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Gestational diabetes mellitus (GDM) is a common complication of pregnancy, which has significant adverse effects on both the mother and fetus. The incidence of GDM is increasing globally, and early diagnosis is critical for timely treatment and reducing the risk of poor pregnancy outcomes. GDM is usually diagnosed and detected after 24 weeks of gestation, while complications due to GDM can occur much earlier. Copy number variations (CNVs) can be a possible biomarker for GDM diagnosis and screening in the early gestation stage. In this study, we proposed a machine-learning method to screen GDM in the early stage of gestation using cell-free DNA (cfDNA) sequencing data from maternal plasma. Five thousand and eighty-five patients from north regions of Mainland China, including 1942 GDM, were recruited. A non-overlapping sliding window method was applied for CNV coverage screening on low-coverage (~0.2×) sequencing data. The CNV coverage was fed to a convolutional neural network with attention architecture for the binary classification. The model achieved a classification accuracy of 88.14%, precision of 84.07%, recall of 93.04%, F1-score of 88.33% and AUC of 96.49%. The model identified 2190 genes associated with GDM, including DEFA1, DEFA3 and DEFB1. The enriched gene ontology (GO) terms and KEGG pathways showed that many identified genes are associated with diabetes-related pathways. Our study demonstrates the feasibility of using cfDNA sequencing data and machine-learning methods for early diagnosis of GDM, which may aid in early intervention and prevention of adverse pregnancy outcomes.
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Ácidos Nucleicos Livres , Aprendizado Profundo , Diabetes Gestacional , beta-Defensinas , Feminino , Gravidez , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Variações do Número de Cópias de DNA , Resultado da Gravidez , Ácidos Nucleicos Livres/genéticaRESUMO
This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 µm), PM1-2.5 (1-2.5 µm), and PM1 (≤1 µm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 µg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 µg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.
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Autoimunidade , Material Particulado , Glândula Tireoide , Humanos , Feminino , Gravidez , Adulto , China , Estudos Prospectivos , Poluentes Atmosféricos , Exposição MaternaRESUMO
Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.
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Creatinina , Resultado da Gravidez , Ácido Úrico , Humanos , Gravidez , Feminino , Estudos Prospectivos , Adulto , Creatinina/sangue , Ácido Úrico/sangue , Resultado da Gravidez/epidemiologia , Recém-Nascido , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Primeiro Trimestre da Gravidez/sangue , Cesárea/estatística & dados numéricos , Fatores de Risco , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Idade Materna , China/epidemiologiaRESUMO
BACKGROUND: Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS-STING in SAP-induced lung injury (LI) remains unknown. METHODS: Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS -/- and sting -/- mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro. RESULTS: SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA-cGAS-STING axis and the NLRP3-pyroptosis axis. CONCLUSIONS: Negative regulation of any molecule in the mtDNA-cGAS-STING-IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.
