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BACKGROUND: Elevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive. OBJECTIVE: We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes. METHODS: A large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 µmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB). RESULTS: sTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24-1.59]), SGA (aOR=1.31; [95 % CI: 1.18-1.46]), and PTB (aOR=1.27; [95 % CI: 1.15-1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %-63 %] for LBW, 24 % [95 % CI: 13 %-35 %] for SGA, and 34 % [95 % CI: 19 %-49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %-29 %], 4 % [-6%-14 %], 32 % [15 %-50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis. CONCLUSIONS: The substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level.
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Ácidos y Sales Biliares , Hipertensión Inducida en el Embarazo , Resultado del Embarazo , Humanos , Embarazo , Femenino , Ácidos y Sales Biliares/sangre , Adulto , China/epidemiología , Estudios Retrospectivos , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/epidemiología , Estudios de Cohortes , Recién Nacido , Nacimiento Prematuro/sangreRESUMEN
The bile acid sodium symporter (BASS) family plays an important role in transporting substances and coordinating plants' salt tolerance. However, the function of BASS in Brassica rapa has not yet been elucidated. In this study, eight BrBASS genes distributed on five chromosomes were identified that belonged to four subfamilies. Expression profile analysis showed that BrBASS7 was highly expressed in roots, whereas BrBASS4 was highly expressed in flowers. The promoter element analysis also identified several typical homeopathic elements involved in abiotic stress tolerance and stress-related hormonal responses. Notably, under salt stress, the expression of BrBASS2 was significantly upregulated; under osmotic stress, that of BrBASS4 increased and then decreased; and under cold stress, that of BrBASS7 generally declined. The protein-protein interaction analysis revealed that the BrBASS2 homologous gene AtBASS2 interacted with Nhd1 (N-mediated heading date-1) to alleviate salt stress in plants, while the BrBASS4 homologous gene AtBASS3 interacted with BLOS1 (biogenesis of lysosome-related organelles complex 1 subunit 1) via co-regulation with SNX1 (sorting nexin 1) to mitigate an unfavorable growing environment for roots. Further, Bra-miR396 (Bra-microRNA396) targeting BrBASS4 and BrBASS7 played a role in the plant response to osmotic and cold stress conditions, respectively. This research demonstrates that BrBASS2, BrBASS4, and BrBASS7 harbor great potential for regulating abiotic stresses. The findings will help advance the study of the functions of the BrBASS gene family.
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BACKGROUND: To use the three-dimensional (3D) ultrasound for assessment of pelvic floor muscle function in non-diabetic females with insulin resistance (IR), and to evaluate its functional relationship with insulin levels. METHODS: From October 2022 to November 2023, 216 non-diabetic females with insulin-resistant (IR group) and 118 normal females (control group) were sequentially recruited from our hospital for our study. The 3D ultrasound was used to assess the levator hiatus in resting state for all females regarding diameter lines, perimeters and areas; as well as the Valsalva manoeuvre (VM). The t-test and linear regression model were used to analyse the collected data. RESULTS: The analysis indicates that there were significant differences in the resting state of the levator hiatus between the IR and the control groups (14.8 ± 5.8 cm2 and 11.6 ± 2.7 cm2, p < 0.05); and in the VM (18.2 ± 6.3 cm2 and 13.4 ± 3. 4 cm2, p < 0.05). In addition, the anterior-posterior (AP) diameters of the hiatus on VM were significantly increased in the IR group (40.0 ± 4.7 mm and 33.0 ± 4.4 mm, p < 0.05). With insulin levels as the dependent variable, multivariate regression analysis shows that insulin levels were significantly correlated with the levator hiatus area on VM (p < 0.05) and waist circumference (p < 0.05). The pelvic organ descent on VM in the IR group was significant (p < 0.05). CONCLUSIONS: The areas of resting state levator hiatus and on VM were significantly larger in the IR than that in the control groups. In addition, the position of the pelvic organ on VM in the IR group was significantly descended. The insulin levels were correlated with the pelvic floor muscle function.
