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1.
Mol Cell ; 72(6): 1021-1034.e4, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30472193

RESUMO

The dynamic transcriptional regulation and interactions of human germlines and surrounding somatic cells during folliculogenesis remain unknown. Using RNA sequencing (RNA-seq) analysis of human oocytes and corresponding granulosa cells (GCs) spanning five follicular stages, we revealed unique features in transcriptional machinery, transcription factor networks, and reciprocal interactions in human oocytes and GCs that displayed developmental-stage-specific expression patterns. Notably, we identified specific gene signatures of two cell types in particular developmental stage that may reflect developmental competency and ovarian reserve. Additionally, we uncovered key pathways that may concert germline-somatic interactions and drive the transition of primordial-to-primary follicle, which represents follicle activation. Thus, our work provides key insights into the crucial features of the transcriptional regulation in the stepwise folliculogenesis and offers important clues for improving follicle recruitment in vivo and restoring fully competent oocytes in vitro.


Assuntos
Comunicação Celular/genética , Células da Granulosa/fisiologia , Oócitos/fisiologia , Folículo Ovariano/fisiologia , Reserva Ovariana/genética , Transcriptoma , Adulto , Animais , Biologia Computacional , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Humanos , Camundongos , Folículo Ovariano/citologia , Transdução de Sinais/genética , Análise de Célula Única , Especificidade da Espécie , Transcrição Gênica , Adulto Jovem
2.
J Biol Chem ; 299(11): 105281, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37742921

RESUMO

Skeletal muscle consists of different muscle fiber types whose heterogeneity is characterized by different metabolic patterns and expression of MyHC isomers. The transformation of muscle fiber types is regulated by a complex molecular network in which long noncoding (lnc) RNAs play an important role. In this study, we found that lnc-H19 is more enriched in slow muscle fibers. In vitro, interference of lnc-H19 by siRNA significantly promoted the expression of fast muscle fiber gene MyHC IIB and inhibited the expression of the slow muscle fiber gene MyHC I, thereby leading to a fast muscle fiber phenotype. In addition, interference of lnc-H19 significantly inhibited mRNA expression of the mitochondrial genes, such as COX5A, COX-2, UQCRFSL, FABP3, and CD36. Overexpression of lnc-H19 resulted in an opposite result. In vivo, knockdown of lnc-H19 by AAV-shRNA-H19 suppressed the mRNA expression of the slow muscle fiber gene MyHC I and the protein expression of slow-MyHC. Simultaneously, mitochondria were reduced in number, swollen, and vacuolated. The activities of succinate dehydrogenase, lactic dehydrogenase, and superoxide dismutase were significantly inhibited, and malondialdehyde content was significantly increased, indicating that deficiency of lnc-H19 leads to decreased oxidative metabolism and antioxidant capacity in muscle. Furthermore, inhibition of lnc-H19 decreased the weight-bearing swimming time and limb suspension time of mice. In conclusion, our results revealed the role of lnc-H19 in maintaining slow muscle fiber types and maintaining exercise endurance, which may help to further improve the regulatory network of lnc-H19 in muscle function.


Assuntos
RNA Longo não Codificante , Animais , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Masculino , Linhagem Celular , Camundongos Endogâmicos C57BL
3.
Glob Chang Biol ; 30(4): e17291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38647225

RESUMO

Terrestrial ecosystem resilience is crucial for maintaining the structural and functional stability of ecosystems following disturbances. However, changes in resilience over the past few decades and the risk of future resilience loss under ongoing climate change are unclear. Here, we identified resilience trends using two remotely sensed vegetation indices, analyzed the relative importance of potential driving factors to resilience changes, and finally assessed the risk of future resilience loss based on the output data of eight models from CMIP6. The results revealed that more than 60% of the ecosystems experienced a conversion from an increased trend to a declined trend in resilience. Attribution analysis showed that the most important driving factors of declined resilience varied regionally. The declined trends in resilience were associated with increased precipitation variability in the tropics, decreased vegetation cover in arid region, increased temperature variability in temperate regions, and increased average temperature in cold regions. CMIP6 reveals that terrestrial ecosystems under SPP585 are expected to experience more intense declines in resilience than those under SSP126 and SSP245, particularly in cold regions. These results highlight the risk of continued degradation of ecosystem resilience in the future and the urgency of climate mitigation actions.


