angular position detection based on a single Hall-bar device, which shows great potential for application in rotational motion control.

8.
Sci Rep ; 14(1): 10901, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740846

RESUMO

To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut­off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P < 0.05). According to ROC analysis, the TyG index was the best predictor of T2D among males (AUC = 0.780, 95% CI 0.761, 0.799) and females (AUC = 0.782, 95% CI 0.764, 0.799). The AUC values of the 13 indicators were higher than 0.5, indicating that they have predictive values for T2D in middle-aged and elderly Chinese. The 13 obesity- and lipid-related indices can predict the risk of T2D in middle­aged and elderly Chinese. Among 13 indicators, the TyG index is the best predictor of T2D in both males and females. TyG-WC, TyG-BMI, TyG-WHtR, LAP, and CVAI all outperformed BMI, WC, and WHtR in predicting T2D.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Obesidade , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Obesidade/sangue , Obesidade/diagnóstico , China/epidemiologia , Estudos Transversais , Circunferência da Cintura , Curva ROC , Lipídeos/sangue , Estudos Longitudinais , Fatores de Risco , População do Leste Asiático
9.
BMC Biol ; 22(1): 111, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741075

RESUMO

BACKGROUND: Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown. RESULTS: In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for the biosynthesis of JHB3 and JH III in D. melanogaster. The Cyp6g2 is predominantly expressed in the corpus allatum (CA), concurring with the expression pattern of jhamt, another well-studied gene that is crucial in the last steps of JH biosynthesis. Mutation in Cyp6g2 leads to severe disruptions in larval-pupal metamorphosis and exhibits reproductive deficiencies, exceeding those seen in jhamt mutants. Notably, Cyp6g2-/-::jhamt2 double mutants all died at the pupal stage but could be rescued through the topical application of JH analogs. JH titer analyses revealed that both Cyp6g2-/- mutant and jhamt2 mutant lacking JHB3 and JH III, while overexpression of Cyp6g2 or jhamt caused a significant increase in JHB3 and JH III titer. CONCLUSIONS: These findings collectively established that Cyp6g2 as the major JH epoxidase in the higher dipterans and laid the groundwork for the further understanding of JH biosynthesis. Moreover, these findings pave the way for developing specific Cyp6g2 inhibitors as insect growth regulators or insecticides.


Assuntos
Drosophila melanogaster , Hormônios Juvenis , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Hormônios Juvenis/biossíntese , Hormônios Juvenis/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Larva/crescimento & desenvolvimento , Larva/genética , Metamorfose Biológica/genética , Corpora Allata/metabolismo , Pupa/crescimento & desenvolvimento , Pupa/genética , Pupa/metabolismo , Oxirredutases
10.
J Am Chem Soc ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718348

RESUMO

PEDOT: PSS has been widely used as a hole extraction layer (HEL) in organic solar cells (OSCs). However, their acidic nature can potentially corrode the indium tin oxide (ITO) electrode over time, leading to adverse effects on the longevity of the OSCs. Herein, we have developed a class of biphosphonic acid molecules with tunable dipole moments for self-assembled monolayers (SAMs), namely, 3-BPIC(i), 3-BPIC, and 3-BPIC-F, which exhibit an increasing dipole moment in sequence. Compared to centrosymmetric 3-BPIC(i), the axisymmetric 3-BPIC and 3-BPIC-F exhibit higher adsorption energies (Eads) with ITO, shorter interface spacing, more uniform coverage on ITO surface, and better interfacial compatibility with the active layer. Thanks to the incorporation of fluorine atoms, 3-BPIC-F exhibits a deeper highest occupied molecular orbital (HOMO) energy level and a larger dipole moment compared to 3-BPIC, resulting in an enlarged work function (WF) for the ITO/3-BPIC-F substrate. These advantages of 3-BPIC-F could not only improve hole extraction within the device but also lower the interfacial impedance and reduce nonradiative recombination at the interface. As a result, the OSCs using SAM based on 3-BPIC-F obtained a record high efficiency of 19.71%, which is higher than that achieved from the cells based on 3-BPIC(i) (13.54%) and 3-BPIC (19.34%). Importantly, 3-BPIC-F-based OSCs exhibit significantly enhanced stability compared to that utilizing PEDOT:PSS as HEL. Our work offers guidance for the future design of functional molecules for SAMs to realize even higher performance in organic solar cells.