With regard to insulin resistance and pelvic floor function, previous studies focused on the role of polycystic ovaries, metabolic syndrome, and pelvic prolapse. The use of ultrasound can improve understanding of the static, dynamic and organ prolapse conditions. This study aimed to assess pelvic floor muscle function in non-diabetic women with insulin resistance, a condition where the body uses insulin less effectively. A total of 216 women with insulin resistance and 118 without it were examined using 3D ultrasound during rest and while performing the Valsalva manoeuvre. Our results show that the pelvic floor muscles had extra space between them and moved differently in women with insulin resistance than in those without the condition. This suggests that insulin resistance may affect function of pelvic floor muscles to cause adverse consequences.
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Imagenología Tridimensional , Resistencia a la Insulina , Diafragma Pélvico , Ultrasonografía , Humanos , Femenino , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/fisiopatología , Ultrasonografía/métodos , Adulto , Persona de Mediana Edad , Estudios de Casos y Controles , Insulina/sangre , Maniobra de Valsalva/fisiologíaRESUMEN
CCT MOTIF FAMILY (CMF) genes belong to the CCT gene family and have been shown to play a role in diverse processes, such as flowering time and yield regulation, as well as responses to abiotic stresses. CMF genes have not yet been identified in Brassica rapa. A total of 25 BrCMF genes were identified in this study, and these genes were distributed across eight chromosomes. Collinearity analysis revealed that B. rapa and Arabidopsis thaliana share many homologous genes, suggesting that these genes have similar functions. According to sequencing analysis of promoters, several elements are involved in regulating the expression of genes that mediate responses to abiotic stresses. Analysis of the tissue-specific expression of BrCMF14 revealed that it is highly expressed in several organs. The expression of BrCMF22 was significantly downregulated under salt stress, while the expression of BrCMF5, BrCMF7, and BrCMF21 was also significantly reduced under cold stress. The expression of BrCMF14 and BrCMF5 was significantly increased under drought stress, and the expression of BrCMF7 was upregulated. Furthermore, protein-protein interaction network analysis revealed that A. thaliana homologs of BrCMF interacted with genes involved in the abiotic stress response. In conclusion, BrCMF5, BrCMF7, BrCMF14, BrCMF21, and BrCMF22 appear to play a role in responses to abiotic stresses. The results of this study will aid future investigations of CCT genes in B. rapa.
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BACKGROUND: MRI-based placental analyses have been used to improve fetal growth restriction (FGR) assessment by complementing ultrasound-based measurements. However, these are still limited by time-consuming manual annotation in MRI data and the lack of mother-based information. PURPOSE: To develop and validate a hybrid model for accurate FGR assessment by automatic placental radiomics on T2-weighted imaging (T2WI) and multifeature fusion. STUDY TYPE: Retrospective. POPULATION: 274 pregnant women (29.5 ± $$ \pm $$ 4.0 years) from two centers were included and randomly divided into training (N = 119), internal test (N = 40), time-independent validation (N = 43), and external validation (N = 72) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, T2WI half-Fourier acquisition single-shot turbo spin-echo pulse sequence. ASSESSMENT: First, the placentas on T2WI were manually annotated, and a deep learning model was developed to automatically segment the placentas. Then, the radiomic features were extracted from the placentas and selected by three-step feature selection. In addition, fetus-based measurement features and mother-based clinical features were obtained from ultrasound examinations and medical records, respectively. Finally, a hybrid model based on random forest was constructed by fusing these features, and further compared with models based on other machine learning methods and different feature combinations. STATISTICAL TESTS: The performances of placenta segmentation and FGR assessment were evaluated by Dice similarity coefficient (DSC) and the area under the receiver operating characteristic curve (AUROC), respectively. A P-value <0.05 was considered statistically significant. RESULTS: The placentas were automatically segmented with an average DSC of 90.0%. The hybrid model achieved an AUROC of 0.923, 0.931, and 0.880 on the internal test, time-independent validation, and external validation sets, respectively. The mother-based clinical features resulted in significant performance improvements for FGR assessment. DATA CONCLUSION: The proposed hybrid model may be able to assess FGR with high accuracy. Furthermore, information complementation based on placental, fetal, and maternal features could also lead to better FGR assessment performance. TECHNICAL EFFICACY: Stage 2.
