Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 786
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 187(21): 6055-6070.e22, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39181133

RESUMO

Chromothripsis describes the catastrophic shattering of mis-segregated chromosomes trapped within micronuclei. Although micronuclei accumulate DNA double-strand breaks and replication defects throughout interphase, how chromosomes undergo shattering remains unresolved. Using CRISPR-Cas9 screens, we identify a non-canonical role of the Fanconi anemia (FA) pathway as a driver of chromothripsis. Inactivation of the FA pathway suppresses chromosome shattering during mitosis without impacting interphase-associated defects within micronuclei. Mono-ubiquitination of FANCI-FANCD2 by the FA core complex promotes its mitotic engagement with under-replicated micronuclear chromosomes. The structure-selective SLX4-XPF-ERCC1 endonuclease subsequently induces large-scale nucleolytic cleavage of persistent DNA replication intermediates, which stimulates POLD3-dependent mitotic DNA synthesis to prime shattered fragments for reassembly in the ensuing cell cycle. Notably, FA-pathway-induced chromothripsis generates complex genomic rearrangements and extrachromosomal DNA that confer acquired resistance to anti-cancer therapies. Our findings demonstrate how pathological activation of a central DNA repair mechanism paradoxically triggers cancer genome evolution through chromothripsis.


Assuntos
Cromotripsia , Resistencia a Medicamentos Antineoplásicos , Anemia de Fanconi , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Anemia de Fanconi/metabolismo , Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Mitose , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Sistemas CRISPR-Cas/genética , Replicação do DNA , Recombinases/metabolismo , Reparo do DNA , Linhagem Celular Tumoral , Endonucleases/metabolismo , Endonucleases/genética , Quebras de DNA de Cadeia Dupla , Animais , Camundongos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ubiquitinação
2.
Nature ; 618(7967): 1041-1048, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37165191

RESUMO

Complex genome rearrangements can be generated by the catastrophic pulverization of missegregated chromosomes trapped within micronuclei through a process known as chromothripsis1-5. As each chromosome contains a single centromere, it remains unclear how acentric fragments derived from shattered chromosomes are inherited between daughter cells during mitosis6. Here we tracked micronucleated chromosomes with live-cell imaging and show that acentric fragments cluster in close spatial proximity throughout mitosis for asymmetric inheritance by a single daughter cell. Mechanistically, the CIP2A-TOPBP1 complex prematurely associates with DNA lesions within ruptured micronuclei during interphase, which poises pulverized chromosomes for clustering upon mitotic entry. Inactivation of CIP2A-TOPBP1 caused acentric fragments to disperse throughout the mitotic cytoplasm, stochastically partition into the nucleus of both daughter cells and aberrantly misaccumulate as cytoplasmic DNA. Mitotic clustering facilitates the reassembly of acentric fragments into rearranged chromosomes lacking the extensive DNA copy-number losses that are characteristic of canonical chromothripsis. Comprehensive analysis of pan-cancer genomes revealed clusters of DNA copy-number-neutral rearrangements-termed balanced chromothripsis-across diverse tumour types resulting in the acquisition of known cancer driver events. Thus, distinct patterns of chromothripsis can be explained by the spatial clustering of pulverized chromosomes from micronuclei.


Assuntos
Cromossomos Humanos , Cromotripsia , Micronúcleos com Defeito Cromossômico , Mitose , Humanos , Centrômero , Cromossomos Humanos/genética , DNA/genética , DNA/metabolismo , Variações do Número de Cópias de DNA , Interfase , Mitose/genética , Neoplasias/genética
3.
Plant Physiol ; 195(4): 3053-3071, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38717740

RESUMO

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.


