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This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57 to 1.29. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer's V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.
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Anus Imperfurado , Ultrassonografia Pré-Natal , Humanos , Feminino , Estudos Prospectivos , Ultrassonografia Pré-Natal/métodos , Gravidez , Anus Imperfurado/diagnóstico por imagem , Curva ROC , Adulto , Recém-Nascido , IncidênciaRESUMO
BACKGROUND: This research aims to summarize the ultrasound features and pregnancy outcomes of incarceration of the gravid uterus (IGU), providing a basis for clinical management. METHODS: A retrospective cohort study was conducted on pregnant patients with IGU at Hunan Provincial Maternal and Child Health Care Hospital in China, spanning from September 30, 2016, to May 31, 2024. Data on maternal age, parity, medical history, risk factors, gestational age, clinical manifestations, ultrasound examination, treatment methods, time, and method for terminating pregnancy, and pregnancy outcomes were collected. We compared cases diagnosed before and after 20 gestational weeks. RESULTS: During the study period, 13 pregnant women were diagnosed with IGU, and 140 162 deliveries were recorded at our hospital. Two cases were referred from other hospitals and did not deliver in our hospital. Accordingly, the incidence of IGU was 0.08 (11/140, 162). The most prevalent risk factor for IGU was previous abdominal or pelvic surgery (61.54%, 8/13). Dysuria or even urinary retention was the primary symptom (38.46%, 5/13). Spontaneous resolution occurred in only one case (7.69%). All cases were detected using prenatal ultrasound examination with typical characteristics, including a retroverted uterus and the fundus located behind the cervix. No statistically significant differences between the two comparison groups were found in successful uterine reduction (p > 0.05). CONCLUSION: The definition of IGU should include symptomatic cases of any gestational age. Despite a low prevalence of this pregnancy complication, the overall prognosis of IGU is good. In the absence of severe symptoms, regular monitoring may be an option. Typical ultrasound imaging features enable a definitive diagnosis of IGU.
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BACKGROUND AND AIMS: Although water channel aquaporin-8 (AQP8) has been implicated in hepatic bile formation and liver diseases associated with abnormal bile flow in human and animal studies, direct evidence of its involvement in bile secretion is still lacking. This study aimed to determine the role of AQP8 in bile secretion and gallstone formation. METHODS: We generated various transgenic knock-in and knockout mouse models and assessed liver AQP8 expression by immunostaining and immunoblotting, hepatic bile secretion by cannulation of the common bile duct, cholesterol gallstone formation by feeding a high-fat lithogenic diet, and identified regulatory small molecules by screening the organic fractions of cholagogic Chinese herbs and biochemical characterization. RESULTS: We identified a novel expression pattern of AQP8 protein in the canalicular membrane of approximately 50% of the liver lobules. AQP8-deficient mice exhibited impaired hepatic bile formation, characterized by the secretion of concentrated bile with a lower flow rate and higher levels of bile lipids than that of wild-type littermates. AQP8-/- mice showed accelerated gallstone formation, which was rescued by AAV-mediated hepatic expression of AQP8 or AQP1. Moreover, we identified a small molecule, scutellarin, that upregulates hepatocyte AQP8 expression in vitro and in vivo. In AQP8+/+ mice, scutellarin significantly increased bile flow, decreased bile lipid concentrations, and prevented gallstone formation compared to AQP8-/- mice. Molecular studies revealed that scutellarin promoted the ubiquitination and degradation of HIF-1α, a transcriptional negative regulator of AQP8, by disrupting its interactions with HSP90. CONCLUSIONS: AQP8 plays a crucial role in facilitating water transport and bile dilution during hepatic bile formation, thereby mitigating gallstone formation in mice. Small-molecule intervention validated hepatocyte AQP8 as a promising drug target for gallstone therapy. IMPACT AND IMPLICATIONS: The incidence of gallstone disease is high, and current drug treatments for gallstones are very limited, necessitating the identification of novel drug targets for developing new drugs with universal applicability. To our knowledge, this is the first study to provide direct evidence that hepatic water channel AQP8 plays a key role in bile dilution and gallstone formation. Modulation of hepatic water transport may provide a universal therapeutic strategy for all types of gallstone diseases.