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Guanine nucleotide-exchange factors (GEFs) genes play key roles in plant root and pollen tube growth, phytohormone responses, and abiotic stress responses. RopGEF genes in Brassica rapa have not yet been explored. Here, GEF genes were found to be distributed across eight chromosomes in B. rapa and were classified into three subfamilies. Promoter sequence analysis of BrRopGEFs revealed the presence of cis-elements characteristic of BrRopGEF promoters, and these cis-elements play a role in regulating abiotic stress tolerance and stress-related hormone responses. Organ-specific expression profiling demonstrated that BrRopGEFs were ubiquitously expressed in all organs, especially the roots, suggesting that they play a role in diverse biological processes. Gene expression analysis revealed that the expression of BrRopGEF13 was significantly up-regulated under osmotic stress and salt stress. RT-qPCR analysis revealed that the expression of BrRopGEF13 was significantly down-regulated under various types of abiotic stress. Protein-protein interaction (PPI) network analysis revealed interactions between RopGEF11, the homolog of BrRopGEF9, and the VPS34 protein in Arabidopsis thaliana, as well as interactions between AtRopGEF1, the homolog of BrRopGEF13 in Arabidopsis, and the ABI1, HAB1, PP2CA, and CPK4 proteins. VPS34, ABI1, HAB1, PP2CA, and CPK4 have previously been shown to confer resistance to unfavorable environments. Overall, our findings suggest that BrRopGEF9 and BrRopGEF13 play significant roles in regulating abiotic stress tolerance. These findings will aid future studies aimed at clarifying the functional characteristics of BrRopGEFs.
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Brassica rapa , Brassica rapa/metabolismo , Estrés Fisiológico/genética , Estrés Salino , Familia de Multigenes , Perfilación de la Expresión Génica , Filogenia , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is a prevalent malignant tumor typically treated through surgical removal. However, when the lesion is situated in specific areas like the hands, feet, or lips, particularly if it's sizable, surgical interventions can adversely impact appearance and function. In such cases, non-surgical treatments are preferable to preserve both aesthetics and functionality. We present a case of recurrent cSCC on the plantar region post-surgery. Given the extensive lesion area, deep infiltration, and the patient's reliance on foot function, hematoporphyrin derivative-photodynamic therapy (HpD-PDT) was chosen over traditional surgery. The lesion was successfully treated, and while a minor recurrence was observed after 20 months, it was localized and amenable to non-surgical intervention. We posit that HpD-PDT is a viable treatment for cSCC, especially in unique locations, with extensive lesions, and postoperative recurrence.
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Carcinoma de Células Escamosas , Fotoquimioterapia , Neoplasias Cutáneas , Humanos , Derivado de la Hematoporfirina/uso terapéutico , Fotoquimioterapia/métodos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
The AT-hook motif nuclear localized (AHL) gene family is a highly conserved transcription factor critical for the growth, development, and stress tolerance of plants. However, the function of the AHL gene family in Brassica rapa (B. rapa) remains unclear. In this study, 42 AHL family members were identified from the B. rapa genome and mapped to nine B. rapa chromosomes. Two clades have formed in the evolution of the AHL gene family. The results showed that most products encoded by AHL family genes are located in the nucleus. Gene duplication was common and expanded the BrAHL gene family. According to the analysis of cis-regulatory elements, the genes interact with stress responses (osmotic, cold, and heavy metal stress), major hormones (abscisic acid), and light responses. In addition, the expression profiles revealed that BrAHL genes are widely expressed in different tissues. BrAHL16 was upregulated at 4 h under drought stress, highly expressed under cadmium conditions, and downregulated in response to cold conditions. BrAHL02 and BrAHL24 were upregulated at the initial time point and peaked at 12 h under cold and cadmium stress, respectively. Notably, the interactions between AHL genes and proteins under drought, cold, and heavy metal stresses were observed when predicting the protein-protein interaction network.