Assuntos
Ácido Abscísico , Secas , Regulação da Expressão Gênica de Plantas , Glycine max , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Glycine max/genética , Glycine max/fisiologia , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Transdução de Sinais/genética
4.
Chem Soc Rev ; 53(20): 9964-9975, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39269194

RESUMO

Currently, most catalysts used for photoconverting carbon dioxide (CO2) typically produce C1 products. Achieving multicarbon (C2+) products, which are highly desirable due to their greater energy density and economic potential, still remains a significant challenge. This difficulty is primarily due to the kinetic hurdles associated with the C-C coupling step in the process. Given this, devising diverse strategies to accelerate C-C coupling for generating multicarbon products is requisite. Herein, we first give a classification of catalysts involved in the photoconversion of CO2 to C2+ fuels. We summarize metallic oxides, metallic sulfides, MXenes, and metal-organic frameworks as catalysts for CO2 photoreduction to C2+ products, attributing their efficacy to the inherent dual active sites facilitating C-C coupling. In addition, we survey covalent organic frameworks, carbon nitrides, metal phosphides, and graphene as cocatalysts for CO2 photoreduction to C2+ products, owing to the incorporated dual active sites that induce C-C coupling. In the end, we provide a brief conclusion and an outlook on designing new photocatalysts, understanding the catalytic mechanisms, and considering the practical application requirements for photoconverting CO2 into multicarbon products.

5.
Semin Cell Dev Biol ; 123: 100-109, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33824062

RESUMO

Cancer genomes frequently harbor structural chromosomal rearrangements that disrupt the linear DNA sequence order and copy number. To date, diverse classes of structural variants have been identified across multiple cancer types. These aberrations span a wide spectrum of complexity, ranging from simple translocations to intricate patterns of rearrangements involving multiple chromosomes. Although most somatic rearrangements are acquired gradually throughout tumorigenesis, recent interrogation of cancer genomes have uncovered novel categories of complex rearrangements that arises rapidly through a one-off catastrophic event, including chromothripsis and chromoplexy. Here we review the cellular and molecular mechanisms contributing to the formation of diverse structural rearrangement classes during cancer development. Genotoxic stress from a myriad of extrinsic and intrinsic sources can trigger DNA double-strand breaks that are subjected to DNA repair with potentially mutagenic outcomes. We also highlight how aberrant nuclear structures generated through mitotic cell division errors, such as rupture-prone micronuclei and chromosome bridges, can instigate massive DNA damage and the formation of complex rearrangements in cancer genomes.


Assuntos
Cromotripsia , Neoplasias , Aberrações Cromossômicas , Rearranjo Gênico/genética , Genoma , Humanos , Neoplasias/genética
6.
J Gen Virol ; 105(4)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38602389

RESUMO

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.


Assuntos
Hemípteros , Orthobunyavirus , Vírus de RNA , Animais , Feminino , Filogenia , Insetos , Vírus de RNA/genética
7.
Small ; 20(25): e2310180, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38342676

RESUMO

Knee replacement surgery confronts challenges including patient dissatisfaction and the necessity for secondary procedures. A key requirement lies in dual-modal measurement of force and temperature of artificial joints during postoperative monitoring. Here, a novel non-toxic near-infrared (NIR) phosphor Sr3Sn2O7:Nd, Yb, is designed to realize the dual-modal measurement. The strategy is to entail phonon-assisted upconversion luminescence (UCL) and trap-controlled mechanoluminescence (ML) in a single phosphor well within the NIR biological transmission window. The phosphor is embedded in medical bone cement forming a smart joint in total knee replacements illustrated as a proof-of-concept. The sensing device can be charged in vitro by a commercial X-ray source with a safe dose rate for ML, and excited by a low power 980 nm laser for UCL. It attains impressive force and temperature sensing capabilities, exhibiting a force resolution of 0.5% per 10 N, force detection threshold of 15 N, and a relative temperature sensitive of up to 1.3% K-1 at 309 K. The stability against humidity and thermal shock together with the robustness of the device are attested. This work introduces a novel methodological paradigm, paving the way for innovative research to enhance the functionality of artificial tissues and joints in living organisms.