Assuntos
Mudança Climática , Ecossistema , Temperatura , Modelos Teóricos
4.
Reprod Biol Endocrinol ; 22(1): 37, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576003

RESUMO

Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.


Assuntos
Endométrio , Selectina L , Gravidez , Humanos , Masculino , Feminino , Proteína Beclina-1 , Selectina L/metabolismo , Endométrio/metabolismo , Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/metabolismo , Implantação do Embrião/fisiologia , Autofagia , Células Estromais/metabolismo , Apoptose
5.
Am J Obstet Gynecol ; 230(4): 436.e1-436.e12, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135094

RESUMO

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.


Assuntos
Aborto Espontâneo , COVID-19 , Gravidez , Humanos , Masculino , Feminino , Resultado da Gravidez , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos Prospectivos , COVID-19/terapia , COVID-19/etiologia , SARS-CoV-2 , Sêmen , Fertilização in vitro/efeitos adversos , Transferência Embrionária , Taxa de Gravidez , Estudos Retrospectivos
6.
EMBO Rep ; 23(8): e54438, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35735238

RESUMO

Mixed lineage kinase domain-like protein (MLKL) is the terminal effector of necroptosis, a form of regulated necrosis. Optimal activation of necroptosis, which eliminates infected cells, is critical for antiviral host defense. MicroRNAs (miRNAs) regulate the expression of genes involved in various biological and pathological processes. However, the roles of miRNAs in necroptosis-associated host defense remain largely unknown. We screened a library of miRNAs and identified miR-324-5p as the most effective suppressor of necroptosis. MiR-324-5p downregulates human MLKL expression by specifically targeting the 3'UTR in a seed region-independent manner. In response to interferons (IFNs), miR-324-5p is downregulated via the JAK/STAT signaling pathway, which removes the posttranscriptional suppression of MLKL mRNA and facilitates the activation of necroptosis. In influenza A virus (IAV)-infected human primary macrophages, IFNs are induced, leading to the downregulation of miR-324-5p. MiR-324-5p overexpression attenuates IAV-associated necroptosis and enhances viral replication, whereas deletion of miR-324-5p potentiates necroptosis and suppresses viral replication. Hence, miR-324-5p negatively regulates necroptosis by manipulating MLKL expression, and its downregulation by IFNs orchestrates optimal activation of necroptosis in host antiviral defense.


Assuntos
Vírus da Influenza A , MicroRNAs , Antivirais , Humanos , Interferons , MicroRNAs/genética , MicroRNAs/metabolismo , Necroptose , Replicação Viral/fisiologia
7.
J Org Chem ; 89(5): 3635-3643, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359465

RESUMO

The development and utilization of new dienes and dienophiles for the controlled synthesis of isoquinuclidines is highly appealing. Herein, we describe a novel strategy for diastereoselective synthesis of indoline-fused isoquinuclidines via copper-catalyzed dearomative Diels-Alder reaction of cyclic amidines with indoles. This protocol avoids the use of unstable DHPs and activated alkenes, offering a more efficient and selective approach to synthesize isoquinuclidines.

8.
Mol Biol Rep ; 51(1): 359, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400863

RESUMO

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.