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Brassica rapa , Brassica rapa/metabolismo , Genes de Plantas , Perfilación de la Expresión Génica , Cadmio/metabolismo , Genoma de Planta , Estrés Fisiológico/genética , Filogenia , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Nitrate transporter 2 (NRT2) proteins play vital roles in both nitrate (NO3-) uptake and translocation as well as abiotic stress responses in plants. However, little is known about the NRT2 gene family in Brassica rapa. In this study, 14 NRT2s were identified in the B. rapa genome. The BrNRT2 family members contain the PLN00028 and MATE_like superfamily domains. Cis-element analysis indicated that regulatory elements related to stress responses are abundant in the promoter sequences of BrNRT2 genes. BrNRT2.3 expression was increased after drought stress, and BrNRT2.1 and BrNRT2.8 expression were significantly upregulated after salt stress. Furthermore, protein interaction predictions suggested that homologs of BrNRT2.3, BrNRT2.1, and BrNRT2.8 in Arabidopsis thaliana may interact with the known stress-regulating proteins AtNRT1.1, AtNRT1.5, and AtNRT1.8. In conclusion, we suggest that BrNRT2.1, BrNRT2.3, and BrNRT2.8 have the greatest potential for inducing abiotic stress tolerance. Our findings will aid future studies of the biological functions of BrNRT2 family genes.
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Arabidopsis , Brassica rapa , Brassica rapa/genética , Transportadores de Nitrato , Estrés Salino , Arabidopsis/genética , Transporte BiológicoRESUMEN
BACKGROUND: Hypoxia contributes to the development of invasive and metastatic cancer cells, and is detrimental to cancer treatment. This study aimed to explore the molecular mechanisms by which hypoxic microenvironments affect hypoxic non-small cell lung cancer (NSCLC) development and the effects of M2 macrophage-derived extracellular vesicles (EVs) on NSCLC cells. METHODS: A549 cells were cultured in an anoxic incubator for 48 h to construct hypoxic A549 cells, and then normal and hypoxic A549 cells were harvested for RNA sequencing. Next, THP-1 cells were used to induce M2 macrophages, and EVs were isolated from THP-1 cells and M2 macrophages. Cell counting kit-8 and transwell assays were used to determine the viability and migration of hypoxic A549 cells, respectively. RESULTS: After sequencing, 2426 DElncRNAs and 501 DEmiRNAs were identified in normal A549 cells and hypoxic A549 cells. These DElncRNAs and DEmiRNAs were significantly enriched in "Wnt signaling pathway," "Hippo signaling pathway," "Rap1 signaling pathway," "calcium signaling pathway," "mTOR signaling pathway," and "TNF signaling pathway." Subsequently, ceRNA networks consisting of 4 lncRNA NDRG1 transcripts, 16 miRNAs and 221 target mRNAs were built, and the genes in the ceRNA networks were significantly associated with "Hippo signaling pathway" and "HIF-1 signaling pathway." EVs were successfully extracted from THP-1 cells and M2 macrophages, and M2 macrophage-derived EVs significantly enhanced the viability and migration of hypoxic A549 cells. Finally, M2 macrophage-derived EVs further upregulated the expression of NDRG1-009, NDRG1-006, VEGFA, and EGLN3, while downregulating miR-34c-5p, miR-346, and miR-205-5p in hypoxic A549 cells. CONCLUSIONS: M2 macrophage-derived EVs may worsen the progression of NSCLC in a hypoxic microenvironment by regulating the NDRG1-009-miR-34c-5p-VEGFA, NDRG1-006-miR-346-EGLN3, NDRG1-009-miR-205-5p-VEGFA, and Hippo/HIF-1 signaling pathways.