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α-Silyl alcohols are powerful structural motifs for pharmaceutical chemistry, materials chemistry, and organic synthesis. The limitations of current synthetic techniques encompass a requirement for difficult-to-obtain silyl precursors, noble-metal catalysts, and narrow substrate scopes. Here, we developed a general synthetic method for α-silyl alcohols through electroreductive cross-coupling of aldehydes and chlorosilane. This method features easily available reagents, mild conditions, and a wide substrate scope. The establishment of this protocol will provide an alternative for access to α-silyl alcohols.
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BACKGROUND: Periventricular-intraventricular hemorrhage can lead to posthemorrhagic ventricular dilatation or even posthemorrhagic hydrocephalus if not detected promptly. Sequential cranial ultrasound scans are typically used for their diagnoses. Nonetheless, manual image audit has numerous disadvantages. PURPOSE: This study aimed to develop a predictive model utilizing modified inception (MI) and high-level feature-guided attention (HFA) modules for predicting neonatal lateral ventricular dilation via ultrasound images. METHODS: The MI modules reduced input data sizes and dimensions, while the HFA modules effectively delved into semantic information through supervision from high-level feature images to low-level feature images. The process facilitated the accurate identification of dilated lateral ventricles. A total of 710 neonates, corresponding to 1420 lateral ventricles, were recruited in this study. Each lateral ventricle was captured in two images, one on the parasagittal plane and the other on the coronal plane. The combination of anterior horn width, ventricular index, thalamo-occipital distance, and ventricular height served as the gold standard. A lateral ventricle would be considered dilatated if any of these four indices exceeded its upper reference value. These lateral ventricles were randomly split into training and testing sets at a 7:3 ratio. We evaluated the validity of our proposed approach and its competitors across the coronal plane, parasagittal plane, and overall performance. We also determined the impact of subjects' baseline characteristics on the overall performance of the proposed approach. Additionally, ablation analyses were conducted to ensure the efficacy of the proposed approach. RESULTS: Our proposed approach achieved the largest Youden index (0.65, 95% CI: 0.58-0.72), DOR (27.11, 95% CI: 15.89-46.26), area under curves (AUC) of receiver operating characteristic curve (ROC) (0.84, 95% CI: 0.80-0.88), and AUC of precision-recall curve (PRC) (0.81, 95% CI: 0.74-0.86) in the overall performance assessment and ablation analyses. Moreover, it boasted the biggest Cramer's V values on the coronal (Cramer's V = 0.488, p < 0.001) and parasagittal (Cramer's V = 0.713, p < 0.001) planes individually. Factors such as left side, male sex, singleton birth, and vaginal delivery were positively correlated with higher performance regarding the proposed algorithm, except for the gestational age. CONCLUSION: This work provides a novel attention optimized algorithm for rapid and accurate ventricular dilatation predictions. It surpasses the traditional algorithms in terms of validity whether concerning the coronal plane, parasagittal plane, or overall performance. The overall performance of algorithms will be influenced by the baseline characteristics of populations.