Assuntos
Endometriose , Sirolimo , Animais , Feminino , Humanos , Sirolimo/uso terapêutico , Endométrio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Proteínas Serina-Treonina Quinases/metabolismo , Mamíferos/metabolismo , Endometriose/metabolismo
9.
Macromol Rapid Commun ; 45(9): e2300685, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38339795

RESUMO

The air filtration materials with high efficiency, low resistance, and extra antibacterial property are crucial for personal health protection. Herein, a tree-like polyvinylidene fluoride (PVDF) nanofibrous membrane with hierarchical structure (trunk fiber of 447 nm, branched fiber of 24.7 nm) and high filtration capacity is demonstrated. Specifically, 2-hydroxypropyl trimethyl ammonium chloride terminated hyperbranched polymer (HBP-HTC) with near-spherical three-dimensional molecular structure and adjustable terminal positive groups is synthesized as an additive for PVDF electrospinning to enhance the jet splitting and promote the formation of branched ultrafine nanofibers, achieving a coverage rate of branched nanofibers over 90% that is superior than small molecular quaternary ammonium salts. The branched nanofibers network enhances mechanical properties and filtration efficiency (99.995% for 0.26 µm sodium chloride particles) of the PVDF/HBP-HTC membrane, which demonstrates reduced pressure drop (122.4 Pa) and a quality factor up to 0.083 Pa-1 on a 40 µm-thick sample. More importantly, the numerous quaternary ammonium salt groups of HBP-HTC deliver excellent antibacterial properties to the PVDF membranes. Bacterial inhibitive rate of 99.9% against both S. aureus and E. coli is demonstrated in a membrane with 3.0 wt% HBP-HTC. This work provides a new strategy for development of high-efficiency and antibacterial protection products.


Assuntos
Antibacterianos , Escherichia coli , Nanofibras , Polímeros , Polivinil , Staphylococcus aureus , Nanofibras/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Polivinil/química , Polímeros/química , Polímeros/farmacologia , Polímeros/síntese química , Membranas Artificiais , Testes de Sensibilidade Microbiana , Filtros de Ar , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Filtração/métodos , Tamanho da Partícula , Polímeros de Fluorcarboneto
10.
Acta Pharmacol Sin ; 45(1): 180-192, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37644132

RESUMO

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Camundongos , Animais , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Moléculas de Adesão Celular , Progressão da Doença , Linhagem Celular Tumoral
11.
Acta Pharmacol Sin ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914677

RESUMO

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

12.
Cereb Cortex ; 33(18): 10013-10027, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37557907

RESUMO

We investigated the neurocognitive mechanisms underlying the processing of combinatorial unstated meaning. Sentences like "Charles jumped for 5 minutes." engender an iterative meaning that is not explicitly stated but enriched by comprehenders beyond simple composition. Comprehending unstated meaning involves meaning contextualization-integrative meaning search in sentential-discourse context. Meanwhile, people differ in how they process information with varying context sensitivity. We hypothesized that unstated meaning processing would vary with individual socio-cognitive propensity indexed by the Autism-Spectrum Quotient (AQ), accompanied by differential cortical engagements. Using functional magnetic resonance imaging, we examined the processing of sentences with unstated iterative meaning in typically-developed individuals and found an engagement of the fronto-parietal network, including the left pars triangularis (L.PT), right intraparietal (R.IPS), and parieto-occipital sulcus (R.POS). We suggest that the L.PT subserves a contextual meaning search, while the R.IPS/POS supports enriching unstated iteration in consideration of event durations and interval lengths. Moreover, the activation level of these regions negatively correlated with AQ. Higher AQ ties to lower L.PT activation, likely reflecting weaker context sensitivity, along with lower IPS activation, likely reflecting weaker computation of events' numerical-temporal specifications. These suggest that the L.PT and R.IPS/POS support the processing of combinatorial unstated meaning, with the activation level modulated by individual cognitive styles.