Assuntos
Artroplastia do Joelho , Temperatura , Humanos , Estrôncio/química , Itérbio/química , Luminescência , Neodímio/química , Medições Luminescentes/métodos , Raios Infravermelhos
8.
Planta ; 259(4): 76, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418674

RESUMO

MAIN CONCLUSION: Investigation the expression patterns of GmPT genes in response to various abiotic stresses and overexpression of GmPT11 in soybean hairy roots and Arabidopsis exhibited hypersensitivity to salt stress. Soybean is considered to be one of the significant oil crops globally, as it offers a diverse range of essential nutrients that contribute to human health. Salt stress seriously affects the yield of soybean through negative impacts on the growth, nodulation, reproduction, and other agronomy traits. The phosphate transporters 1(PHT1) subfamily, which is a part of the PHTs family in plants, is primarily found in the cell membrane and responsible for the uptake and transport of phosphorus. However, the role of GmPT (GmPT1-GmPT14) genes in response to salt stress has not been comprehensively studied. Here, we conducted a systematic analysis to ascertain the distribution and genomic duplications of GmPT genes, as well as their expression patterns in response to various abiotic stresses. Promoter analysis of GmPT genes revealed that six stress-related cis-elements were enriched in these genes. The overexpression of GmPT11 in soybean hairy roots and Arabidopsis exhibited hypersensitivity to salt stress, while no significant change was observed under low phosphate treatment, suggesting a crucial role in the response to salt stress. These findings provide novel insights into enhancing plant tolerance to salt stress.


Assuntos
Arabidopsis , Glycine max , Humanos , Glycine max/genética , Arabidopsis/genética , Estresse Fisiológico/genética , Estresse Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
9.
Histochem Cell Biol ; 161(2): 195-205, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37874337

RESUMO

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-ß/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.


Assuntos
Prolapso de Órgão Pélvico , Qualidade de Vida , Feminino , Humanos , Transdução de Sinais , Prolapso de Órgão Pélvico/metabolismo , Prolapso de Órgão Pélvico/patologia , Vagina/metabolismo , Vagina/patologia , Luciferases/metabolismo
10.
Toxicol Appl Pharmacol ; 487: 116960, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735592

RESUMO

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.


Assuntos
Apoptose , Neoplasias Colorretais , Sistema de Sinalização das MAP Quinases , Xilulose , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Xilulose/farmacologia , Xilulose/metabolismo , Masculino , Animais , Feminino , Proliferação de Células/efeitos dos fármacos , Fezes/química , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Células HT29 , Idoso
11.
J Theor Biol ; 577: 111673, 2024 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-37984586

RESUMO

One of the most significant challenges in biology is to elucidate the roles of various regulatory interactions in cell fate decision and transition. However, it remains to be fully clarified how they cooperate and determine fate transition. Here, a general framework based on statistical analysis and bifurcation theory is proposed to identify crucial regulatory interactions and how they play decisive roles in fate transition. More exactly, specific feedback loops determine occurrence of bifurcations by which cell fate transition can be realized. While regulatory interactions in the feedback loops determine the direction of transition. In addition, two-parameter bifurcation analysis further provides detailed understanding of how the fate transition based on statistical analysis occurs. Statistical analysis can also be used to reveal synergistic combinatorial perturbations by which fate transition can be more efficiently realized. The integrative analysis approach can be used to identify critical regulatory interactions in cell fate transition and reveal how specific cell fate transition occurs. To verify feasibility of the approach, the epithelial to mesenchymal transition (EMT) network is chosen as an illustrative example. In agreement with experimental observations, the approach reveals some critical regulatory interactions and underlying mechanisms in cell fate determination and transitions between three states. The approach can also be applied to analyze other regulatory networks related to cell fate decision and transition.