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DNA Mitocondrial , Fator Regulador 3 de Interferon , Lesão Pulmonar , Macrófagos , Proteínas de Membrana , Nucleotidiltransferases , Pancreatite , Piroptose , Transdução de Sinais , Animais , Piroptose/genética , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 3 de Interferon/genética , Camundongos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Pancreatite/metabolismo , Pancreatite/genética , Pancreatite/patologia , Pancreatite/induzido quimicamente , Macrófagos/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Fator Regulador 7 de Interferon/metabolismo , Fator Regulador 7 de Interferon/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Inflamassomos/metabolismo , Lipopolissacarídeos , Masculino , Modelos Animais de DoençasRESUMO
BACKGROUND: Remnant cholesterol (RC) reportedly contributes to the development of diabetes mellitus. However, evidence on the relationship between maternal RC and the risk of developing gestational diabetes mellitus (GDM) during pregnancy is limited. This study aimed to assess the relationship between maternal RC and GDM risk during early pregnancy, and explore the potential pathways involved in the relationship between RC levels and GDM risk. METHODS: From 2018 to 2021, a prospective birth cohort study was designed and carried out in China. The associations of maternal RC and other lipid parameters with GDM risk were estimated using logistic regression models and restricted cubic splines. Subgroup analyses were performed stratified by prepregnancy body mass index (pre-BMI), maternal age and gravidity. Mediation analyses were conducted to explore the mediating effect of some related factors on the relationship between RC levels and the risk of GDM. RESULTS: A total of 33,018 pregnant women were included. The median RC level was 0.47 ± 0.20 mmol/L. The prevalence of GDM was 15.19%. As RC quartiles increased, the incidence of GDM increased substantially, reaching 19.24% for the highest quartile of RC (P < 0.001). Maternal RC in the first trimester was positively correlated with GDM risk (OR: 2.254, 95% CI: 1.943-2.615). Compared to the lowest RC quartile, higher RC quartiles were correlated with an increased risk of GDM, and the ORs (95% CIs) for Q3 and Q4 were 1.208 (1.101-1.325) and 1.489 (1.364-1.626), respectively. Moreover, a linear dose-response relationship was found for this association (P for all < 0.001, P for nonlinearity > 0.05) and was consistent across subgroups with different pre-BMIs, maternal ages and gravidities (all P values for interactions > 0.05). Furthermore, the correlation between RC level and GDM risk was partially mediated by pre-BMI (9.20%) and blood glucose level (-11.1%). CONCLUSIONS: Higher maternal RC levels in the early stage of pregnancy was positively associated with an increased risk of developing GDM. This association was partially mediated by pre- BMI and blood glucose levels.
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Índice de Massa Corporal , Colesterol , Diabetes Gestacional , Humanos , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Gravidez , Feminino , Adulto , Estudos Prospectivos , Colesterol/sangue , Fatores de Risco , China/epidemiologia , Primeiro Trimestre da Gravidez/sangue , Modelos LogísticosRESUMO
BACKGROUND: Subclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear. METHODS: We enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves. RESULTS: In the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C < 1.06 mmol/L, and TC > 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve. CONCLUSIONS: Among pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes.
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Diabetes Gestacional , Dislipidemias , Eclampsia , Hipertensão Induzida pela Gravidez , Hipotireoidismo , Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Estudos de Coortes , Gestantes , LDL-Colesterol , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Diabetes Gestacional/epidemiologia , Tireotropina , Triglicerídeos , Lipoproteínas HDLRESUMO
The electrocardiogram (ECG) signal is susceptible to interference from unknown noises during the acquisition process due to their low frequency and amplitude, resulting in the loss of significant information in the signals. Recent advancements in deep learning models have shown promising results in signal processing. However, these models lack robustness against various types of noise and often overlook the gradient difference between denoised and original signals. In this study, we propose a novel deep learning denoising method based on an attention half instance normalization block (AHIN block) and a gradient difference max loss function (GDM Loss). Our approach consists of two stages: firstly, we input the noisy ECG signal to obtain a denoised version; secondly, we reconstruct the denoised signal by fusing preliminary results from the first stage while correcting waveform distortions caused by initial denoising to minimize information loss. Additionally, we introduce a new loss function that considers differences between slopes of the denoised ECG signal and clean ECG signal. To validate our proposed method's effectiveness, extensive experiments were conducted on both our model architecture and loss function compared with other state-of-the-art methods. Results demonstrate that our approach achieves excellent performance in terms of both signal-to-noise ratio (SNR) and root-mean-square error (RMSE). The proposed noise reduction method improves 8.86%, 12.05% and 10.50% respectively under BW, MA and EM noise.
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One vision-threatening side effect of systematic diabetes mellitus is diabetic retinopathy (DR). Recent studies have revealed that the development and progression of DR depend critically on inflammation resulting from diabetes. By attracting leukocytes to endothelium, the higher production of the inflammatory mediators induces degeneration of retinal capillaries, hence increasing vascular permeability and thrombosis probability. The leukocytes that are recruited eventually generate additional proinflammatory and proangiogenic substances, resulting in the increased infiltration of leukocytes in the retina. This process also leads to changes in the blood retinal barrier and the formation of new blood vessels, which helps to counteract the damage caused by the blockage of blood flow. IL-12 family members, IL-12, IL-23, IL-27, and IL-35, play a crucial role in regulating the responses of T helper (Th)1 and Th17 cell populations. The collected data from studies investigating the levels of IL-12 family members in the blood and eye tissues suggest that IL-12 is linked to DR, indicating that it may have a role in the development of DR as a sequential component of the immune response. This review specifically examines the possibility of using IL-12 family cytokines as a therapeutic approach for diabetes, taking into consideration their involvement in the development of DR.