11.
Cancer Biol Med ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38712819

RESUMO

OBJECTIVE: To investigate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). METHODS: A total of 155 patients with CHB-related HCC who received ICI-based therapy (in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were evaluated. Patients were divided into two groups: MASLD concurrent with CHB [MASLD-CHB] (n = 38), and CHB (n = 117). RESULTS: The median progression-free survival (PFS, 6.9 months vs. 9.3 months; P = 0.001), progressive disease (57.89% vs. 37.61%; P = 0.028), and disease control rate (42.11% vs. 62.39%; P = 0. 028) in the MASLD-CHB group were significantly worse than the CHB group. The median overall survival was not attained. The percentage of CD4+PD1+ (17. 56% vs. 8.89%; P < 0.001) and CD8+PD1+ T cells (10.50% vs. 7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB group. Concurrent MASLD [hazard ratio (HR) = 1.921; 95% CI, 1.138-3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment (HR = 2.412; 95% CI, 1.360-4.279; P = 0.003) were independent risk factors for PFS in all patients. CONCLUSIONS: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

12.
Genome Biol ; 25(1): 116, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715020

RESUMO

BACKGROUND: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. RESULTS: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. CONCLUSIONS: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.


Assuntos
Genoma , Variação Estrutural do Genoma , Animais , Sus scrofa/genética , Polimorfismo de Nucleotídeo Único , Suínos/genética , Mapeamento Cromossômico
13.
Sci Total Environ ; 931: 172866, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705291

RESUMO

Tetracycline antibiotics (TCs) are extensively used in clinical medicine, animal husbandry, and aquaculture because of their cost-effectiveness and high antibacterial efficacy. However, the presence of TCs residues in the environment poses risks to humans. In this study, an inner filter effect (IFE) fluorescent probe, 2,2'-(ethane-1,2-diylbis((2-((2-methylquinolin-8-yl)amino)-2-oxoethyl)azanediyl))diacetic acid (MQDA), was developed for the rapid detection of Eu3+ within 30 s. And its complex [MQDA-Eu3+] was successfully used for the detection of TCs. Upon coordination of a carboxyl of MQDA with Eu3+ to form a [MQDA-Eu3+] complex, the carboxyl served as an antenna ligand for the effective detection of Eu3+ to intensify the emission intensity of MQDA via "antenna effect", the process was the energy absorbed by TCs via UV excitation was effectively transferred to Eu3+. Fluorescence quenching of the [MQDA-Eu3+] complex was caused by the IFE in multicolor fluorescence systems. The limits of detection of [MQDA-Eu3+] for oxytetracycline, chlorotetracycline hydrochloride, and tetracycline were 0.80, 0.93, and 1.7 µM in DMSO/HEPES (7:3, v/v, pH = 7.0), respectively. [MQDA-Eu3+] demonstrated sensitive detection of TCs in environmental and food samples with satisfactory recoveries and exhibited excellent imaging capabilities for TCs in living cells and zebrafish with low cytotoxicity. The proposed approach demonstrated considerable potential for the quantitative detection of TCs.

14.
Sci Rep ; 14(1): 10220, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702424

RESUMO

The purpose of the study was to determine whether changes in body mass index (BMI) and waist circumference (WC) in middle-aged and elderly Chinese are associated with metabolic syndrome. In this cohort investigation, 3697 middle-aged and elderly people aged 45 or over were recruited from the China Health and Retirement Longitudinal Study (CHARLS). The National Cholesterol Education Program Adult Treatment Panel III (2005) defined metabolic syndrome (MetS). With Cox regression analysis, we calculated hazard ratio (HR) and 95% confidence intervals (CIs) for MetS based on BMI-WC change categories. To assess the prevalence of MetS, the changes in BMI and WC levels were classified into four quartiles based on their relative and absolute changes. In subjects whose BMI and WC decreased (HR = 0.338; 95% CIs 0.264, 0.433) as well as those whose BMI increased and their WC decreased (HR = 0.375; 95% CIs 0.228, 0.499), metabolic syndrome risk was significantly lower compared with those with increases in both BMI and WC. Regarding the absolute changes in BMI, the lowest percentile of BMI was significantly lower in both males (HR = 0.302; 95% CIs 0.204, 0.448) and females (HR = 0.486; 95% CIs 0.354, 0.667) for the risk of metabolic syndrome. Similar results were observed in the absolute changes in WC, with the lowest quantile of WC having a significant impact on MetS risk in males (HR = 0.170; 95% CIs 0.107, 0.270) and females (HR = 0.303; 95% CIs 0.217, 0.424). The risk of metabolic syndrome was significantly associated with changes in BMI and WC in middle-aged and elderly Chinese. A reduced BMI and WC are associated with lower metabolic syndrome risks in middle-aged and elderly people.


