Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 128
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Cell Mol Med ; 28(8): e18292, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38652116

RESUMEN

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.


Asunto(s)
Salmonella enterica , Serogrupo , Espectrometría Raman , Máquina de Vectores de Soporte , Espectrometría Raman/métodos , Salmonella enterica/aislamiento & purificación , Humanos , Algoritmos
2.
Lab Invest ; 104(2): 100310, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38135155

RESUMEN

Diagnostic methods for Helicobacter pylori infection include, but are not limited to, urea breath test, serum antibody test, fecal antigen test, and rapid urease test. However, these methods suffer drawbacks such as low accuracy, high false-positive rate, complex operations, invasiveness, etc. Therefore, there is a need to develop simple, rapid, and noninvasive detection methods for H. pylori diagnosis. In this study, we propose a novel technique for accurately detecting H. pylori infection through machine learning analysis of surface-enhanced Raman scattering (SERS) spectra of gastric fluid samples that were noninvasively collected from human stomachs via the string test. One hundred participants were recruited to collect gastric fluid samples noninvasively. Therefore, 12,000 SERS spectra (n = 120 spectra/participant) were generated for building machine learning models evaluated by standard metrics in model performance assessment. According to the results, the Light Gradient Boosting Machine algorithm exhibited the best prediction capacity and time efficiency (accuracy = 99.54% and time = 2.61 seconds). Moreover, the Light Gradient Boosting Machine model was blindly tested on 2,000 SERS spectra collected from 100 participants with unknown H. pylori infection status, achieving a prediction accuracy of 82.15% compared with qPCR results. This novel technique is simple and rapid in diagnosing H. pylori infection, potentially complementing current H. pylori diagnostic methods.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/diagnóstico , Espectrometría Raman , Estómago , Ureasa/análisis , Sensibilidad y Especificidad
3.
Crit Rev Microbiol ; : 1-30, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910506

RESUMEN

Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.

4.
J Ultrasound Med ; 43(4): 741-749, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38158852

RESUMEN

OBJECTIVES: To investigate the influence of microbubble perfusion mode on catheter-directed thrombolysis (CDT), we evaluated the effect of two different types of microbubble perfusion modes (continuous injection versus bolus injection) on the thrombolytic efficacy of CDT in vitro and further assessed the effect of continuous microbubble injection on CDT in vivo. METHODS: In an in vitro experimental setup, 50 fresh bovine whole blood clots were randomized into five groups: ultrasound and continuous microbubble injection-enhanced CDT (US + cMB + CDT), ultrasound and bolus microbubble injection-enhanced CDT (US + bMB + CDT), US + CDT, US + cMB, and CDT. In a porcine femoral vein thrombosis model, 16 completely obstructive thrombi were randomly assigned to the CDT group and the US + cMB + CDT group, respectively. Thrombolysis rate, vascular recanalization rate, hematoxylin-eosin, and immunofluorescence staining were used to evaluate the thrombolytic effect in vitro and in vivo. RESULTS: In vitro, US + cMB + CDT group resulted in a significantly higher thrombolysis rate compared with the other four groups (P < .05). Meanwhile, this group also demonstrated a looser clot structure and more disrupted fibrin structures. In vivo, US + cMB + CDT contributed to a significantly higher vascular recanalization rate compared with CDT (87.50% versus 25.00%, P < .05). CONCLUSIONS: US + cMB + CDT was more effective than US + bMB + CDT in thrombolysis, and ultrasound combined with continuous microbubble injection could enhance the thrombolytic efficacy of CDT.


Asunto(s)
Terapia Trombolítica , Trombosis , Animales , Bovinos , Porcinos , Terapia Trombolítica/métodos , Microburbujas , Fibrinolíticos , Ultrasonografía , Catéteres , Trombosis/terapia , Resultado del Tratamiento
5.
J Ultrasound Med ; 43(7): 1245-1250, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38477076

RESUMEN

OBJECTIVES: Ultrasound (US) imaging has been observed to underestimate tumor size in clinical practice. This study aims to compare the size measurements of breast cancer and benign tumors using two-dimensional ultrasound (2DUS) and contrast-enhanced ultrasound (CEUS). METHODS: The study included 42 clinically confirmed breast cancer and 47 benign breast tumors. Two experienced physicians independently measured the maximal longitudinal and transverse diameters of the masses in 2DUS and CEUS. All analyses were performed in R (4.2.2) and GraphPad Prism 6. RESULTS: The maximal longitudinal and transverse diameters of breast cancer measured by CEUS were 26.61 ± 0.21% and 26.24 ± 0.19% larger compared with 2DUS, and benign breast tumors had an 11.74 ± 0.21% and 11.06 ± 0.14% increase in size compared with 2DUS. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the difference between 2DUS and CEUS was 0.870 for longitudinal diameters (95% CI: 0.795-0.945, sensitivity 0.842, specificity 0.783, threshold value 0.215), and 0.863 for transverse diameters (95% CI: 0.785-0.942, sensitivity 0.667, specificity 0.936, threshold value 0.203). CONCLUSIONS: The size measurements of both breast cancer and benign tumors were larger in CEUS compared with 2DUS, with CEUS measurements of breast cancer being more pronounced than those of benign breast tumors. These findings suggest that CEUS may provide a more precise assessment of tumor size, which is crucial for determining optimal treatment strategies and improving patient outcomes in breast cancer management.