Assuntos
Encéfalo , Pensamento , Humanos , Encéfalo/fisiologia , Idioma , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cognição , Semântica , Mapeamento Encefálico
13.
Tob Control ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38458757

RESUMO

OBJECTIVES: To examine the associations between tobacco industry denormalisation (TID) beliefs and support for tobacco endgame policies. METHODS: A total of 2810 randomly selected adult respondents of population-based tobacco policy-related surveys (2018-2019) were included. TID beliefs (agree vs disagree/unsure) were measured by seven items: tobacco manufacturers ignore health, induce addiction, hide harm, spread false information, lure smoking, interfere with tobacco control policies and should be responsible for health problems. Score of each item was summed up and dichotomised (median=5, >5 strong beliefs; ≤5 weak beliefs). Support for tobacco endgame policies on total bans of tobacco sales (yes/no) and use (yes/no) was reported. Associations between TID beliefs and tobacco endgame policies support across various smoking status were analysed, adjusting for sociodemographics. RESULTS: Fewer smokers (23.3%) had strong beliefs of TID than ex-smokers (48.4%) and never smokers (48.5%) (p<0.001). Support for total bans on tobacco sales (74.6%) and use (76.9%) was lower in smokers (33.3% and 35.3%) than ex-smokers (74.3% and 77.9%) and never smokers (76.0% and 78.3%) (all p values<0.001). An increase in the number of TID beliefs supported was positively associated with support for a total ban on sales (adjusted risk ratio 1.06, 95% CI 1.05 to 1.08, p<0.001) and use (1.06, 95% CI 1.05 to 1.07, p<0.001). The corresponding associations were stronger in smokers than non-smokers (sales: 1.87 vs 1.25, p value for interaction=0.03; use: 1.78 vs 1.21, p value for interaction=0.03). CONCLUSION: Stronger TID belief was associated with greater support for total bans on tobacco sales and use. TID intervention may increase support for tobacco endgame, especially in current smokers.

14.
Nephrology (Carlton) ; 29(7): 383-393, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38373789

RESUMO

AIM: This study aimed to establish a prediction model in peritoneal dialysis patients to estimate the risk of technique failure and guide clinical practice. METHODS: Clinical and laboratory data of 424 adult peritoneal dialysis patients were retrospectively collected. The risk prediction models were built using univariate Cox regression, best subsets approach and LASSO Cox regression. Final nomogram was constructed based on the best model selected by the area under the curve. RESULTS: After comparing three models, the nomogram was built using the LASSO Cox regression model. This model included variables consisting of hypertension and peritonitis, serum creatinine, low-density lipoprotein, fibrinogen and thrombin time, and low red blood cell count, serum albumin, triglyceride and prothrombin activity. The predictive model constructed performed well using receiver operating characteristic curve and area under the curve value, C-index and calibration curve. CONCLUSION: This study developed and verified a new prediction instrument for the risk of technique failure among peritoneal dialysis patients.


Assuntos
Nomogramas , Diálise Peritoneal , Humanos , Diálise Peritoneal/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos , Falha de Tratamento , Fatores de Risco , Idoso , Adulto , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Valor Preditivo dos Testes , Curva ROC
15.
Postgrad Med J ; 100(1184): 373-381, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38211949

RESUMO

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Imunoterapia , Instabilidade de Microssatélites , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Mutação
16.
J Med Internet Res ; 26: e44973, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739429

RESUMO

BACKGROUND: While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. OBJECTIVE: This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. METHODS: From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. RESULTS: Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). CONCLUSIONS: An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.


Assuntos
Aplicativos Móveis , Abandono do Hábito de Fumar , Envio de Mensagens de Texto , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hong Kong , Smartphone , Fumantes/psicologia , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia
17.
J Dairy Sci ; 107(6): 3400-3412, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38135045

RESUMO

Hypothyroidism has been found to have an effect on the nutritional composition of human milk during pregnancy. This study aims to explore the combined influence of rheological properties, macronutrient content, particle size, and the zeta potential of milk fat globules, as well as the composition of milk fat globule membrane (MFGM) proteins on the quality of human milk in gestational hypothyroidism. The study revealed that human milk from the group with hypothyroidism during pregnancy (AHM) was less viscoelastic and stable when compared with normal pregnancy group human milk (NHM). Furthermore, the particle size and macronutrient content of NHM were found to be larger than that of AHM. In contrast, the zeta potential of AHM was greater than that of NHM. The sodium dodecyl sulfate-PAGE results disclosed that the composition of MFGM proteins in these 2 groups were generally the same, but the content of AHM was lower than that of NHM. In conclusion, this study confirms that hypothyroidism during pregnancy can have a significant effect on the quality of human milk.