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The combined pollution of microplastics (MPs) and sulfamethoxazole (SMZ) often occurs in aquatic ecosystems, posing a serious threat to animal and human health. However, little is known about the liver damage caused by the single or co-exposure of MPs and SMZ, and its specific mechanisms are still poorly understood. In this study, we investigated the effects of co-exposure to 20 µm or 80â¯nm MPs and SMZ in both larval and adult zebrafish models. Firstly, we observed a significant decrease in the number of hepatocytes and the liver damage in larval zebrafish worsened following co-exposure to SMZ and MPs. Additionally, the number of macrophages and neutrophils decreased, while the expression of inflammatory cytokines and antioxidant enzyme activities increased after co-exposure in larval zebrafish. Transcriptome analysis revealed significant changes in gene expression in the co-exposed groups, particularly in processes related to oxidation-reduction, inflammatory response, and the MAPK signaling pathway in the liver of adult zebrafish. Co-exposure of SMZ and MPs also promoted hepatocyte apoptosis and inhibited proliferation levels, which was associated with the translocation of Nrf2 from the cytoplasm to the nucleus and an increase in protein levels of Nrf2 and NF-kB p65 in the adult zebrafish. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway partially rescued the liver injury induced by co-exposure both in larval and adult zebrafish. In conclusion, our findings suggest that co-exposure to SMZ and MPs induces hepatic dysfunction through the ROS-mediated MAPK signaling pathway in zebrafish. This information provides novel insights into the potential environmental risk of MPs and hazardous pollutants co-existence in aquatic ecosystems.
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Microplásticos , Espécies Reativas de Oxigênio , Sulfametoxazol , Poluentes Químicos da Água , Peixe-Zebra , Animais , Sulfametoxazol/toxicidade , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Larva/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Hepatócitos/efeitos dos fármacosRESUMO
Herein, electroreductive umpolung benzylic deuteration of p-QMs using cheap and easily accessible D2O as a deuterium source is reported. Various value-added benzylic deuterated diarylmethanes can be synthesized without the requirement of noble metal catalysts, redox reagents, and strong bases. The establishment of this protocol will provide an alternative strategy for acquiring benzylic deuterated diarylmethanes.
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Necroptotic immunogenic cell death (ICD) can activate the human immune system to treat the metastasis and recurrence of triple-negative breast cancer (TNBC). However, developing the necroptotic inducer and precisely delivering it to the tumor site is the key issue. Herein, we reported that the combination of shikonin (SHK) and chitosan silver nanoparticles (Chi-Ag NPs) effectively induced ICD by triggering necroptosis in 4T1 cells. Moreover, to address the lack of selectivity of drugs for in vivo application, we developed an MUC1 aptamer-targeted nanocomplex (MUC1@Chi-Ag@CPB@SHK, abbreviated as MUC1@ACS) for co-delivering SHK and Chi-Ag NPs. The accumulation of MUC1@ACS NPs at the tumor site showed a 6.02-fold increase compared to the free drug. Subsequently, upon reaching the tumor site, the acid-responsive release of SHK and Chi-Ag NPs from MUC1@ACS NPs cooperatively induced necroptosis in tumor cells by upregulating the expression of RIPK3, p-RIPK3, and tetrameric MLKL, thereby effectively triggering ICD. The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.
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Quitosana , Nanopartículas Metálicas , Naftoquinonas , Necroptose , Proteína Serina-Treonina Quinases de Interação com Receptores , Prata , Neoplasias de Mama Triplo Negativas , Naftoquinonas/farmacologia , Naftoquinonas/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Quitosana/química , Prata/química , Prata/farmacologia , Animais , Nanopartículas Metálicas/química , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Linhagem Celular Tumoral , Feminino , Necroptose/efeitos dos fármacos , Humanos , Camundongos , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Mucina-1/metabolismo , Sinergismo Farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/químicaRESUMO
2,3-Diaryl propanoic acids are important structures as a result of their widespread presence in numerous bioactive compounds. However, the limitations of existing synthetic techniques include the requirement for costly catalysts and limited substrates. Here, we developed a novel electroreductive arylcarboxylation of alkenes with CO2 based on a radical-polar crossover pathway assisted by easily accessible dimethyl terephthalate as a reductive mediator. This method will provide an efficient strategy for the synthesis of 2,3-diarylpropanoic acids.