Assuntos
Transição Epitelial-Mesenquimal , Redes Reguladoras de Genes , Diferenciação Celular , Retroalimentação
12.
J Org Chem ; 89(19): 13868-13875, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39294860

RESUMO

A novel reaction of cyclic and acyclic secondary amines with in situ-generated allene intermediate species from nitro-substituted donor-acceptor cyclopropanes is reported. In the presence of a simple inorganic base, NaOH, tetrasubstituted enamine derivatives can be obtained in moderate to excellent yields. The reaction is operationally easy, features mild reaction conditions and simple inorganic bases, and is free of transition metals.

13.
Acta Pharmacol Sin ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384887

RESUMO

p53, a tumor suppressor protein, has a vital role in the regulation of the cell cycle, apoptosis, and DNA damage repair. The degradation of p53 is predominantly controlled by the murine double minute 2 (MDM2) protein, a ubiquitin E3 ligase. The overexpression or amplification of MDM2 is commonly observed in various human cancers bearing wild-type p53 alleles, leading to the rapid degradation of the p53 protein and the attenuation of p53 tumor suppression functions. Thus, a major effort in p53-based cancer therapy has been to research MDM2 antagonists that specifically stabilize and activate p53, leading to the suppression of tumor growth. However, despite numerous efforts to develop MDM2 antagonists, to date they have failed to reach clinical use, largely because of the cytotoxicity associated with these small molecules. This study used our newly designed structure-based virtual screening approach on a commercial compound library to identify a novel compound, CGMA-Q18, which directly binds to MDM2, leading to the activation of p53, the induction of apoptosis, and cell cycle arrest in cancer cells. Notably, CGMA-Q18 significantly inhibited tumor xenograft growth in nude mice without observable toxicity. These findings highlight our useful virtual screening protocol and CGMA-Q18 as a putative MDM2 antagonist.

14.
Acta Pharmacol Sin ; 45(9): 1964-1977, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38698214

RESUMO

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.


Assuntos
Antineoplásicos , Proliferação de Células , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Neoplasias da Próstata , Quinolinas , Masculino , Animais , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Quinolinas/farmacologia , Quinolinas/química , Quinolinas/uso terapêutico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Agonismo Inverso de Drogas , Camundongos , Camundongos Nus , Descoberta de Drogas , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C
15.
BMC Pregnancy Childbirth ; 24(1): 391, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807069

RESUMO

BACKGROUND: The worldwide occurrence of triplet pregnancy is estimated to be 0.093%, with a natural incidence of approximately 1 in 8000. This study aims to analyze the neonatal health status and birth weight discordance (BWD) of triplets based on chorionicity from birth until discharge. METHODS: This was a retrospective study. We reviewed a total of 136 triplet pregnancies at our tertiary hospital between January 1, 2001, and December 31, 2021. Maternal and neonatal outcomes, inter-triplet BWD, neonatal morbidity, and mortality were analyzed. RESULTS: Among all cases, the rates of intrauterine death, neonatal death, and perinatal death were 10.29, 13.07, and 24.26%, respectively. Thirty-seven of the cases resulted in fetal loss, including 13 with fetal anomalies. The maternal complications and neonatal outcomes of the 99 triplet pregnancies without fetal loss were compared across different chorionicities, including a dichorionic (DC) group (41 cases), trichorionic (TC) group (37 cases), and monochorionic (MC) group (21 cases). Neonatal hypoproteinemia (P < 0.001), hyperbilirubinemia (P < 0.019), and anemia (P < 0.003) exhibited significant differences according to chorionicity, as did the distribution of BWD (P < 0.001). More than half of the cases in the DC and TC groups had a BWD < 15%, while those in the MC group had a BWD < 50% (47.6%). TC pregnancy decreased the risk of neonatal anemia (adjusted odds ratio [AOR] = 0.084) and need for blood transfusion therapy after birth (AOR = 0.119). In contrast, a BWD > 25% increased the risk of neonatal anemia (AOR = 10.135) and need for blood transfusion after birth (AOR = 7.127). TC pregnancy, MCDA or MCTA, and BWD > 25% increased neonatal hypoproteinemia, with AORs of 4.629, 5.123, and 5.343, respectively. CONCLUSIONS: The BWD differed significantly according to chorionicity. Additionally, TC pregnancies reduced the risk of neonatal anemia and need for blood transfusion, but increased the risk of neonatal hypoproteinemia. In contrast, the BWD between the largest and smallest triplets increased the risk of neonatal anemia and the need for blood transfusion. TC pregnancy, MCDA or MCTA, and BWD > 25% increased the risks of neonatal hypoproteinemia. However, due to the limited number of triplet pregnancies, further exploration of the underlying mechanism is warranted.