Asunto(s)
Neoplasias de la Mama , Mama , Medios de Contraste , Aumento de la Imagen , Sensibilidad y Especificidad , Ultrasonografía Mamaria , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Aumento de la Imagen/métodos , Adulto , Reproducibilidad de los Resultados , Mama/diagnóstico por imagen , Mama/patología , Anciano , Diagnóstico Diferencial , Carga Tumoral
6.
J Ultrasound Med ; 43(2): 253-263, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37853950

RESUMEN

OBJECTIVES: To investigate the appropriate combination of pulse length (PL) and pulse repetition frequency (PRF) when performing ultrasound stimulated microbubble (USMB) to enhance doxorubicin (DOX) delivery to tumors. METHODS: A total of 48 tumor-bearing mice were divided into four groups, namely groups A-D. The mice in groups B-D were treated with chemotherapy and USMB treatment with different combinations of PL and PRF, and group A was control. Contrast-enhanced ultrasound imaging was conducted to analyze tumor blood perfusion. Fluorescence microscopy and high-performance liquid chromatography were used to qualitatively and quantitatively analyse DOX release. The structural changes of tumors were observed under light microscope and transmission electron microscope. Furthermore, another 24 tumor-bearing mice were treated with sonochemotherapy and some related inflammatory factors were measured to explore the underlying mechanism. RESULTS: With PL of three cycles and PRF of 2 kHz, the tumor perfusion area ratio increased by 26.67%, and the DOX concentration was 4.69 times higher than the control (P < .001). With PL of 34.5 cycles and PRF of 200 Hz, the tumor perfusion area ratio decreased by 12.7% and DOX did not exhibit increased extravasation compared with the control. Microvascular rupture and hemorrhage were observed after long PL and low PRF treatment. While vasodilation and higher levels of some vasodilator inflammatory factors were found after treatment with short PL and high PRF. CONCLUSIONS: USMB treatment using short PL and high PRF could enhance tumor blood perfusion and increase DOX delivery, whereas long PL and low PRF could not serve the same purpose.


Asunto(s)
Doxorrubicina , Neoplasias , Ratones , Animales , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Ultrasonografía/métodos , Perfusión , Microburbujas
7.
Molecules ; 29(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38792150

RESUMEN

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.


Asunto(s)
Factor B del Complemento , Estructura Molecular , Factor B del Complemento/antagonistas & inhibidores
8.
World J Microbiol Biotechnol ; 40(5): 146, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38538920

RESUMEN

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Acinetobacter , Humanos , Espectrometría Raman , Infecciones por Acinetobacter/microbiología
9.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1397-1405, 2024 Mar.
Artículo en Zh | MEDLINE | ID: mdl-38621988

RESUMEN

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional de Asia Oriental , Complejos Prematuros Ventriculares , Humanos , Complejos Prematuros Ventriculares/tratamiento farmacológico , Medicamentos sin Prescripción/uso terapéutico , Reproducibilidad de los Resultados , Medicamentos Herbarios Chinos/uso terapéutico , Cápsulas
10.
Angew Chem Int Ed Engl ; : e202406167, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818573

RESUMEN

The planar triple-layer hole transport layer (HTL)-free carbon-based perovskite solar cells (C-PSCs) have outstanding advantages of low cost and high stability, but are limited by low efficiency. The formation of a 3D/2D heterojunction has been widely proven to enhance device performance. However, the 2D perovskite possesses multiple critical properties associated with 3D perovskite, including defect passivation, energy level, and charge transport properties, all of which can impact device performance. It is challenging to find a powerful means to achieve comprehensive regulation and trade-off of these key properties. Herein, we propose a chain-length engineering of alkylammonium spacer cations to achieve this goal. The results show that the 2D perovskite formed by short-chain alkylammonium cations primarily acts to passivate defects. With the increase in cation chain length, the 2D perovskite achieves a more matched energy level with 3D perovskite, enhancing the built-in electric field and promoting charge separation. However, the further increase in chain length impedes the charge transport due to the insulativity of organic cations. Comprehensively, the 2D perovskite formed by tetradecylammonium cations achieves the optimal balance of defect passivation, interface charge separation, and charge transport. The planar HTL-free C-PSCs exhibit a new record efficiency of 20.40% (certified 20.1%).