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Both nanoplastics (NPs) and 3-tert-butyl-4-hydroxyanisole (3-BHA) are environmental contaminants that can bio-accumulate through the food chain. However, the combined effects of which on mammalian female reproductive system remain unclear. Here, the female ICR-CD1 mice were used to evaluate the damage effects of ovaries and uterus after NPs and 3-BHA co-treatment for 35 days. Firstly, co-exposure significantly reduced the body weight and organ index of ovaries and uterus in mice. Secondly, combined effects of NPs and 3-BHA exacerbated the histopathological abnormalities to the ovaries and uterus and decreased female sex hormones such as FSH and LH while increased antioxidant activities including CAT and GSH-Px. Moreover, the apoptotic genes, inflammatory cytokines and the key reproductive development genes such as FSTL1 were significantly up-regulated under co-exposure conditions. Thirdly, through transcriptional and bioinformatics analysis, immunofluorescence and western blotting assays, together with molecular docking simulation, we determined that co-exposure up-regulated the FSTL1, TGF-ß and p-Smad1/5/9 but down-regulated the expression of BMP4. Finally, the pharmacological rescue experiments further demonstrated that co-exposure of NPs and 3-BHA mainly exacerbated the female reproductive toxicity through FSTL1-mediated BMP4/TGF-ß/SMAD signaling pathway. Taken together, our studies provided the theoretical basis of new environmental pollutants on the reproductive health in female mammals.
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Camundongos Endogâmicos ICR , Ovário , Poliestirenos , Útero , Animais , Feminino , Camundongos , Útero/efeitos dos fármacos , Útero/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Poliestirenos/toxicidade , Reprodução/efeitos dos fármacos , Microplásticos/toxicidade , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Nanopartículas/toxicidade , Simulação de Acoplamento Molecular , Poluentes Ambientais/toxicidade , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genéticaRESUMO
Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid-parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over-parent heterosis or heterobeltiosis). Nonadditive expression and allele-specific gene expression assays showed that the glutathione S-transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt-sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72-OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice.
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Vigor Híbrido , Oryza , Vigor Híbrido/genética , Espécies Reativas de Oxigênio/metabolismo , Oryza/genética , Oryza/metabolismo , Tolerância ao Sal/genética , FenótipoRESUMO
This study aims at suggesting an end-to-end algorithm based on a U-net-optimized generative adversarial network to predict anterior neck lower jaw angles (ANLJA), which are employed to define fetal head posture (FHP) during nuchal translucency (NT) measurement. We prospectively collected 720 FHP images (half hyperextension and half normal posture) and regarded manual measurement as the gold standard. Seventy percent of the FHP images (half hyperextension and half normal posture) were used to fit models, and the rest to evaluate them in the hyperextension group, normal posture group (NPG), and total group. The root mean square error, explained variation, and mean absolute percentage error (MAPE) were utilized for the validity assessment; the two-sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, Bland-Altman plot, and intraclass correlation coefficient (ICC) for the reliability evaluation. Our suggested algorithm outperformed all the competitors in all groups and indices regarding validity, except for the MAPE, where the Inception-v3 surpassed ours in the NPG. The two-sample t test and Mann-Whitney U test indicated no significant difference between the suggested method and the gold standard in group-level comparison. The Wilcoxon signed-rank test revealed significant differences between our new approach and the gold standard in personal-level comparison. All points in Bland-Altman plots fell between the upper and lower limits of agreement. The inter-ICCs of ultrasonographers, our proposed algorithm, and its opponents were graded good reliability, good or moderate reliability, and moderate or poor reliability, respectively. Our proposed approach surpasses the competition and is as reliable as manual measurement.
