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1.
Plant Physiol ; 195(3): 2309-2322, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38466216

RESUMEN

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.


Asunto(s)
Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Ácido Abscísico/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Transducción de Señal , Meristema/genética , Meristema/crecimiento & desarrollo , Meristema/metabolismo , Reproducción , Mutación/genética , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/genética , Proteínas de Homeodominio
2.
Plant Mol Biol ; 114(3): 37, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602592

RESUMEN

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.


Asunto(s)
Nitratos , Setaria (Planta) , Especies Reactivas de Oxígeno , Nitratos/farmacología , Setaria (Planta)/genética , Peróxido de Hidrógeno , Cloruro de Sodio , Oxígeno , Transducción de Señal , Perfilación de la Expresión Génica , Nitrógeno
3.
Lab Invest ; 104(5): 102044, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38452903

RESUMEN

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.


Asunto(s)
Enfermedades Pulmonares , Transducción de Señal , Sirtuina 1 , Humanos , Sirtuina 1/metabolismo , Enfermedades Pulmonares/metabolismo , Animales , Envejecimiento/metabolismo , Envejecimiento/fisiología
4.
Plant Physiol ; 194(1): 391-407, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37738410

RESUMEN

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Plantones/metabolismo , Cotiledón/metabolismo , Etiolado , Glucosa/metabolismo , Luz , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fitocromo A/metabolismo , Regulación de la Expresión Génica de las Plantas
5.
Mutagenesis ; 39(2): 141-145, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38150355

RESUMEN

OBJECTIVE: Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. METHODS: CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. RESULTS: CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. CONCLUSION: Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.


Asunto(s)
Neoplasias de la Mama , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , Animales , Ratones , Neoplasias del Cuello Uterino/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Línea Celular Tumoral , Ratones Desnudos , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
6.
Inorg Chem ; 63(14): 6276-6284, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38546717

RESUMEN

Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B11k- (M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B112- boron-wheel complex has an unprecedented D11h point-group symmetry. The remarkable stability of the planar Y©B112- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B112- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.

7.
Int J Phytoremediation ; : 1-11, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38932483

RESUMEN

Urease-producing bacteria (UPB) are widely present in soil and play an important role in soil ecosystems. In this study, 65 UPB strains were isolated from cadmium (Cd)-polluted soil around a lead-zinc mine in Yunnan Province, China. The Cd tolerance, removal of Cd from aqueous solution, production of indoleacetic acid (IAA) and plant growth-promoting effects of these materials were investigated. The results indicate that among the 65 UPB strains, four strains with IAA-producing ability were screened and identified as Bacillus thuringiensis W6-11, B. cereus C7-4, Serratia marcescens W11-10, and S. marcescens C5-6. Among the four strains, B. cereus C7-4 had the highest Cd tolerance, median effect concentration (EC50) of 59.94 mg/L. Under Cd 5 mg/L, S. marcescens C5-6 had the highest Cd removal from aqueous solution, up to 69.83%. Under Cd 25 mg/kg, inoculation with B. cereus C7-4 significantly promoted maize growth in a sand pot by increasing the root volume, root surface area, and number of root branches by 22%, 29%, and 20%, respectively, and plant height and biomass by 16% and 36%, respectively, and significantly increasing Cd uptake in the maize roots. Therefore, UPB is a potential resource for enhancing plant adaptability to Cd stress in plants with Cd-polluted habitats.


This study utilized urease-producing bacteria screened from the soil of lead zinc mining areas in Yunnan, China as the research object, enriching the microbial resources in Yunnan. In addition, this article verified the IAA production ability and cadmium removal ability of urease-producing bacteria, and screened out bifunctional urease-producing bacteria that have potential in cadmium pollution control and plant growth promotion.