Assuntos
Índice de Massa Corporal , Síndrome Metabólica , Circunferência da Cintura , Humanos , Síndrome Metabólica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Estudos Longitudinais , Fatores de Risco , Prevalência , Povo Asiático , População do Leste Asiático
15.
Surg Endosc ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714570

RESUMO

BACKGROUND: This study aims to analyze the influencing factors of postoperative Low Anterior Resection Syndrome (LARS) in patients with middle and low rectal cancer who underwent robotic surgery. It also seeks to predict the probability of LARS through a visual, quantitative, and graphical nomogram. This approach is expected to lower the risk of postoperative LARS in these patients and improve their quality of life through effective prevention and early intervention. PATIENTS AND METHODS: This research involved patients with middle and low rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to October 2022. A series of intestinal dysfunction symptoms arising from postoperative rectal cancer were diagnosed and graded using LARS scoring criteria. After the initial screening of all variables related to LARS with Lasso regression, they were included in logistic regression for further univariate and multivariate analysis to identify independent risk factors for LARS. A prediction model was then constructed. RESULTS: The study included 358 patients. The parameters identified by Lasso regression included obstruction, BMI, tumor localization, maximum tumor diameter, AJCC stage, stoma, neoadjuvant therapy (NAT), and postoperative adjuvant therapy (AT). Univariate and multivariate analyses indicated that a higher BMI, lower tumor localization, higher AJCC stage, neoadjuvant therapy, and postoperative adjuvant therapy were independent risk factors for total LARS. The AUC of the prediction nomogram was 0.834, with a sensitivity of 0.825 and specificity of 0.741. The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve fit the diagonal well. CONCLUSION: Higher BMI, lower tumor localization, higher AJCC stage, neoadjuvant therapy, and adjuvant therapy were identified as independent risk factors for total LARS. A new predictive nomogram for postoperative LARS in patients with middle and low rectal cancer undergoing robotic surgery was developed, proving to be stable and reliable. This tool will assist clinicians in managing the postoperative treatment of these patients, facilitating better clinical decision-making and maximizing patient benefits.

16.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38715408

RESUMO

Speech comprehension in noise depends on complex interactions between peripheral sensory and central cognitive systems. Despite having normal peripheral hearing, older adults show difficulties in speech comprehension. It remains unclear whether the brain's neural responses could indicate aging. The current study examined whether individual brain activation during speech perception in different listening environments could predict age. We applied functional near-infrared spectroscopy to 93 normal-hearing human adults (20 to 70 years old) during a sentence listening task, which contained a quiet condition and 4 different signal-to-noise ratios (SNR = 10, 5, 0, -5 dB) noisy conditions. A data-driven approach, the region-based brain-age predictive modeling was adopted. We observed a significant behavioral decrease with age under the 4 noisy conditions, but not under the quiet condition. Brain activations in SNR = 10 dB listening condition could successfully predict individual's age. Moreover, we found that the bilateral visual sensory cortex, left dorsal speech pathway, left cerebellum, right temporal-parietal junction area, right homolog Wernicke's area, and right middle temporal gyrus contributed most to prediction performance. These results demonstrate that the activations of regions about sensory-motor mapping of sound, especially in noisy conditions, could be sensitive measures for age prediction than external behavior measures.