Assuntos
Hipotireoidismo , Leite Humano , Reologia , Feminino , Humanos , Gravidez , Leite Humano/química , Hipotireoidismo/veterinária , Glicolipídeos
18.
J Adv Nurs ; 80(7): 2813-2821, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38482900

RESUMO

AIM: To measure the association of leader-member exchange and team-member exchange with nurses' innovative behaviours through social exchange theory. BACKGROUND: The field of nursing is actively advocating innovation. Other fields have proven that leader-member exchange and team-member exchange can promote innovative behaviour, but such an association is not clear in nursing. DESIGN: A cross-sectional study. METHODS: A total of 560 nurses were selected from five tertiary hospitals in Henan Province (China) by multistage sampling. Data were collected from a self-report questionnaire. Thirty nurses in the pre-survey were used to verify the validity of the questionnaire. SPSS PROCESS macro was used to verify the association of leader-member exchange and team-member exchange with nurses' innovative behaviours. RESULTS: Leader-member exchange and team-member exchange were significantly associated with nurses' innovative behaviours, and team-member exchange had a mediating effect on the relationship between leader-member exchange and innovative behaviour. CONCLUSIONS: Leader-member exchange and team-member exchange positively affect nurses' innovative behaviours. Leader-member exchange can promote nurses' innovative behaviours through the mediating role of team-member exchange. IMPACT: This study indicated that leader-member exchange and team-member exchange should be given more attention in promoting nurses' innovative behaviours. This finding has implications for the promotion of innovative behaviours in nurses. Leaders need to focus on the innovative needs of nurses and offer support. Meanwhile, leadership training programs are necessary for managers to create positive team relationships. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.


Assuntos
Liderança , Recursos Humanos de Enfermagem Hospitalar , Humanos , Estudos Transversais , Adulto , Feminino , Masculino , China , Inquéritos e Questionários , Recursos Humanos de Enfermagem Hospitalar/psicologia , Relações Interprofissionais , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde
19.
J Environ Manage ; 351: 119963, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169261

RESUMO

Ecological restoration projects in the Tibetan Plateau aimed to reverse ecosystem degradation and safeguard the fragile alpine ecological environment. However, it is still being determined if the vegetation restoration is successful on a large scale or reaches the expected magnitude, restricting our ability to adapt practices to maximise the benefit. With multiple vegetation indices (VIs: NDVI, LAI, and GPP) from satellite observations and random forest machine-learning models, we performed an attribution study on vegetation growth trends caused by climate change and human activities. Then, we further explored the relationship between vegetation growth and ecological projects and human footprint without the influence of climate. The results showed that climatic change was a relatively strong driver of vegetation growth. The positive contributions of ecological restoration occurred only in half of the plateau due to the increased human footprint. Vegetation enhancement resulting from ecological restoration occurred in 13.1%-23.1% of the plateau. Among these values, ecological restoration counteracted the negative climate effects in 4.7%-8.3% of the plateau (about half of the negative climate effect area). In forest and grassland protection areas, the ecological restoration was more successful. The study provides a better understanding of the role of ecological projects in vegetation restoration and potential threats to its effectiveness. This is essential to improve future restoration projects.


Assuntos
Ecossistema , Meio Ambiente , Humanos , Tibet , Temperatura , Mudança Climática , China
20.
Medicina (Kaunas) ; 60(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38792963

RESUMO

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein-protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Conexina 43 , Neoplasias Renais , Humanos , Conexina 43/análise , Conexina 43/metabolismo , Neoplasias Renais/genética , Biomarcadores Tumorais/análise , Prognóstico , beta Catenina , Linhagem Celular Tumoral , Masculino , Feminino
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