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1.
Cell ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39181133

RESUMEN

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.

2.
Nature ; 618(7967): 1041-1048, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37165191

RESUMEN

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.


Asunto(s)
Cromosomas Humanos , Cromotripsis , Micronúcleos con Defecto Cromosómico , Mitosis , Humanos , Centrómero , Cromosomas Humanos/genética , ADN/genética , ADN/metabolismo , Variaciones en el Número de Copia de ADN , Interfase , Mitosis/genética , Neoplasias/genética
3.
Plant Physiol ; 195(4): 3053-3071, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38717740

RESUMEN

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.


Asunto(s)
Ácido Abscísico , Sequías , Regulación de la Expresión Génica de las Plantas , Glycine max , Proteínas de Plantas , Estrés Fisiológico , Factores de Transcripción , Glycine max/genética , Glycine max/fisiología , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Fisiológico/genética , Transducción de Señal/genética
4.
Chem Soc Rev ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269194

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-33824062

RESUMEN

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.


Asunto(s)
Cromotripsis , Neoplasias , Aberraciones Cromosómicas , Reordenamiento Génico/genética , Genoma , Humanos , Neoplasias/genética
6.
J Gen Virol ; 105(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38602389

RESUMEN

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.


Asunto(s)
Hemípteros , Orthobunyavirus , Virus ARN , Animales , Femenino , Filogenia , Insectos , Virus ARN/genética
7.
Small ; 20(25): e2310180, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38342676

RESUMEN

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.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Temperatura , Humanos , Estroncio/química , Iterbio/química , Luminiscencia , Neodimio/química , Mediciones Luminiscentes/métodos , Rayos Infrarrojos
8.
Planta ; 259(4): 76, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418674

RESUMEN

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.


Asunto(s)
Arabidopsis , Glycine max , Humanos , Glycine max/genética , Arabidopsis/genética , Estrés Fisiológico/genética , Estrés Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética
9.
Histochem Cell Biol ; 161(2): 195-205, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37874337

RESUMEN

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.


Asunto(s)
Prolapso de Órgano Pélvico , Calidad de Vida , Femenino , Humanos , Transducción de Señal , Prolapso de Órgano Pélvico/metabolismo , Prolapso de Órgano Pélvico/patología , Vagina/metabolismo , Vagina/patología , Luciferasas/metabolismo
10.
Toxicol Appl Pharmacol ; 487: 116960, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735592

RESUMEN

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.


Asunto(s)
Apoptosis , Neoplasias Colorrectales , Sistema de Señalización de MAP Quinasas , Xilulosa , Humanos , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Xilulosa/farmacología , Xilulosa/metabolismo , Masculino , Animales , Femenino , Proliferación Celular/efectos de los fármacos , Heces/química , Persona de Mediana Edad , Línea Celular Tumoral , Antineoplásicos/farmacología , Células HT29 , Anciano
11.
J Theor Biol ; 577: 111673, 2024 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-37984586

RESUMEN

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.


Asunto(s)
Transición Epitelial-Mesenquimal , Redes Reguladoras de Genes , Diferenciación Celular , Retroalimentación
12.
J Org Chem ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294860

RESUMEN

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 ; 45(9): 1964-1977, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38698214

RESUMEN

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.


Asunto(s)
Antineoplásicos , Proliferación Celular , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Neoplasias de la Próstata , Quinolinas , Masculino , Animales , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Quinolinas/farmacología , Quinolinas/química , Quinolinas/uso terapéutico , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Agonismo Inverso de Drogas , Ratones , Ratones Desnudos , Descubrimiento de Drogas , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C
14.
BMC Pregnancy Childbirth ; 24(1): 391, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807069

RESUMEN

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.


Asunto(s)
Corion , Resultado del Embarazo , Embarazo Triple , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Recién Nacido , Adulto , Resultado del Embarazo/epidemiología , Peso al Nacer , Trillizos , Muerte Fetal/etiología
15.
Lipids Health Dis ; 23(1): 6, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38185620

RESUMEN

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.


Asunto(s)
Interleucina-17 , Psoriasis , Humanos , Animales , Ratones , Interleucina-17/genética , Cromatografía de Gases y Espectrometría de Masas , Lipidómica , Psoriasis/tratamiento farmacológico , Ácidos Grasos , Ácidos Grasos Monoinsaturados , Imiquimod , Anticuerpos Monoclonales/uso terapéutico
16.
BMC Public Health ; 24(1): 365, 2024 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310254

RESUMEN

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.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Tenofovir/uso terapéutico , Depresión/epidemiología , Fármacos Anti-VIH/uso terapéutico , Cumplimiento de la Medicación , Conducta Sexual , Ansiedad/epidemiología , China/epidemiología
17.
Arch Gynecol Obstet ; 310(2): 1027-1035, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38431699

RESUMEN

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.


Asunto(s)
Cesárea , Diabetes Gestacional , Síndromes de Preexcitación , Resultado del Embarazo , Taquicardia Supraventricular , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Resultado del Embarazo/epidemiología , Síndromes de Preexcitación/epidemiología , Síndromes de Preexcitación/complicaciones , China/epidemiología , Taquicardia Supraventricular/epidemiología , Taquicardia Supraventricular/etiología , Cesárea/estadística & datos numéricos , Diabetes Gestacional/epidemiología , Complicaciones Cardiovasculares del Embarazo/epidemiología , Adulto Joven
18.
J Acoust Soc Am ; 155(2): 1240-1252, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38341749

RESUMEN

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.

19.
J Integr Plant Biol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041924

RESUMEN

Light is one of the most essential environmental factors that tightly and precisely control various physiological and developmental processes in plants. B-box CONTAINING PROTEINs (BBXs) play central roles in the regulation of light-dependent development. In this study, we report that BBX9 is a positive regulator of light signaling. BBX9 interacts with the red light photoreceptor PHYTOCHROME B (phyB) and transcription factors PHYTOCHROME-INTERACTING FACTORs (PIFs). phyB promotes the stabilization of BBX9 in light, while BBX9 inhibits the transcriptional activation activity of PIFs. In turn, PIFs directly bind to the promoter of BBX9 to repress its transcription. On the other hand, BBX9 associates with the positive regulator of light signaling, BBX21, and enhances its biochemical activity. BBX21 associates with the promoter regions of BBX9 and transcriptionally up-regulates its expression. Collectively, this study unveiled that BBX9 forms a negative feedback loop with PIFs and a positive one with BBX21 to ensure that plants adapt to fluctuating light conditions.

20.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2710-2721, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812171

RESUMEN

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.


Asunto(s)
Carbón Orgánico , Medicamentos Herbarios Chinos , Hemostáticos , Ratas Sprague-Dawley , Sanguisorba , Animales , Ratas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Hemostáticos/farmacología , Hemostáticos/química , Sanguisorba/química , Carbón Orgánico/química , Masculino , Culinaria , Coagulación Sanguínea/efectos de los fármacos , Humanos
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