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Mandíbula , Medição da Translucência Nucal , Humanos , Feminino , Gravidez , Reprodutibilidade dos Testes , Mandíbula/diagnóstico por imagem , Feto/diagnóstico por imagem , Cuidado Pré-NatalRESUMO
In the chemical investigation of Inula japonica, a total of 29 sesquiterpenoids (1-29) were obtained, including pseudoguaine-, xanthane-, eudesmane-, and 1,10-secoeudesmane-type compounds, as well as their dimers. Among them, six new dimeric sesquiterpenoids, bisinulains A-F (1-5, 7), characterized by a [4 + 2] biogenetic pathway between different sesquiterpenoid monomers were identified. Additionally, three new monomers named inulaterins A-C (13, 18 and 21) were discovered. The structures of these compounds were determined through analysis of spectroscopic data, X-ray crystallographic data, and ECD experiments. To assess their potential anti-inflammatory activities, the sesquiterpenoid dimers were tested for their ability to inhibit NO production in LPS-stimulated RAW 264.7 cells. Furthermore, the compounds that exhibited anti-inflammatory effects underwent evaluation for their anti-fibrotic potential using a TGF-ß-induced epithelial-mesenchymal transition model in A549 cells. As a result, bisinulain B (2) was screened out to significantly inhibit the production of cytokines involved in pulmonary fibrosis such as NO, α-SMA, collagen I and fibronectin.
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Inula , Sesquiterpenos , Animais , Camundongos , Humanos , Inula/química , Estrutura Molecular , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Células A549 , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Objective: To evaluate the changes in cardiac morphology of fetuses with congenital heart disease (CHD) using the fetal heart quantitative technique (fetalHQ).Methods: A total of 20 normal pregnant women (control group) and 20 pregnant women suspected of fetal CHD (case group) were included in this study. The dynamic images of the four-chamber view of the fetal heart were recorded and analyzed using fetalHQ. The global sphericity index (GSI) and 24-segment SI of the two groups were compared. The differences in the left and right ventricular 24-segment SI for each group were investigated.Results: There was no statistically significant difference in the GSI between the two groups (p > 0.05). The difference in the SI values of left ventricular segments 1-2 between the case group and control group was statistically significant (all p < 0.05), while the intergroup difference in SI of left ventricular segments 3-24 was not significant (all p > 0.05). The SI of the 24 segments of the right ventricle showed no significant intergroup difference (all p > 0.05). The difference in the left and right ventricular 24-segment SI in the case group did not reach statistical significance (all p > 0.05). In the control group, the SI values between the left and right ventricles were significantly different in segments 18-24 (all p < 0.05), and no significant difference was found in segments 1-17 (all p > 0.05). There was a statistically significant intergroup difference in the percentage of unusual left ventricular SI, determined based on Z-score (p < 0.05), and the percentage of outliers for the right ventricle between the two groups showed no significant difference (p > 0.05).Conclusion: The fetalHQ is regarded as a straightforward and reliable approach for assessing the cardiac GSI and 24-segment SI of left and right ventricles in fetuses diagnosed with CHD. While CHD may not significantly impact the overall shape of the fetal heart or the geometric shape of the right ventricle, in this study, a notable increase in SI values for the left ventricular 1-2 segments was observed, indicating a more flattened ventricular chamber. Additionally, the morphological distinctions between the left and right ventricles in fetuses with CHD are no longer discernible.
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Doenças Fetais , Cardiopatias Congênitas , Feminino , Humanos , Gravidez , Ultrassonografia Pré-Natal/métodos , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/anormalidadesRESUMO
BACKGROUND: The Glucan synthase-like (GSL) genes are indispensable for some important highly-specialized developmental and cellular processes involving callose synthesis and deposition in plants. At present, the best-characterized reproductive functions of GSL genes are those for pollen formation and ovary expansion, but their role in seed initiation remains unknown. RESULTS: We identified a rice seed mutant, watery seed 1-1 (ws1-1), which contained a mutation in the OsGSL2 gene. The mutant produced seeds lacking embryo and endosperm but filled with transparent and sucrose-rich liquid. In a ws1-1 spikelet, the ovule development was normal, but the microsporogenesis and male gametophyte development were compromised, resulting in the reduction of fertile pollen. After fertilization, while the seed coat normally developed, the embryo failed to differentiate normally. In addition, the divided endosperm-free nuclei did not migrate to the periphery of the embryo sac but aggregated so that their proliferation and cellularization were arrested. Moreover, the degeneration of nucellus cells was delayed in ws1-1. OsGSL2 is highly expressed in reproductive organs and developing seeds. Disrupting OsGSL2 reduced callose deposition on the outer walls of the microspores and impaired the formation of the annular callose sheath in developing caryopsis, leading to pollen defect and seed abortion. CONCLUSIONS: Our findings revealed that OsGSL2 is essential for rice fertility and is required for embryo differentiation and endosperm-free nucleus positioning, indicating a distinct role of OsGSL2, a callose synthase gene, in seed initiation, which provides new insight into the regulation of seed development in cereals.