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Synthetic biology-based engineering of Saccharomyces cerevisiae to produce terpenoid natural products is an effective strategy for their industrial application. Previously, we observed that glycerol addition was beneficial for ginsenoside compound K (CK) production in a S. cerevisiae when it was fermented using the YPD medium. Here, we reconstructed the CK synthesis and glycerol catabolic pathway in a high-yield protopanaxadiol (PPD) S. cerevisiae strain. Remarkably, our engineered strain exhibited the ability to utilize glycerol as the sole carbon source, resulting in a significantly enhanced production of 433.1 ± 8.3 mg L-1 of CK, which was 2.4 times higher compared to that obtained in glucose medium. Transcriptomic analysis revealed that the transcript levels of several key genes involved in the mevalonate (MVA) pathway and the uridine diphosphate glucose (UDPG) synthesis pathway were up-regulated in response to glycerol. The addition of glycerol enhanced CK titers by augmenting the flux of the terpene synthesis pathway and facilitating the production of glycosyl donors. These results suggest that glycerol is a promising carbon source in S. cerevisiae, especially for the production of triterpenoid saponins.
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Ginsenosídeos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Glicerol/metabolismo , Transcriptoma/genética , Engenharia Metabólica , Fermentação , Proteínas de Saccharomyces cerevisiae/metabolismo , Carbono/metabolismoRESUMO
Objective: Unilateral mastectomy is known to induce postural alterations, yet the temporal development pattern of these changes remains elusive. This study aimed to explore the impact of unilateral mastectomy on body posture. Methods: A prospective, longitudinal, observational study with a one-group repeated-measures design was conducted. Patients undergoing unilateral mastectomy were recruited from a university-affiliated hospital in Western China and monitored for 12 months post-surgery. A trained nurse assessed seven postural baseline parameters on the day of suture removal and at 3, 6, and 12 months after unilateral mastectomy. Two parameters were in the sagittal plane (forward head posture and trunk rotation angle), and five were in the coronal plane (neck tilt, shoulder asymmetry, scapular asymmetry, scapular asymmetry relative to the spine, and pelvic tilt). Results: The final analysis included 159 patients. Baseline prevalence of most postural abnormalities ranged from 50.94% to 59.75%, with mean deviations between 2.74 and 4.51 mm. At 12 months post-mastectomy, prevalence and mean deviations increased by more than 30% and 3.50 mm, respectively, compared to baseline. Postural abnormalities increased gradually in the first 3 months, notably between the 3rd and 6th months, and slowed between the 6th and 12th months. On the mastectomy side, coronal plane abnormalities significantly increased within 12 months: earlobe to acromion distance (Wald χ2 = 45.283, P < 0.001), depressed shoulder height (Wald χ2 = 42.253, P < 0.001), depressed scapula height (Wald χ2 = 31.587, P < 0.001), scapula to spine distance (Wald χ2 = 45.283, P < 0.001), and elevated pelvic height (Wald χ2 = 48.924, P < 0.001). Conclusions: Postural changes are common post-unilateral mastectomy, with prevalence and deviation increasing gradually, particularly between 3 and 6 months post-mastectomy. Early rehabilitation initiation is recommended to mitigate postural changes. Trial registration: ChiCTR2000040897.