Assuntos
Córion , Resultado da Gravidez , Gravidez de Trigêmeos , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Recém-Nascido , Adulto , Resultado da Gravidez/epidemiologia , Peso ao Nascer , Trigêmeos , Morte Fetal/etiologia
16.
Lipids Health Dis ; 23(1): 6, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38185620

RESUMO

BACKGROUND: Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography-mass spectrometry (GC-MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC-MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis. METHODS: The established in situ derivatization method for analysing LCFAs with a GC-MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out (Tcrd-/-) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients. RESULTS: A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC-MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd-/- mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly. CONCLUSIONS: This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd-/- mice.


Assuntos
Interleucina-17 , Psoríase , Humanos , Animais , Camundongos , Interleucina-17/genética , Cromatografia Gasosa-Espectrometria de Massas , Lipidômica , Psoríase/tratamento farmacológico , Ácidos Graxos , Ácidos Graxos Monoinsaturados , Imiquimode , Anticorpos Monoclonais/uso terapêutico
17.
BMC Public Health ; 24(1): 365, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310254

RESUMO

BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Depressão/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Adesão à Medicação , Comportamento Sexual , Ansiedade/epidemiologia , China/epidemiologia
18.
Arch Gynecol Obstet ; 310(2): 1027-1035, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38431699

RESUMO

INTRODUCTION: Pregnant women with pre-excitation syndrome are more likely to develop supraventricular tachycardia (SVT) during pregnancy and delivery, leading to an increased risk of adverse events. METHOD: This was a retrospective study of 309 pregnancies in 280 women (29 women had two pregnancies in this series) with pre-excitation syndrome who delivered at West China Second University Hospital from June 2011 to October 2021. All the 309 pregnant women with pre-excitation syndrome were divided into SVT and non-SVT groups to analyze the cardiac and obstetric complications. RESULTS: Among the included pregnant women in the past 10 years, the prevalence of pre-excitation syndrome was 0.24% (309/127725). There were 309 cases with pre-excitation syndrome in all hospitalized pregnant women. Among them, 62 (20.1%, 62/309) had a history of SVT. In the 62 cases with SVT during pregnancy, 22 (35.5%) cases had a history of SVT. Gestational diabetes mellitus was associated with SVT during pregnancy. The cesarean section rate was 88.7% in the SVT group, which was significantly higher than that in the non-SVT group (64.8%) (P < 0.001). Cases with SVT during pregnancy had more cardiac and obstetric complications. Four fetal deaths were recorded in the SVT group. Additionally, 29 women experienced two pregnancies during the study period, among whom, five received radiofrequency ablation after the first delivery and obtained better outcomes in the second pregnancy. CONCLUSION: The adverse outcomes such as cardiac complications, maternal and fetal complications (PROM, prematurity, SGA, fetal distress, etc.) in pregnant women with pre-excitation syndrome were closely related to SVT, with possible risk factors including history of SVT before pregnancy, cardiac function, heart organic abnormalities, and gestational diabetes mellitus.