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Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Hipoxia , Microambiente TumoralRESUMEN
BACKGROUND: Early pregnancy loss (EPL) or spontaneous loss of an intrauterine pregnancy within the first trimester occurs commonly worldwide. It is useful to predict the possibility of fetal chromosomal abnormalities using other cheap and easily available markers. OBJECTIVE: This study aimed to evaluate whether the uterine artery pulsatility index (UtA-PI) can predict fetal chromosomal abnormality in early pregnancy loss (EPL). METHODS: This was a retrospective cohort study including 148 women who underwent dilation and curettage for missed abortion. The UtA-PI was measured and evaluated by transvaginal ultrasound. Abnormal UtA-PI was identified through the mean of left and right UA-PI ≥ 90th percentiles of the relevant values for the corresponding gestational age. Copy number variation sequencing (CNV-seq) was performed on EPL cases without maternal cell contamination. RESULTS: 107 (72.3%) cases were classified with normal UtA-PI, while 41 (27.7%) cases were classified with abnormal UtA-PI. The fetal chromosomal abnormality rate was significantly higher in cases with normal UtA-PI than in those with abnormal UtA-PI (67.3% vs 22.0%, P = 7.1 × 10-7). Compared to cases with abnormal UtA-PI, the risk of fetal chromosomal abnormalities in cases with normal UtA-PI increased with an odds ratio of 7.3 (95% confidence interval [CI]: 3.2â17.0, P = 4 × 10-7). The predictive value of normal UtA-PI alone for fetal chromosomal abnormalities was shown to have an area under the curve of 0.67â0.71 in our population. CONCLUSION: The UtA-PI seems to be lower and less likely to be elevated in EPL with fetal chromosomal abnormalities compared to those without aneuploidies. We suggest that UtA-PI should be examined in all EPL patients.
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The ASYMMETRIC LEAVES2/LATERAL ORGAN BOUNDARIES (AS2/LOB) gene family plays a pivotal role in plant growth, induction of phytohormones, and the abiotic stress response. However, the AS2 gene family in Brassica rapa has yet to be investigated. In this study, we identified 62 AS2 genes in the B. rapa genome, which were classified into six subfamilies and distributed across 10 chromosomes. Sequence analysis of BrAS2 promotors showed that there are several typical cis-elements involved in abiotic stress tolerance and stress-related hormone response. Tissue-specific expression analysis showed that BrAS2-47 exhibited ubiquitous expression in all tissues, indicating it may be involved in many biological processes. Gene expression analysis showed that the expressions of BrAS2-47 and BrAS2-10 were significantly downregulated under cold stress, heat stress, drought stress, and salt stress, while BrAS2-58 expression was significantly upregulated under heat stress. RT-qPCR also confirmed that the expression of BrAS2-47 and BrAS2-10 was significantly downregulated under cold stress, drought stress, and salt stress, and in addition BrAS2-56 and BrAS2-4 also changed significantly under the three stresses. In addition, protein-protein interaction (PPI) network analysis revealed that the Arabidopsis thaliana genes AT5G67420 (homologous gene of BrAS2-47 and BrAS2-10) and AT3G49940 (homologous gene of BrAS2-58) can interact with NIN-like protein 7 (NLP7), which has been previously reported to play a role in resistance to adverse environments. In summary, our findings suggest that among the BrAS2 gene family, BrAS2-47 and BrAS2-10 have the most potential for the regulation of abiotic stress tolerance. These results will facilitate future functional investigations of BrAS2 genes in B. rapa.
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Arabidopsis , Brassica rapa , Brassica rapa/metabolismo , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Genoma de Planta , Perfilación de la Expresión Génica , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , FilogeniaRESUMEN
With the fast development of AI technologies, deep learning is widely applied for biomedical data analytics and digital healthcare. However, there remain gaps between AI-aided diagnosis and real-world healthcare demands. For example, hemodynamic parameters of the middle cerebral artery (MCA) have significant clinical value for diagnosing adverse perinatal results. Nevertheless, the current measurement procedure is tedious for sonographers. To reduce the workload of sonographers, we propose MCAS-GP, a deep learning-empowered framework that tackles the Middle Cerebral Artery Segmentation and Gate Proposition. MCAS-GP can automatically segment the region of the MCA and detect the corresponding position of the gate in the procedure of fetal MCA Doppler assessment. In MCAS-GP, a novel learnable atrous spatial pyramid pooling (LASPP) module is designed to adaptively learn multi-scale features. We also propose a novel evaluation metric, Affiliation Index, for measuring the effectiveness of the position of the output gate. To evaluate our proposed MCAS-GP, we build a large-scale MCA dataset, collaborating with the International Peace Maternity and Child Health Hospital of China welfare institute (IPMCH). Extensive experiments on the MCA dataset and two other public surgical datasets demonstrate that MCAS-GP can achieve considerable performance improvement in both accuracy and inference time.