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This paper addresses the adaptive fixed-time fuzzy containment control for uncertain nonlinear multiagent systems, where the states and nonlinear functions are not feasible for the controller design. To address the issue of unmeasurable states, a state observer is developed, and fuzzy logic systems are utilized to approximate unknown nonlinear functions. Under the framework of fixed-time Lyapunov function theory and cooperative control, an adaptive fixed-time fuzzy containment control protocol is derived via the adaptive backstepping and adding one power integrator method. The derived fixed-time containment controller can confirm that the closed-loop systems are practical fixed-time stable, which implies that all signals in the systems are bounded and all follower agents can converge to the convex hull formed by the leader agents within fixed-time in the presence of unmeasurable states and unknown nonlinear functions . Simulation examples are conducted to test the validity of the present control algorithm.
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Selective conversion of inert C-H bonds in alkanes into high-value-added functional groups (alcohols, ketones, carboxylic acids, etc.) plays a vital role in establishing a green and sustainable chemical industry. Catalytic selective oxidation of cyclohexane to KA oil (cyclohexanol and cyclohexanone) is a typical representative of alkane functionalization. In this work, hollow cage-like Co3O4 (Co3O4-C) and particle Co3O4 (Co3O4-P) were synthesized by calcining two types of Prussian blue analogues (PBAs), which were used to catalyze the selective oxidation of cyclohexane. The Co3O4-C predominantly exposed (311) crystal plane is easier to adsorb cyclohexane than Co3O4-P, which is beneficial to shorten the induction period, accelerate the reaction rate, and improve the conversion. Consequently, Co3O4-C displayed a 10% conversion of cyclohexane within 1 h, and the KA oil selectivity reached 90%. The Co3O4-P exposed (220) crystal plane has a higher molar percentage of oxygen vacancies and more active oxygen species, as well as a strong cyclohexanone adsorption capacity, which is conducive to the deep oxidation of cyclohexanone to adipic acid and other diacid products. The mechanism analysis of cyclohexane oxidation catalyzed by PBA-based Co3O4 shows that it exemplifies the feasibility to tailor the surface of catalysts by modulating the PBAs, which ultimately influences their reaction performance for accelerating the reaction and maintaining high cyclohexane conversion and KA oil selectivity.
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The adoption of photothermal synergistic catalysis for cyclohexane oxidation can balance the advantages of high conversion of thermal catalysis and high selectivity of photocatalytic technology to achieve better catalytic performance. Here, we prepared functional carbon nitride (BCA-CN) by self-assembly strategy of ionic liquid [Bmim]CA (1-Butyl-3-methylimidazole citrate) with melamine and cyanuric acid utilizing abundant elements and anionic/cationic hydrogen bonding interactions. The introduction of [Bmim]CA embeds C-C (carbon and carbon band) and C-O-C (ether bond) structures into graphitic carbon nitride (g-C3N4) framework, significantly improving light absorption capacity and migration of photo generated charge carriers. Compared to g-C3N4, both BCA-CN increases cyclohexane conversion and KA oil (the mixture of cyclohexanol and cyclohexanone) selectivity by 1.3 times under photothermal catalysis. The surface reactions are facilitated by changing adsorption sites of cyclohexane to increase adsorption energy and obtaining more hydroxyl radicals and superoxide radicals. Furthermore, the enhanced selectivity is attributed to the difficulty in generating cyclohexanone radicals. This work offers the reference scheme for the development of efficient photothermal catalysts in the selective oxidation of cyclohexane.
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The pathogenesis of neuropathic pain (NP) is complex, and there are various pathological processes. Previous studies have suggested that lncRNA PCAT19 is abnormally expressed in NP conduction and affects the occurrence and development of pain. The aim of this study is to analyze the role and mechanism of PCAT19 in NP induced by chronic compressive nerve injury (CCI) in mice. In this study, C57BL/6 mice were applied to establish the CCI model. sh-PCAT19 was intrathecally injected once a day for 5 consecutive days from the second day after surgery. We discovered that PCat19 level was gradually up-regulated with the passage of modeling time. Downregulation of Iba-1-positive expression, M1/M2 ratio of microglia, and pro-inflammatory factors in the spinal cords of CCI-mice after PCat19 knock-downed was observed. Mechanically, the expression of miR-378a-3p was negatively correlated with KDM3A and PCat19. Deletion of KDM3A prevented H3K9me2 demethylation of BDNF promoter and suppressed BDNF expression. Further, KDM3A promotes CCI-induced neuroinflammation and microglia activation by mediating Brain-derived neurotrophic factor (BDNF) demethylation. Together, the results suggest that PCat19 may be involved in the development of NP and that PCat19 shRNA injection can attenuate microglia-induced neuroinflammation by blocking KDM3A-mediated demethylation of BDNF and BDNF release.