Assuntos
Envelhecimento , Encéfalo , Compreensão , Ruído , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala , Humanos , Adulto , Percepção da Fala/fisiologia , Masculino , Feminino , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Compreensão/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Envelhecimento/fisiologia , Mapeamento Encefálico/métodos , Estimulação Acústica/métodos
17.
J Clin Nurs ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716811

RESUMO

BACKGROUND: While there exists an ample body of research in international contexts focused on the characterization and quantification of infertility psychological distress, the level of scholarly scrutiny directed towards this phenomenon within the context of China remains scant. AIMS AND OBJECTIVES: To investigate the formation and developmental processes of psychological distress associated with infertility and infertility treatment among women within the Chinese cultural context and to construct a theoretical framework that elucidates this phenomenon. DESIGN: Qualitative approach with grounded theory methodology. METHODS: This study was conducted within the reproductive medicine department of a tertiary-level hospital located in central China from May to August 2023. Twenty-seven women who experienced infertility and underwent assisted reproductive treatment (ART) were interviewed. The interview sessions spanned durations ranging from 20 min to 1 h and 35 min. Data analysis included open coding, axial coding and selective coding. The study is reported using the COREQ checklist. RESULTS: The infertility psychological distress experienced by women undergoing ART is a socially constructed phenomenon influenced by a dynamic interplay of forces that construct and conciliate it. The formation and progression of infertility psychological distress are rooted in the process of self-construction. A Middle-Ranged Theory titled 'self-reconstruction under the dome of infertility and infertility treatment' (SUDIT theory) was developed to explain this phenomenon. Within this framework, infertility psychological distress manifests across three distinct phases under the gambling of the constructive force and conciliative force: (1) distress of disrupting the former self; (2) distress linked to the struggling present self; and (3) the renewed-self harmonized with distress. CONCLUSIONS: It is imperative for healthcare professionals and policymakers to acknowledge the socially constructed nature of infertility psychological distress, and proactively implement measures aimed at ameliorating it. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

18.
PLoS One ; 19(5): e0296496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701104

RESUMO

The spatial characteristics of element flow and its spillover are important topics in economics, sociology, and geography, and significant to the promotion of the coordinated development of urban agglomerations. To study element flow in the Lanxi urban agglomeration and its effect to economic development, the spatial network characteristics and economic spillover effect were studied using the methods of spatial network analysis, the spatial Durbin model, and spatial effect decomposition. The results showed that (1) the scale of element flow in the Lanxi urban agglomeration is in an unbalanced distribution state, the scale of element flow in Lanzhou and Xining is higher than that in surrounding cities, and the connection between surrounding cities is also higher than that between other cities; (2) the network structure of element flow in the Lanxi urban agglomeration is relatively intensive, with Lanzhou and Xining as the center of element concentration, which indicates an obvious 'center periphery' structure, and gradually spreads from the core area to the surrounding areas; and (3) the element concentration level of the Lanxi urban agglomeration has a significant positive spillover effect, which plays a significant role in driving the development of surrounding cities. Other factors, such as the social consumption level, have significant direct effects, whereas the industrial structure and residents' income have significant direct and spillover effects, and are the main factors that affect the coordinated development of the regional economy.


Assuntos
Cidades , China , Humanos , Desenvolvimento Econômico , Urbanização , Análise Espacial
19.
Sci Total Environ ; 931: 172889, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697535

RESUMO

Adjacent near-wall heat sources are widely used in indoor environments. It is important to investigate the particle deposition under the influence of coupled thermal plumes arising from adjacent near-wall heat sources to improve indoor air quality and control harmful particle deposition. Thus, this study scrutinizes the behavior of thermal plumes emanating from adjacent near-wall heat sources, focusing on the deposition of particles with diameters of 0.3 µm, 0.5 µm, 1.0 µm and 3.0 µm on the wall behind the heat sources. These findings are juxtaposed with the pattern of particles with varying sizes situated above the single near-wall heat source and away from the heat sources. The study delves into the impact of varying surface temperatures and the distance from the wall behind the heat sources, as well as the top surface of the heat source, on particle deposition in 29 distinct cases. The results indicate that the deposition velocity of particles with the same size is highest above the adjacent near-wall heat sources, followed by that of a single near-wall heat source, and finally, locations away from the near-wall heat source. Also, the decay rate loss coefficient of particles with the same size above the adjacent near-wall heat sources increases with a decrease in the distance of the heat sources from the wall behind them, an increase in the temperature of the heat sources, and a reduction in distance from the top surface of heat sources.

20.
Front Psychiatry ; 15: 1395198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690204

RESUMO

Aim: Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT. Methods: We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains. Results: As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains. Conclusion: Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...