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OBJECTIVES: To assess the cost-effectiveness of Arg16Gly ADRB2 pharmacogenomic testing compared with no Arg16Gly ADRB2 testing to guide the use of long-acting ß2 receptor agonist (LABA) in asthma patients aged 1 to 5 years in China. METHODS: This economic evaluation developed a Markov model with four health states (no exacerbation, mild exacerbation, moderate-to-severe exacerbation, and death). Transition probabilities were estimated from the rate of exacerbations, the case-fatality rate of patients hospitalized for exacerbations, and natural mortality. Costs included drug costs and exacerbation management costs. Cost inputs and utilities for each health state were gained from public databases and the literatures. Costs and quality-adjusted life years (QALYs) were estimated for ten years. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, in contrast to the group without the genotype test, the incremental total cost was -¥334.7, and the incremental QALY was 0.001 in the Arg16Gly ADRB2 genotyping group. Therefore, the Arg16Gly ADRB2 test group was the dominant strategy for children with asthma in China. The sensitivity analyses showed that the model was relatively stable. CONCLUSION: Arg16Gly ADRB2 testing before using LABA is a cost-effective approach compared with no gene testing for pediatric asthma.
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Asma , Farmacogenética , Niño , Humanos , Análisis Costo-Beneficio , Asma/tratamiento farmacológico , Asma/genética , Costos de los Medicamentos , Quimioterapia Combinada , Años de Vida Ajustados por Calidad de Vida , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/uso terapéuticoRESUMEN
Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.
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Quitosano , Neoplasias , Humanos , Inmunoterapia , Proteínas de la Membrana , Neoplasias/tratamiento farmacológico , Terapia Fototérmica , Especies Reactivas de Oxígeno , Microambiente TumoralRESUMEN
Heavy metal-associated proteins (HMPs) participate in heavy metal detoxification. Although HMPs have been identified in several plants, no studies to date have identified the HMPs in Brassica rapa (B. rapa). Here, we identified 85 potential HMPs in B. rapa by bioinformatic methods. The promoters of the identified genes contain many elements associated with stress responses, including response to abscisic acid, low-temperature, and methyl jasmonate. The expression levels of BrHMP14, BrHMP16, BrHMP32, BrHMP41, and BrHMP42 were upregulated under Cu2+, Cd2+, Zn2+, and Pb2+ stresses. BrHMP06, BrHMP30, and BrHMP41 were also significantly upregulated after drought treatment. The transcripts of BrHMP06 and BrHMP11 increased mostly under cold stress. After applying salt stress, the expression of BrHMP02, BrHMP16, and BrHMP78 was induced. We observed increased BrHMP36 expression during the self-incompatibility (SI) response and decreased expression in the compatible pollination (CP) response during pollen-stigma interactions. These changes in expression suggest functions for these genes in HMPs include participating in heavy metal transport, detoxification, and response to abiotic stresses, with the potential for functions in sexual reproduction. We found potential co-functional partners of these key players by protein-protein interaction (PPI) analysis and found that some of the predicted protein partners are known to be involved in corresponding stress responses. Finally, phosphorylation investigation revealed many phosphorylation sites in BrHMPs, suggesting post-translational modification may occur during the BrHMP-mediated stress response. This comprehensive analysis provides important clues for the study of the molecular mechanisms of BrHMP genes in B. rapa, especially for abiotic stress and pollen-stigma interactions.