8.
Int J Mol Sci ; 25(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892157

RESUMEN

A dual-emission ratio-fluorescent sensing nanohybrid based on Radix Hedysari green-synthesized carbon quantum dots (CDs) and glutathione-functionalized gold nanoclusters (GSH-AuNCs) had been developed for the determination of cefodizime sodium (CDZM). The designed fluorescence nanohybrid had two significant fluorescence emission peaks at 458 nm and 569 nm when excited at 360 nm, which was attributed to the CDs and GSH-AuNCs. With the addition of CDZM, the fluorescence at 458 nm was slightly weakened while the fluorescence at 569 nm was enhanced obviously. Based on the relationship between the I569/I458 fluorescence intensity ratio and the concentration of CDZM, the designed nanohybrid exhibited a good linearity range of 1.0-1000.0 µM and the limit of detection (LOD) was 0.19 µM. The method was finally applied in the detection of CDZM in urine, showing the potential applications in complicated biological samples.


Asunto(s)
Glutatión , Oro , Nanopartículas del Metal , Puntos Cuánticos , Puntos Cuánticos/química , Humanos , Oro/química , Nanopartículas del Metal/química , Glutatión/orina , Glutatión/química , Límite de Detección , Espectrometría de Fluorescencia/métodos , Carbono/química , Cefalosporinas/orina , Cefalosporinas/química , Fluorescencia
9.
BMC Oral Health ; 24(1): 500, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724912

RESUMEN

BACKGROUND: Teeth identification has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. Accurately identifying teeth is a vital aspect of dental education and clinical practice, but can be challenging due to the anatomical similarities between categories. In this study, we aim to explore the possibility of using a deep learning model to classify isolated tooth by a set of photographs. METHODS: A collection of 5,100 photographs from 850 isolated human tooth specimens were assembled to serve as the dataset for this study. Each tooth was carefully labeled during the data collection phase through direct observation. We developed a deep learning model that incorporates the state-of-the-art feature extractor and attention mechanism to classify each tooth based on a set of 6 photographs captured from multiple angles. To increase the validity of model evaluation, a voting-based strategy was applied to refine the test set to generate a more reliable label, and the model was evaluated under different types of classification granularities. RESULTS: This deep learning model achieved top-3 accuracies of over 90% in all classification types, with an average AUC of 0.95. The Cohen's Kappa demonstrated good agreement between model prediction and the test set. CONCLUSIONS: This deep learning model can achieve performance comparable to that of human experts and has the potential to become a valuable tool for dental education and various applications in accurately identifying isolated tooth.


Asunto(s)
Aprendizaje Profundo , Diente , Humanos , Diente/anatomía & histología , Diente/diagnóstico por imagen , Fotografía Dental/métodos
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 553-558, 2024 Jun 15.
Artículo en Zh | MEDLINE | ID: mdl-38926370

RESUMEN

The prevalence of short stature among prepubertal children in China is relatively high. Early identification of the cause and timely intervention can bring greater benefits to children with short stature. This paper provides an overview of early diagnosis, intervention measures, and personalized medication dosage for prepubertal short stature children, aiming to provide references for clinical doctors.


Asunto(s)
Estatura , Diagnóstico Precoz , Humanos , Niño , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/etiología
11.
J Physiol ; 601(16): 3631-3645, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37401732

RESUMEN

Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function, which is associated with an increased risk of adult-onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex-dependent manner. RT-qPCR analysis of miR-29a/c-3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) pregnancies and PE. Bioinformatic analysis of an RNA-seq dataset was performed to identify PE-dysregulated miR-29a/c-3p target genes in female and male P0-HUVECs. Gain- and loss-of-function assays were conducted to determine the effects of miR-29a/c-3p on endothelial monolayer integrity and proliferation in response to transforming growth factor-ß1 (TGFß1) and tumour necrosis factor-α (TNFα) in NT and PE HUVECs at passage 1. We observed that PE downregulated miR-29a/c-3p in male and female P0-HUVECs. PE dysregulated significantly more miR-29a/c-3p target genes in female vs. male P0-HUVECs. Many of these PE-differentially dysregulated miR-29a/c-3p target genes are associated with critical cardiovascular diseases and endothelial function. We further demonstrated that miR-29a/c-3p knockdown specifically recovered the PE-abolished TGFß1-induced strengthening of endothelial monolayer integrity in female HUVECs, while miR-29a/c-3p overexpression specifically enhanced the TNFα-promoted cell proliferation in male PE HUVECs. In conclusion, PE downregulates miR-29a/c-3p expression and differentially dysregulates miR-29a/c-3p target genes associated with cardiovascular diseases and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex-specific endothelial dysfunction observed in PE. KEY POINTS: Preeclampsia differentially impairs female and male fetal endothelial cell function in responses to cytokines. Pro-inflammatory cytokines are elevated in maternal circulation during pregnancy in preeclampsia. MicroRNAs are critical regulators of endothelial cell function during pregnancy. We have previously reported that preeclampsia downregulated microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in primary fetal endothelial cells. However, it is unknown if PE differentially dysregulates the expression of miR-29a/c-3p in female and male fetal endothelial cells. We show that preeclampsia downregulates miR-29a/c-3p in male and female HUVECs and preeclampsia dysregulates cardiovascular disease- and endothelial function-associated miR-29a/c-3p target genes in HUVECs in a fetal sex-specific manner. MiR-29a/c-3p differentially mediate cell responses to cytokines in female and male fetal endothelial cells from preeclampsia. We have revealed fetal sex-specific dysregulation of miR-29a/c-3p target genes in fetal endothelial cells from preeclampsia. This differential dysregulation may contribute to fetal sex-specific endothelial dysfunction in offspring born to preeclamptic mothers.