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Fator Neurotrófico Derivado do Encéfalo , MicroRNAs , Microglia , Neuralgia , RNA Longo não Codificante , Animais , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Dor Crônica/genética , Dor Crônica/metabolismo , Desmetilação , Modelos Animais de Doenças , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neuralgia/genética , Neuralgia/metabolismo , RNA Endógeno Competitivo , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: Premature ovarian insufficiency (POI) is a severe disorder leading to female infertility. Genetic mutations are important factors causing POI. TP63-truncating mutation has been reported to cause POI by increasing germ cell apoptosis, however what factors mediate this apoptosis remains unclear. METHODS: Ninety-three patients with POI were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Whole-exome sequencing (WES) was performed for each patient. Sanger sequencing was used to confirm potential causative genetic variants. A minigene assay was performed to determine splicing effects of TP63 variants. A TP63-truncating plasmid was constructed. Real-time quantitative PCR, western blot analyses, dual luciferase reporter assays, immunofluorescence staining, and cell apoptosis assays were used to study the underlying mechanism of a TP63-truncating mutation causing POI. RESULTS: By WES of 93 sporadic patients with POI, we found a 14-bp deletion covering the splice site in the TP63 gene. A minigene assay demonstrated that the 14-bp deletion variant led to exon 13 skipping during TP63 mRNA splicing, resulting in the generation of a truncated TP63 protein (TP63-mut). Overexpression of TP63-mut accelerated cell apoptosis. Mechanistically, the TP63-mut protein could bind to the promoter region of CLCA2 and activate the transcription of CLCA2 several times compared to that of the TP63 wild-type protein. Silencing CLCA2 using a specific small interfering RNA (siRNA) or inhibiting the Ataxia Telangiectasia Mutated (ATM) pathway using the KU55933 inhibitor attenuated cell apoptosis caused by TP63-mut protein expression. CONCLUSION: Our findings revealed a crucial role for CLCA2 in mediating apoptosis in POI pathogenesis, and suggested that CLCA2 is a potential therapeutic target for POI.
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Menopausa Precoce , Insuficiência Ovariana Primária , Fatores de Transcrição , Proteínas Supressoras de Tumor , Feminino , Humanos , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Éxons , Menopausa Precoce/genética , Mutação , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteínas Supressoras de Tumor/genéticaRESUMO
Submerged plants affect nitrogen cycling in aquatic ecosystems. However, whether and how submerged plants change nitrous oxide (N2O) production mechanism and emissions flux remains controversial. Current research primarily focuses on the feedback from N2O release to variation of substrate level and microbial communities. It is deficient in connecting the relative contribution of individual N2O production processes (i.e., the N2O partition). Here, we attempted to offer a comprehensive understanding of the N2O mitigation mechanism in aquatic ecosystems on the Changjiang River Delta according to stable isotopic techniques, metagenome-assembly genome analysis, and statistical analysis. We found that the submerged plant reduced 45 % of N2O emissions by slowing down the dissolved inorganic nitrogen conversion velocity to N2O in sediment (Vf-[DIN]sed). It was attributed to changing the N2O partition and suppressing the potential capacity of net N2O production (i.e., nor/nosZ). The dominated production processes showed a shift with increasing excess N2O. Meanwhile, distinct shift thresholds of planted and unplanted habitats reflected different mechanisms of stimulated N2O production. The hotspot zone of N2O production corresponded to high nor/nosZ and unsaturated oxygen (O2) in unplanted habitat. In contrast, planted habitat hotspot has lower nor/nosZ and supersaturated O2. O2 from photosynthesis critically impacted the activities of N2O producers and consumers. In summary, the presence of submerged plants is beneficial to mitigate N2O emissions from aquatic ecosystems.