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Brassica rapa , Brassica rapa/genética , Brassica rapa/metabolismo , Polinización , Estrés Fisiológico/genética , Estrés Salino , PolenRESUMEN
OBJECTIVE: This study aimed to determine whether the combination of pregnancy-associated endothelial cell-specific molecule 1 (ESM-1), the placental growth factor (PLGF) in the first- and second-trimester maternal serum, and the uterine artery Doppler pulsatility index (PI) in the second trimester can predict preeclampsia (PE). METHODS: The serum levels of ESM-1 and PLGF in 33 severe preeclampsia (SPE) patients, 18 mild preeclampsia patients (MPE), and 60 age-matched normal controls (CON) were measured. The Doppler ultrasonography was performed, and the artery pulsatility index (PI) was calculated for the same subjects. RESULTS: The 2nd PLGF level was significantly lower and the 2nd PI was higher than those in the MPE group. Combining the 2nd PLGF with the 2nd PI yielded an AUC of 0.819 (83.33% sensitivity and 70.00% specificity). In the SPE group, the 1st ESM-1 level and the 2nd PLGF level were significantly lower, and the 2nd ESM-1 level and the 2nd PI were significantly higher in the SPE group. The combination of the 1st ESM-1, the 2nd PLGF, and the 2nd PI yielded an AUC of 0.912 (72.73% sensitivity and 95.00% specificity). CONCLUSIONS: The 1st ESM-1 and the 2nd PLGF levels and the 2nd PI were associated with PE. The combination of serum biomarkers and the PI improved the screening efficiency of the PE prediction, especially for SPE.
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Flowering plants have evolved numerous intraspecific and interspecific prezygotic reproductive barriers to prevent production of unfavourable offspring1. Within a species, self-incompatibility (SI) is a widely utilized mechanism that rejects self-pollen2,3 to avoid inbreeding depression. Interspecific barriers restrain breeding between species and often follow the SI × self-compatible (SC) rule, that is, interspecific pollen is unilaterally incompatible (UI) on SI pistils but unilaterally compatible (UC) on SC pistils1,4-6. The molecular mechanisms underlying SI, UI, SC and UC and their interconnections in the Brassicaceae remain unclear. Here we demonstrate that the SI pollen determinant S-locus cysteine-rich protein/S-locus protein 11 (SCR/SP11)2,3 or a signal from UI pollen binds to the SI female determinant S-locus receptor kinase (SRK)2,3, recruits FERONIA (FER)7-9 and activates FER-mediated reactive oxygen species production in SI stigmas10,11 to reject incompatible pollen. For compatible responses, diverged pollen coat protein B-class12-14 from SC and UC pollen differentially trigger nitric oxide, nitrosate FER to suppress reactive oxygen species in SC stigmas to facilitate pollen growth in an intraspecies-preferential manner, maintaining species integrity. Our results show that SRK and FER integrate mechanisms underlying intraspecific and interspecific barriers and offer paths to achieve distant breeding in Brassicaceae crops.
Asunto(s)
Brassicaceae , Flores , Hibridación Genética , Proteínas de Plantas , Polinización , Brassicaceae/genética , Brassicaceae/metabolismo , Depresión Endogámica , Óxido Nítrico/metabolismo , Fosfotransferasas/metabolismo , Fitomejoramiento , Proteínas de Plantas/metabolismo , Polen/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Especificidad de la Especie , Flores/metabolismo , AutofecundaciónRESUMEN
Ovarian granulosa cell tumor (OGCT) is a relatively rare ovarian tumor originating from ovarian sex cord-stromal cells. It is generally believed that the tumor is mainly a solid mass in the early stage, and with the volume increasing, the tumor would undergo multiple cystic changes. But few such cases have been reported. This article reports a case of transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in 2 months on MR imaging in an adult woman. In this case, a 55-year-old postmenopausal woman underwent MR imaging for irregular vaginal bleeding in March 2022, during which a 6-cm cystic-solid mass was detected in the right ovary with iso-hypo intensity on T1WI, iso-hyper intensity on T2WI, and hyper intensity on DWI. After injection of the contrast medium, the mass displayed progressive and obvious enhancement, which was diagnosed as OGCT. Due to the COVID-19 pandemic, the patient was unable to receive surgery in time. Two months later, the patient returned to the hospital and underwent MRI again, when a 20-cm cyst mass was detected in the pelvis, which contained little solid component at the edge. The patient was admitted and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The postoperative pathology confirmed the diagnosis of adult type stage IC1 OGCT. This finding may be precious in that it could help understand the initiation and progression of OGCT.