Asunto(s)
Enfermedades Cardiovasculares , MicroARNs , Preeclampsia , Enfermedades Vasculares , Adulto , Embarazo , Niño , Humanos , Masculino , Femenino , Preeclampsia/genética , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedades Cardiovasculares/metabolismo , Citocinas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Enfermedades Vasculares/metabolismo
12.
J Am Chem Soc ; 145(36): 19440-19457, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37643971

RESUMEN

The utilization of carboranes in supramolecular chemistry has attracted considerable attention. The unique spatial configuration and weak interaction forces of carboranes can help to explore the properties of supramolecular complexes, particularly via host-guest chemistry. Additionally, certain difficulties encountered in carborane development─such as controlled B-H bond activation─can be overcome by judiciously selecting metal centers and their adjacent ligands. However, few studies are being conducted in this nascent research area. With advances in this field, novel carborane-based supramolecular complexes will likely be prepared, structurally characterized, and intrinsically investigated. To expedite these efforts, we present major findings from recent studies, including π-π interactions, host-guest associations, and steric effects, which have been leveraged to implement a regioselective process for activating B(2,9)-, B(2,8)-, and B(2,7)-H bonds of para-carboranes and B(4,7)-H bonds of ortho-carboranes. Future studies should clarify the unique weak interactions of carboranes and their potential for enhancing the utility of supramolecular complexes. Although carboranes exhibit several unique weak interactions (such as dihydrogen-bond [Bδ+-Hδ-···Hδ+-Cδ-], Bδ+-Hδ-···M+, and Bδ+-Hδ-···π interactions), the manner in which they can be utilized remains unclear. Supramolecular complexes, particularly those based on host-guest chemistry, can be utilized as a platform for demonstrating potential applications of these weak interactions. Owing to the importance of alkane separation, applications related to the recognition and separation of alkane isomers via dihydrogen-bond interactions are primarily summarized. Advances in the research of unique weak interactions in carboranes will certainly lead to more possibilities for supramolecular chemistry.

13.
J Am Chem Soc ; 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37022992

RESUMEN

Developing novel assembly methods for supramolecular compounds has long been a research challenge. Herein, we describe how to integrate the B-C coupling reaction and "cage walking" process into coordination self-assembly to construct supramolecular cages. In this strategy, dipyridine linkers containing alkynes react with the metallized carborane backbone through B-C coupling and then "cage walking" resulting in metallacages. However, dipyridine linkers without alkynyl groups can form only metallacycles. We can regulate the size of metallacages based on the length of the alkynyl bipyridine linkers. When tridentate-pyridine linkers participate in this reaction, a new type of ravel is formed. The metallization of carboranes, the B-C coupling reaction, and especially the "cage walking" process of carborane cages play a vital role in this reaction. This work provides a promising principle for the synthesis of metallacages and opens up a novel opportunity in the supramolecular field.