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Ecossistema , Óxido Nitroso , Rios , China , Rios/química , Óxido Nitroso/análise , Plantas , Monitoramento Ambiental , Poluentes Atmosféricos/análiseRESUMO
BACKGROUND: Polycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PURPOSE: This study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. STUDY DESIGN AND METHODS: Polycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. RESULTS: Baicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. CONCLUSIONS: Our findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.
Assuntos
Ferroptose , Flavanonas , Ovário , Estresse Oxidativo , Placenta , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Flavanonas/farmacologia , Ferroptose/efeitos dos fármacos , Animais , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Placenta/efeitos dos fármacos , Placenta/metabolismo , Ovário/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis/química , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , MasculinoRESUMO
The high photoelectric conversion efficiency and low cost of perovskite solar cells (PSCs) have further inspired people's determination to push this technology toward industrialization. The high-quality perovskite films and high-efficiency and stable PSCs are the crucial factors. Ionic liquids have been proven to be an effective strategy for regulating high-quality perovskite films and high-performance PSCs. However, the regulation mechanism between ionic liquids and perovskites still needs further clarification. In this study, a novel sulfonic acid-functionalized ionic liquid, 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BSO3HMImOTf), was used as an effective additive to regulate high-quality perovskite films and high-performance devices. Microscopic mechanism studies revealed strong interactions between BSO3HMImOTf and Pb2+ ions as well as halogens in the perovskite. The perovskite film is effectively passivated with the controlled crystal growth, suppressed ion migration, facilitating to the greatly improved photovoltaic performance, and superior long-term stability. This article reveals the regulatory mechanism of sulfonic acid type ionic liquids through testing characterization and mechanism analysis, providing a new approach for the preparation of high-quality perovskite devices.
RESUMO
Photocured room temperature phosphorescent (RTP) materials hold great potential for practical applications but are scarcely reported. Here, we develop photocured RTP materials (P-Lig) using a combination of lignosulfonate, acrylamide, and ionic liquid (1-ethyl-3-methylimidazolium bromide). With this design, lignosulfonate simultaneously serves as RTP chromophore and photoinitiator. Specifically, lignosulfonate in the ionic liquid generates radicals to polymerize the acrylamide upon UV irradiation. The resulting lignosulfonate is automatically confined in an as-formed crosslinked matrix to provide RTP. As such RTP with an emission lifetime of ~110 ms is observed from the confined lignosulfonate in P-Lig. Additionally, energy transfer occur between P-Lig and Rhodamine B (RhB), triggering red afterglow emission when P-Lig is in situ loaded with RhB (P-Lig/RhB). As a demonstration of potential applications, the P-Lig and P-Lig/RhB are used as photocured RTP coatings and RTP inks for fabricating 3D materials and for information encryption.
RESUMO
Objective: To clarify the association between levothyroxine (LT4) treatment and various adverse pregnancy outcomes in pregnant women with thyrotropin (TSH) levels ranging between 2.5 and 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level. Methods: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5-10 mIU/L and normal free thyroxine levels (11.8-18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT4-treated and - untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5-4.0 mIU/L as high-normal group and 4.0-10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394). Results: Among the 4,370 pregnant women in the study, 1,342 received LT4 treatment and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT4 treatment was significantly associated with a decreased risk of pregnancy loss (RR = 0.528, 95% CI: 0.344-0.812) and an increased risk of small-for-gestational-age infants (RR = 1.595, 95% CI: 1.023-2.485). Subgroup analyses suggested that the above effects of LT4 treatment were mainly from TPOAb-negative participants. LT4 treatment was associated with an increased risk of preterm birth (RR = 2.214, 95% CI: 1.016-4.825) in TPOAb-positive pregnant women with high-normal TSH levels. Conclusion: LT4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5-10 mIU/L. An increased risk of preterm birth was observed in the LT4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.