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BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.
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COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , Adulto , SARS-CoV-2 , Gestantes , Complicações Infecciosas na Gravidez/diagnóstico , Feto , Placenta/diagnóstico por imagem , Líquido Amniótico , Transmissão Vertical de Doenças Infecciosas , Ultrassonografia Pré-NatalRESUMO
P23, historically known as a heat shock protein 90 (HSP90) co-chaperone, exerts some of its critical functions in an HSP90-independent manner, particularly when it translocates into the nucleus. The molecular nature underlying how this HSP90-independent p23 function is achieved remains as a biological mystery. Here, we found that p23 is a previously unidentified transcription factor of COX-2, and its nuclear localization predicts the poor clinical outcomes. Intratumor succinate promotes p23 succinylation at K7, K33, and K79, which drives its nuclear translocation for COX-2 transcription and consequently fascinates tumor growth. We then identified M16 as a potent p23 succinylation inhibitor from 1.6 million compounds through a combined virtual and biological screening. M16 inhibited p23 succinylation and nuclear translocation, attenuated COX-2 transcription in a p23-dependent manner, and markedly suppressed tumor growth. Therefore, our study defines p23 as a succinate-activated transcription factor in tumor progression and provides a rationale for inhibiting p23 succinylation as an anticancer chemotherapy.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Ácido Succínico , Fatores de Transcrição/genética , Ciclo-Oxigenase 2/genética , Piridinolcarbamato , Carcinogênese/genética , Transformação Celular Neoplásica , Succinatos , Adenocarcinoma de Pulmão/genética , Chaperonas Moleculares/genética , Proteínas de Choque Térmico HSP90/genética , Neoplasias Pulmonares/genéticaRESUMO
Crop reproductive development is vulnerable to heat stress, and the genetic modulation of thermotolerance during the reproductive phase, especially the early stage, remains poorly understood. We isolated a Poaceae-specific FAR-RED ELONGATED HYPOCOTYLS3 (FHY3)/FAR-RED IMPAIRED RESPONSE1 (FAR1)family transcription factor, Thermo-sensitive Spikelet Defects 1 (TSD1), derived from transposase in rice (Oryza sativa) TSD1 was highly expressed in spikelets, induced by heat, and specifically enhanced the thermotolerance of spikelet morphogenesis. Disrupting TSD1 did not affect vegetative growth but markedly retarded spikelet initiation and development, as well as caused varying degrees of spikelet degeneration, depending on the temperature. Most tsd1 spikelets were normal at low temperature but gradually degenerated as temperature increased, and all disappeared at high temperature, leading to naked branches. TSD1 directly promoted the transcription of YABBY1 and YABBY3 and could physically interact with YABBY1 and three TOB proteins, YABBY5, YABBY4, and YABBY3. These YABBY proteins can form either homodimers or heterodimers and play an important role in spikelet morphogenesis, similar to TSD1. Notably, the knockout mutant yab5-ko and double mutant tsd1 yab5-ko resembled tsd1 in spikelet appearance and response to temperature, indicating that these genes likely participate in spikelet development through the cooperative TSD1-YABBY module. These findings reveal a distinctive function of FHY3/FAR1 family genes and a unique TSD1-YABBY complex to acclimate spikelet development to high temperature in rice, providing insight into the regulating pathway of enhancing thermotolerance in plant reproductive development.