14.
Eur J Neurosci ; 57(5): 739-761, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36656174

RESUMEN

Increasing evidence suggests that astrocytes play an important role in the progression of Parkinson's disease (PD). Previous studies on our parkin knockout mouse demonstrated a higher accumulation of damaged mitochondria in astrocytes than in surrounding dopaminergic (DA) neurons, suggesting that Parkin plays a crucial role regarding their interaction during PD pathogenesis. In the current study, we examined primary mesencephalic astrocytes and neurons in a direct co-culture system and discovered that the parkin deletion causes an impaired differentiation of mesencephalic neurons. This effect required the parkin mutation in astrocytes as well as in neurons. In Valinomycin-treated parkin-deficient astrocytes, ubiquitination of Mitofusin 2 was abolished, whereas there was no significant degradation of the outer mitochondrial membrane protein Tom70. This result may explain the accumulation of damaged mitochondria in parkin-deficient astrocytes. We examined differential gene expression in the substantia nigra region of our parkin-KO mouse by RNA sequencing and identified an upregulation of the endoplasmic reticulum (ER) Ca2+ -binding protein reticulocalbin 1 (RCN1) expression, which was validated using qPCR. Immunostaining of the SN brain region revealed RCN1 expression mainly in astrocytes. Our subcellular fractionation of brain extract has shown that RCN1 is located in the ER and in mitochondria-associated membranes (MAM). Moreover, a loss of Parkin function reduced ATP-stimulated calcium-release in ER mesencephalic astrocytes that could be attenuated by siRNA-mediated RCN1 knockdown. Our results indicate that RCN1 plays an important role in ER-associated calcium dyshomeostasis caused by the loss of Parkin function in mesencephalic astrocytes, thereby highlighting the relevance of astrocyte function in PD pathomechanisms.


Asunto(s)
Calcio , Retículo Endoplásmico , Enfermedad de Parkinson , Ubiquitina-Proteína Ligasas , Animales , Ratones , Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Neuronas Dopaminérgicas/metabolismo , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Ratones Noqueados , Enfermedad de Parkinson/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Regulación hacia Arriba
15.
Anal Chem ; 95(12): 5256-5266, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36917632

RESUMEN

Myxobacteria are fascinating prokaryotes featuring a potent capacity for producing a wealth of bioactive molecules with intricate chemical topology as well as intriguing enzymology, and thus it is critical to developing an efficient pipeline for bioprospecting. Herein, we construct the database MyxoDB, the first public compendium solely dedicated to myxobacteria, which enabled us to provide an overview of the structural diversity and taxonomic distribution of known myxobacterial natural products. Moreover, we demonstrated that the cutting-edge NMR-based metabolomics was effective to differentiate the biosynthetic priority of myxobacteria, whereby MyxoDB could greatly streamline the dereplication of multifarious known compounds and accordingly speed up the discovery of new compounds. This led to the rapid identification of a class of linear di-lipopeptides (archangimins) and a rare rearranged sterol (corasterol) that were endowed with unique chemical architectures and/or biosynthetic enzymology. We also showcased that NMR-based metabolomics, MyxoDB, and genomics can also work concertedly to accelerate the targeted discovery of a polyketidic compound pyxipyrrolone C. All in all, this study sets the stage for the discovery of many more novel natural products from underexplored myxobacterial resources.


Asunto(s)
Productos Biológicos , Myxococcales , Productos Biológicos/química , Bioprospección , Imagen por Resonancia Magnética , Metabolómica
16.
BMC Med ; 21(1): 6, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36600276

RESUMEN

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Farmacovigilancia , Inmunoterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Estudios Retrospectivos
17.
BMC Cancer ; 23(1): 1013, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37864137

RESUMEN

BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.


Asunto(s)
Adenocarcinoma , Neoplasias del Recto , Humanos , Estadificación de Neoplasias , Reparación de la Incompatibilidad de ADN , Estudios Retrospectivos , Pronóstico , Neoplasias del Recto/genética , Neoplasias del Recto/cirugía , Adenocarcinoma/genética , Adenocarcinoma/cirugía
18.
FASEB J ; 36(3): e22210, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35167144

RESUMEN

Precise regulation of chromosome separation through spindle assembly checkpoint (SAC) during oocyte meiosis is critical for mammalian reproduction. The kinetochore plays an important role in the regulation of SAC through sensing microtubule tension imbalance or missing microtubule connections. Here, we report that kinetochore scaffold 1 (KNL1, also known as CASC5), an outer kinetochore protein, plays a critical role in the SAC function of mouse oocytes. KNL1 localized at kinetochores from GVBD to the MII stage, and microinjection of KNL1-siRNA caused accelerated metaphase-anaphase transition and premature first meiosis completion, producing aneuploid eggs. The SAC was prematurely silenced in the presence of unstable kinetochore-microtubule attachments and misaligned chromosomes in KNL1-depleted oocytes. Additionally, KNL1 and MPS1 had a synergistic effect on the activation and maintenance of SAC. Taken together, our results suggest that KNL1, as a kinetochore platform protein, stabilizes SAC to ensure timely anaphase entry and accurate chromosome segregation during oocyte meiotic maturation.


Asunto(s)
Puntos de Control de la Fase M del Ciclo Celular , Meiosis , Proteínas Asociadas a Microtúbulos/metabolismo , Oocitos/metabolismo , Oogénesis , Animales , Células Cultivadas , Femenino , Ratones , Ratones Endogámicos ICR , Proteínas Asociadas a Microtúbulos/genética , Oocitos/citología
19.
Langmuir ; 39(30): 10660-10669, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37466176

RESUMEN

Self-assembly is an important bottom-up fabrication approach based on accurate manipulation of solid-air-liquid interfaces to construct microscale structures using nanoscale materials. This approach plays a substantial role in the fabrication of microsensors, nanosensors, and actuators. Improving the controllability of self-assembly to realize large-scale regular micro/nano patterns is crucial for this approach's further development and wider applications. Herein, we propose a novel strategy for patterning nanoparticle arrays on soft substrates. This strategy is based on a unique process of liquid film rupture self-assembly that is convenient, precise, and cost-efficient for mass manufacturing. This approach involves two key steps. First, suspended liquid films comprising monolayer polystyrene (PS) spheres are realized via liquid-air interface self-assembly over prepatterned microstructures. Second, these suspended liquid films are ruptured in a controlled manner to induce the self-assembly of internal PS spheres around the morphological edges of the underlying microstructures. This nanoparticle array patterning method is comprehensively investigated in terms of the effect of the PS sphere size, morphological effect of the microstructured substrate, key factors influencing liquid film-rupture self-assembly, and optical transmittance of the fabricated samples. A maximum rupture rate of 95.4% was achieved with an optimized geometric and dimensional design. Compared with other nanoparticle-based self-assembly methods used to form patterned arrays, the proposed approach reduces the waste of nanoparticles substantially because all nanoparticles self-assemble around the prepatterned microstructures. More nanoparticles assemble to form prepatterned arrays, which could strengthen the nanoparticle array network without affecting the initial features of prepatterned microstructures.

20.
Langmuir ; 39(49): 17853-17861, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38031448

RESUMEN

Titanium and its alloys are protected by a compact and stable passive film, which confers resistance to corrosion by the primary halogen chloride (Cl-) while being less effective against fluoride (F-). Although researchers have recognized different macroscopic corrosion effects of these halide ions on titanium, the underlying mechanisms remain largely unexplored. In this work, the bonding of Cl-/F- with stable passive films was studied in neutral and acidic (pH = 2.3) conditions. The synergistic effect between the interfacial hydrogen bond (HB) structure and halogens on titanium corrosion was first revealed using first-principles calculation and Raman spectroscopy. F- forms more stable halogen-Ti bonds than Cl-, resulting in titanium degradation. The proton combined with F- exhibits a specific synergistic effect, causing corrosion of the passive film. The water hydrogen bond transformation index (HBTI) at the titanium/aqueous interface was 1.88 in an acidic solution containing F-, significantly higher than that in neutral/acid solutions containing Cl- (1.80/1.81) and a neutral solution containing F- (1.81). This work clarifies the structure-activity relationship between HBTI and the destruction of titanium passive films. We propose that the microstructure of the interfacial HB is an undeniable factor in the corrosion of titanium.

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