Assuntos
Cesárea , Diabetes Gestacional , Síndromes de Pré-Excitação , Resultado da Gravidez , Taquicardia Supraventricular , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Resultado da Gravidez/epidemiologia , Síndromes de Pré-Excitação/epidemiologia , Síndromes de Pré-Excitação/complicações , China/epidemiologia , Taquicardia Supraventricular/epidemiologia , Taquicardia Supraventricular/etiologia , Cesárea/estatística & dados numéricos , Diabetes Gestacional/epidemiologia , Complicações Cardiovasculares na Gravidez/epidemiologia , Adulto Jovem
19.
Arch Gynecol Obstet ; 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39432056

RESUMO

OBJECTIVE: Selective termination (ST) is an appropriate procedure for managing discordant fetal anomalies in dichorionic diamniotic (DCDA) twin pregnancies. The aim of this study was to investigate the perinatal outcomes of ST at different gestational ages in DCDA twin pregnancies. METHODS: This retrospective study was conducted on DCDA twin pregnancies with STs at West China Second University Hospital between January 2012 and December 2022. According to the gestational age at which ST was performed, the patients were assigned to four groups: Group 1 (13 to 17 + 6 weeks), Group 2 (18 to 23 + 6 weeks), Group 3 (24 to 27 + 6 weeks), and Group 4 (≥ 28 weeks). RESULTS: We identified 230 patients for this study. The overall rates of miscarriage, preterm delivery at < 32 weeks, and term delivery were 1.3%, 10.5%, and 50%, respectively, while the rates of live birth and neonatal survival were 98.7% and 98.2%, respectively. The rate of term birth was highest (70.6%) and the birth weight was heaviest (2931 ± 535 g) in Group 1 (p = 0.000). In the presence of a fetus subjected to feticide, the mean delivery age was earlier than that in the non-presenting group (p = 0.017); accordingly, the mean birth weight in the feticide group was lower (2366 ± 628 g) than that in the non-presenting group (2590 ± 634 g) (p = 0.011). When we examined the relative relationship between reduction weeks and delivery weeks of twins by correlation analysis, we observed that with regard to maternal prognosis, two pregnancies involved preterm premature rupture of membranes (PPROM) at 7 days and 3 days after the procedure. Intrauterine infection occurred in two patients in Group 4, but there were no maternal deaths or maternal coagulatory abnormalities. CONCLUSIONS: Optimal perinatal outcomes were obtained by ST of DCDA pregnancies before 18 weeks, regardless of whether or not the reduced fetus was the presenting twin. However, if legally possible, late (i.e., after 28 weeks) procedures can be a safe alternative for patients diagnosed after the 18th week of gestation. Overall, we herein noted a negative correlation between the procedure week and the delivery week in this study. Moreover, ST of the non-presenting twin was associated with a heavier birth weight and later gestational age at delivery.

20.
J Acoust Soc Am ; 155(2): 1240-1252, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341749

RESUMO

The orbital angular momentum (OAM) wave has shown great potential for improving radar imaging and underwater communication performance due to its helical wavefront phase and infinite orthogonal modes. However, there are currently no known applications of this technology in underwater imaging. In this paper, we employed acoustic OAM wave for underwater imaging and established transceiver signal models using the uniform circular array. We concurrently achieved two-dimensional imaging of azimuth and elevation angles, which differs from radar imaging. We proposed a matching process for the echo signal in the modal domain, the OAM wave beam image's sidelobe decreased by 7.9 dB in the elevation direction and 6.1 dB in the azimuth direction compared to the plane wave, with the mainlobe decreased by 0.2° in the elevation direction and 0.4° in the azimuth direction. Furthermore, this paper introduced OAM wave high-resolution image reconstruction based on the orthogonal matching pursuit (OMP) algorithm. Finally, we implemented broadband acoustic OAM wave for underwater imaging and introduced an image reconstruction method based on the modal domain OMP algorithm. Simulation results demonstrate that the use of OAM wave in underwater imaging is feasible, and the proposed scheme can achieve high-resolution imaging.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa