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In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.
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Células-Tronco Neurais , Colículos Superiores , Animais , Genes BRCA1 , Neurônios , Proteínas Proto-Oncogênicas c-ets , Xenopus laevis/genética , Proteínas Elk-1 do Domínio ets , Proteína BRCA1RESUMO
OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.
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Synthetic biology aims at designing new biological functions from first principles. These new designs allow to expand the natural solution space and overcome the limitations of naturally evolved systems. One example is synthetic CO2-fixation pathways that promise to provide more efficient ways for the capture and conversion of CO2 than natural pathways, such as the Calvin Benson Bassham (CBB) cycle of photosynthesis. In this review, we provide a practical guideline for the design and realization of such new-to-nature CO2-fixation pathways. We introduce the concept of "synthetic CO2-fixation", and give a general overview over the enzymology and topology of synthetic pathways, before we derive general principles for their design from their eight naturally evolved analogs. We provide a comprehensive summary of synthetic carbon-assimilation pathways and derive a step-by-step, practical guide from the theoretical design to their practical implementation, before ending with an outlook on new developments in the field.
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Dióxido de Carbono , Fotossíntese , Dióxido de Carbono/metabolismo , Carbono/metabolismo , Ciclo do CarbonoRESUMO
OBJECTIVE: The objective was to present our experience on managing mycotic infrarenal abdominal aortic aneurysm (MIAAA) through a retrospective cohort study. METHODS: Data of patients with MIAAA managed in our center from July 2016 to October 2022 were retrospectively analyzed. The diagnosis of MIAAA was made based on: (1) preoperative clinical signs of infection; (2) elevated serologic infection parameters; (3) para-aneurysmal infection features on enhanced computed tomography; and (4) positive blood or tissue cultures. All the patients received standard antibiotic therapy. Surgical management including endovascular aneurysm repair (EVAR), initial EVAR followed by open re-operation, and initial open surgical repair (OSR) were conducted according to disease seriosity, physical condition, and patient's will. Infection index and clinical outcome were evaluated during the follow-up time. RESULTS: A total of 23 patients (21 men; averaged=66.3 years, range=49-79 years) were included, with a mean follow-up time of 19.9 months (range=1-75 months). Bacteria culture from blood or tissue specimen was positive in 15 patients (Salmonella, n=8; Escherichia coli, n=3; methicillin-sensitive Staphylococcus aureus [MSSA], n=1; Klebsiella pneumoniae, n=1; Staphylococcus epidermidis, n=1; Mycobacterium tuberculosis, n=1). Seven patients received OSR as the initial surgical intervention, whereas 14 patients chose EVAR instead. The 2 conservatively managed patients (refused surgery) died within 30 days. The 7 patients who received initial OSR survived till now. Among the 14 patients who underwent initial EVAR, infection deteriorated without exception (14/14, 100%). Three of these patients refused re-operation and died within 6 months. Eleven patients received secondary surgical intervention (10 cases of aneurysm and endograft resection, thorough debridement, subclavian to bi-femoral artery bypass, or in situ aorta reconstruction; 1 case of laparoscopic debridement) and 7 survived the follow-up time. The overall mortality rate was 39.1% (9/23). The mortality rates differed greatly following different intervention methods (merely antibiotic management, 100%; initial open operation, 0%; initial EVAR without secondary operation, 100%; initial EVAR plus secondary operation, 36.4%). CONCLUSIONS: Open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely EVAR is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary OSR. CLINICAL IMPACT: The management of mycotic or primary-infected aortic aneurysm is challenging; treatment remains controversial. Our center has reviewed our experience over the past 6 years and found that open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely endovascular aneurysm repair (EVAR) is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary open surgical repair.
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KEY MESSAGE: Single-cell transcriptomic techniques have emerged as powerful tools in plant biology, offering high-resolution insights into gene expression at the individual cell level. This review highlights the rapid expansion of single-cell technologies in plants, their potential in understanding plant development, and their role in advancing plant biotechnology research. Single-cell techniques have emerged as powerful tools to enhance our understanding of biological systems, providing high-resolution transcriptomic analysis at the single-cell level. In plant biology, the adoption of single-cell transcriptomics has seen rapid expansion of available technologies and applications. This review article focuses on the latest advancements in the field of single-cell transcriptomic in plants and discusses the potential role of these approaches in plant development and expediting plant biotechnology research in the near future. Furthermore, inherent challenges and limitations of single-cell technology are critically examined to overcome them and enhance our knowledge and understanding.
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Biotecnologia , Transcriptoma , Transcriptoma/genética , Perfilação da Expressão Gênica , Desenvolvimento VegetalRESUMO
Molecular sieving is an ideal separation mechanism, but controlling pore size, restricting framework flexibility, and avoiding strong adsorption are all very challenging. Here, we report a flexible adsorbent showing molecular sieving at ambient temperature and high pressure, even under high humidity. While typical guest-induced transformations are observed, a high transition pressure of 16.6â atm is observed for C2H4 at 298â K because of very weak C2H4 adsorption (~16â kJ mol-1). Also, C2H6 is completely excluded below the pore-opening pressure of 7.7â atm, giving single-component selectivity of ca. 300. Quantitative high-pressure column breakthrough experiments using 1 : 1â C2H4/C2H6 mixtures at 10â atm as input confirm molecular sieving with C2H4 adsorption of 0.73â mmol g-1 or 32â cm3(STP) cm-3 and negligible C2H6 adsorption of 0.001(2) mmol g-1, and the adsorbent can be completely regenerated by inert gas purging. Furthermore, it is highly hydrophobic with negligible water adsorption, and the C2H4/C2H6 separation performance is unaffected at high humidity.
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This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.
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Mutação , Fatores de Transcrição NFI , Gêmeos Monozigóticos , Humanos , Fatores de Transcrição NFI/genética , Gêmeos Monozigóticos/genética , Anormalidades Múltiplas/genética , Masculino , Feminino , Anormalidades Craniofaciais/genética , Pré-Escolar , Doenças do Desenvolvimento Ósseo , Displasia Septo-ÓpticaRESUMO
A boy, aged 7 months, presented with severe global developmental delay (GDD), refractory epilepsy, hypotonia, nystagmus, ocular hypertelorism, a broad nasal bridge, everted upper lip, a high palatal arch, and cryptorchidism. Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K) in the EEF1A2 gene, and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation. This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy, genetic testing for EEF1A2 gene mutations should be considered. This is particularly important for those exhibiting hypotonia, nonverbal communication, and craniofacial deformities, to facilitate a confirmed diagnosis.
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Deficiências do Desenvolvimento , Fator 1 de Elongação de Peptídeos , Humanos , Masculino , Lactente , Deficiências do Desenvolvimento/genética , Fator 1 de Elongação de Peptídeos/genética , Epilepsia/genética , Mutação , Mutação de Sentido IncorretoRESUMO
Background: Rice starch has high digestibility due to its large carbohydrate content. Synergistic modification of hot-melt extrusion (HME) and additives such as flavonoids, hydrocolloids, proteins, lipids, and other additives has the tendency to retard the rate of starch hydrolysis. Hence, the current investigation aimed to study the combined effect of the HME-assisted addition of nobiletin (NOB, 0, 2, 4, and 6%) on the multi-scale structures, interactions, thermal, and digestibility characteristics of rice starch. Methods: The study employed density functional theory calculations and an infrared second derivative of an Fourier-transform infrared (FTIR) spectrometer to analyze the interactions between NOB and starch. The physicochemical properties of the starch extrudates were characterized by FTIR, 13C nuclear magnetic resonance, X-ray diffraction, and differential scanning calorimetry, while the digestibility was evaluated using an in vitro digestion model. Results: HME was found to disrupt the crystalline structure, helix structure, short-ordered structure, and thermal properties of starch. The interaction between NOB and starch involved hydrophobic interactions and hydrogen bonds, effectively preventing the molecular chains of starch from interacting with each other and disrupting their double helix structure. The addition of NOB led to the formation of a highly single-helical V-type crystalline structure, along with the formation of ordered structural domains. Consequently, the combined treatment significantly enhanced the ordered structure and thermal stability of starch, thus effectively leading to an increase in resistant starch and slowly digestion starch. Discussion: The study underscores that synergistic modification of HME and NOB holds promise for enhancing both the nutritional value and functional properties of rice starch. These findings offer valuable insights for developing high-quality rice starch products with broader applications.
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Gastrochilus sinensis is a beautiful epiphytic orchid with high ornamental value. In this study, the first complete chloroplast genome sequence of G. sinensis was determined using next-generation sequencing (NGS). The de novo assembled chloroplast genome was 148,020 bp in length, including a pair of inverted repeat regions (IRs; 25,987 bp), a small single-copy region (SSC; 11,045 bp), and a large single-copy region (LSC; 85,001 bp). The chloroplast genome encodes 109 unique genes, including 75 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. The total GC content of the chloroplast genome was 36.8%. The phylogenetic analysis showed a close relationship between G. sinensis and G. formosanus species. The complete chloroplast genome provides fundamental information for genetic diversity and phylogenetic relationships in Gastrochilus.
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BACKGROUND: A comprehensive understanding of the extrahepatic bile duct anatomy is vital to guide surgical procedures and perform endoscopic retrograde cholangiography. Anatomical irregularities within the extrahepatic bile duct may increase susceptibility to bile duct stones. AIM: To investigate the anatomical risk factors associated with extrahepatic bile ducts in patients diagnosed with choledocholithiasis, with a specific focus on preventing stone recurrence after surgical intervention and endoscopic lithotomy. METHODS: We retrospectively analyzed the medical records of 124 patients without choledocholithiasis and 108 with confirmed choledocholithiasis who underwent magnetic resonance cholangiopancreatography examinations at our center between January 2022 and October 2022. Logistic regression analyses were conducted to identify the anatomical risk factors influencing the incidence of common bile duct stones. RESULTS: Multivariate logistic regression analysis revealed that several factors independently contributed to choledocholithiasis risk. Significant independent risk factors for choledocholithiasis were diameter of the common hepatic [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.07-1.92, adjusted P value = 0.016] and common bile (aOR = 1.68, 95%CI: 1.27-2.23, adjusted P value < 0.001) ducts, length of the common hepatic duct (aOR = 0.92, 95%CI: 0.84-0.99, adjusted P value = 0.034), and angle of the common bile duct (aOR = 0.92, 95%CI: 0.89-0.95, adjusted P value < 0.001). CONCLUSION: The anatomical features of the extrahepatic bile duct were directly associated with choledocholithiasis risk. Key risk factors include an enlarged diameter of the common hepatic and bile ducts, a shorter length of the common hepatic duct, and a reduced angle of the common bile duct.
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BACKGROUND AND OBJECTIVE: Stroke has become a major disease threatening the health of people around the world. It has the characteristics of high incidence, high fatality, and a high recurrence rate. At this stage, problems such as poor recognition accuracy of stroke screening based on electronic medical records and insufficient recognition of stroke risk levels exist. These problems occur because of the systematic errors of medical equipment and the characteristics of the collectors during the process of electronic medical record collection. Errors can also occur due to misreporting or underreporting by the collection personnel and the strong subjectivity of the evaluation indicators. METHODS: This paper proposes an isolation forest-voting fusion-multioutput algorithm model. First, the screening data are collected for numerical processing and normalization. The composite feature score index of this paper is used to analyze the importance of risk factors, and then, the isolation forest is used. The algorithm detects abnormal samples, uses the voting fusion algorithm proposed in this article to perform decision fusion prediction classification, and outputs multidimensional (risk factor importance score, abnormal sample label, risk level classification, and stroke prediction) results that can be used as auxiliary decision information by doctors and medical staff. RESULTS: The isolation forest-voting fusion-multioutput algorithm proposed in this article has five categories (zero risk, low risk, high risk, ischemic stroke (TIA), and hemorrhagic stroke (HE)). The average accuracy rate of stroke prediction reached 79.59 %. CONCLUSIONS: The isolation forest-voting fusion-multioutput algorithm model proposed in this paper can not only accurately identify the various categories of stroke risk levels and stroke prediction but can also output multidimensional auxiliary decision-making information to help medical staff make decisions, thereby greatly improving the screening efficiency.
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Algoritmos , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Medição de Risco/métodos , Fatores de Risco , Registros Eletrônicos de Saúde , VotaçãoRESUMO
Full myco-heterotrophic orchid Gastrodia elata Bl. is widely distributed in Northeast Asia, and previous research has not fully investigated the symbiotic fungal community of its early immature tubers. This study utilized Illumina sequencing to compare symbiotic fungal communities in natural G. elata immature tubers and their habitats. LEfSe (Linear Discriminant Analysis Effect Size) was used to screen for Biomarkers that could explain variations among different fungal communities, and correlation analyses were performed among Biomarkers and other common orchid mycorrhizal fungi. Our results illustrate that the symbiotic fungal communities of immature G. elata tubers cannot be simply interpreted as subsets of the environmental fungal communities because some key members cannot be traced back to the environment. The early growth of G. elata was related to a small group of fungi, such as Sebacina, Thelephora, and Inocybe, which were also common mycorrhizal fungi from other orchids. In addition, Mycena, Auricularia, and Cryptococcus were unique fungal partners of G. elata, and many new species have yet to be discovered. Possible symbiotic Mycena should be M. plumipes and its sibling species in this case. Our results provide insight into the symbiotic partner switch and trophic pattern change during the development and maturation of G. elata.
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It remains to be determined whether there is a geographical distribution pattern and phylogenetic signals for the Mycena strains with seed germination of the orchid plant Gastrodia elata. This study analyzed the community composition and phylogenetics of 72 Mycena strains associated with G. elata varieties (G. elata. f. glauca and G. elata. f. viridis) using multiple gene fragments (ITS+nLSU+SSU). We found that (1) these diverse Mycena phylogenetically belong to the Basidiospore amyloid group. (2) There is a phylogenetic signal of Mycena for germination of G. elata. Those strains phylogenetically close to M. abramsii, M. polygramma, and an unclassified Mycena had significantly higher germination rates than those to M. citrinomarginata. (3) The Mycena distribution depends on geographic site and G. elata variety. Both unclassified Mycena group 1 and the M. abramsii group were dominant for the two varieties of G. elata; in contrast, the M. citrinomarginata group was dominant in G. elata f. glauca but absent in G. elata f. viridis. Our results indicate that the community composition of numerous Mycena resources in the Zhaotong area varies by geographical location and G. elata variety. Importantly, our results also indicate that Mycena's phylogenetic status is correlated with its germination rate.
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Gastrodia , Germinação , Filogenia , Gastrodia/microbiologia , Gastrodia/genética , DNA Fúngico/genética , Sementes/microbiologia , Sementes/crescimento & desenvolvimento , Basidiomycota/genética , Basidiomycota/classificação , Basidiomycota/fisiologiaRESUMO
INTRODUCTION: This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. METHODS: A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. RESULTS: On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0 < density ≤ 0.093), G2 (0.093 < density ≤ 0.245), and G3 (0.245 < density ≤ 0.712). Fundus photographs depicted a progressive enlargement of atrophic lesions, evolving from punctate-shaped to patchy with indistinct boundaries. DCA atrophy lesions exhibited a gradual shift in color from brown-yellow to yellow-white, originating from the temporal side of the optic disc and extending towards the macula, with severe cases exhibiting widespread distribution throughout the posterior pole. Patients with DCA were significantly older [34.00 (27.00, 48.00) vs 29.00 (26.00, 34.00) years], possessed a longer axial length (28.85 ± 1.57 vs 27.11 ± 1.01 mm), and exhibited a more myopic spherical equivalent [- 13.00 (- 16.00, - 10.50) vs - 9.09 ± 2.41 D] compared to those without DCA (G0) (all P < 0.001). In eyes with DCA, a trend emerged as grades increased from G1 to G3, showing associations with older age, longer axial length, deeper myopic spherical equivalent, larger area of parapapillary atrophy, and increased fundus tessellated density (all P < 0.001). CONCLUSIONS: The novel grading system for DCA, based on assessments of area and density, serves as a reliable measure for evaluating the severity of this condition, making it suitable for widespread application in the screening of pathologic myopia.
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AIM: To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. METHODS: Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. RESULTS: In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: ß=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: ß=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: ß=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: ß=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. CONCLUSION: The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.
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Formaldehyde is a key metabolite in natural and synthetic one-carbon metabolism. To facilitate the engineering of formaldehyde-producing enzymes, the development of sensitive, user-friendly, and cost-effective detection methods is required. In this study, we engineered Escherichia coli to serve as a cellular biosensor capable of detecting a broad range of formaldehyde concentrations. Using both natural and promiscuous formaldehyde assimilation enzymes, we designed three distinct E. coli growth biosensor strains that depend on formaldehyde for cell growth. These strains were engineered to be auxotrophic for one or several essential metabolites that could be produced through formaldehyde assimilation. The respective assimilating enzyme was expressed from the genome to compensate the auxotrophy in the presence of formaldehyde. We first predicted the formaldehyde dependency of the biosensors by flux balance analysis and then analysed it experimentally. Subsequent to strain engineering, we enhanced the formaldehyde sensitivity of two biosensors either through adaptive laboratory evolution or modifications at metabolic branch points. The final set of biosensors demonstrated the ability to detect formaldehyde concentrations ranging approximately from 30 µM to 13 mM. We demonstrated the application of the biosensors by assaying the in vivo activity of different methanol dehydrogenases in the most sensitive strain. The fully genomic nature of the biosensors allows them to be deployed as "plug-and-play" devices for high-throughput screenings of extensive enzyme libraries. The formaldehyde growth biosensors developed in this study hold significant promise for advancing the field of enzyme engineering, thereby supporting the establishment of a sustainable one-carbon bioeconomy.
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Técnicas Biossensoriais , Escherichia coli , Formaldeído , Engenharia Metabólica , Formaldeído/metabolismo , Técnicas Biossensoriais/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Engenharia Metabólica/métodos , Oxirredutases do Álcool/metabolismo , Oxirredutases do Álcool/genética , Biotecnologia/métodosRESUMO
OBJECTIVE: To explore the clinical characteristics, molecular characteristics, treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) with a therapeutic target. METHODS: A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021. The data of age, gender, white blood cell (WBC) count at initial diagnosis, genetic characteristics, molecular biological changes, chemotherapy regimen, different targeted drugs were given, and minimal residual disease (MRD) on day 19, MRD on day 46, whether hematopoietic stem cell transplantation (HSCT) were retrospective analyed, and the clinical characteristics and treatment effect were summarized. Survival analysis was performed by Kaplan-Meier method. RESULTS: The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients, 10 patients were treated with targeted drugs during treatment, and 3 patients were bridged with HSCT, 1 patient died and 2 patients survived. Among the 24 patients who did not receive HSCT, 1 patient developed relapse, and achieved complete remission (CR) after treatment with chimeric antigen receptors T cells (CAR-T). The 3-year overall survival, 3-year relapse-free survival and 3-year event-free survival rate of 27 patients were (95.5±4.4)%, (95.0±4.9)% and (90.7±6.3)% respectively. CONCLUSION: Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children, combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor, and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Criança , Humanos , Cromossomo Filadélfia , Estudos Retrospectivos , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Neoplasia Residual , Resposta Patológica Completa , RecidivaRESUMO
BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. METHODS: The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. ß-catenin nuclear localization was examined by western blotting and confocal microscopy. RESULTS: NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted ß-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce ß-catenin nuclear translocation under OS conditions in PDLSCs. CONCLUSIONS: NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.