11.
Connect Tissue Res ; 64(3): 219-228, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36594156

RESUMEN

PURPOSE: BMP-8a is a member of bone morphogenetic proteins (BMPs) and plays a regulatory role in human growth and development as a transcription regulator. This review aims to summarize the current research on the impact and mechanism of BMP-8a in female and male reproduction, formation and eruption of teeth, bone and cartilage development, tissue differentiation, disease occurrence, progression and prognosis. METHODS: The phrases "BMP-8a," "BMPs," "regulator," "mechanism," "osteoblast," "cartilage," "cancer," "disease," and "inflammation" were searched in the PubMed database. The abstracts were evaluated, and a series of original publications and reviews were examined. RESULTS: According to the search, BMP-8a affects the development of the uterus by inhibiting luteinization and plays an important role in late spermatogenesis. It is highly expressed in osteogenesis and differentially expressed in chondrogenesis. Furthermore, BMP-8a has a significant impact on the occurrence, development and prognosis of various diseases. CONCLUSIONS: BMP-8a regulates important factors and pathways, such as SMAD2/3 and SMAD1/5/8, to promote or inhibit the developmental processes of human reproductive organs. BMP-8a is also a member of the BMP family of proteins that regulates chondrogenesis and osteogenesis. In addition to its osteoinductive capabilities, BMP-8a is involved in the progression of diverse cancers.


Asunto(s)
Proteínas Morfogenéticas Óseas , Transducción de Señal , Femenino , Humanos , Masculino , Biología , Proteínas Morfogenéticas Óseas/metabolismo , Cartílago/metabolismo , Diferenciación Celular , Osteogénesis
12.
Appl Microbiol Biotechnol ; 107(18): 5701-5714, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37480372

RESUMEN

Staurosporine is the most well-known member of the indolocarbazole alkaloid family; it can induce apoptosis of many types of cells as a strong protein kinase inhibitor, and is used as an important lead compound for the synthesis of the antitumor drugs. However, the low fermentation level of the native producer remains the bottleneck of staurosporine production. Herein, integration of multi-copy biosynthetic gene cluster (BGC) in well characterized heterologous host and optimization of the fermentation process were performed to enable high-level production of staurosporine. First, the 22.5 kb staurosporine BGC was captured by CRISPR/Cas9-mediated TAR (transformation-associated recombination) from the native producer (145 mg/L), and then introduced into three heterologous hosts Streptomyces avermitilis (ATCC 31267), Streptomyces lividans TK24 and Streptomyces albus J1074 to evaluate the staurosporine production capacity. The highest yield was achieved in S. albus J1074 (750 mg/L), which was used for further production improvement. Next, we integrated two additional staurosporine BGCs into the chromosome of strain S-STA via two different attB sites (vwb and TG1), leading to a double increase in the production of staurosporine. And finally, optimization of fermentation process by controlling the pH and glucose feeding could improve the yield of staurosporine to 4568 mg/L, which was approximately 30-fold higher than that of the native producer. This is the highest yield ever reported, paving the way for the industrial production of staurosporine. KEYPOINTS: • Streptomyces albus J1074 was the most suitable heterologous host to express the biosynthetic gene cluster of staurosporine. • Amplification of the biosynthetic gene cluster had obvious effect on improving the production of staurosporine. • The highest yield of staurosporine was achieved to 4568 mg/L by stepwise increase strategy.


Asunto(s)
Inhibidores de Proteínas Quinasas , Streptomyces griseus , Estaurosporina , Fermentación , Apoptosis
13.
Knee Surg Sports Traumatol Arthrosc ; 31(6): 2289-2298, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36534149

RESUMEN

PURPOSE: As a simple and invasive treatment, arthroscopic medial meniscal posterior horn resections (MMPHRs) can relieve the obstructive symptoms of medial meniscus posterior root tears (MMPRTs) but with the risk of aggravating biomechanical changes of the joint. The aim of this study was to analyze dynamic simulation of the knee joint after medial meniscus posterior root tear and posterior horn resection. METHODS: This study established static and dynamic models of MMPRTs and MMPHRs on the basis of the intact medial meniscus model (IMM). In the finite element analysis, the three models were subjected to 1000 N axial static load and the human walking gait load defined by the ISO14243-1 standard to evaluate the influence of MMPRTs and MMPHRs on knee joint mechanics during static standing and dynamic walking. RESULTS: In the static state, the load ratio of the medial and lateral compartments remained nearly constant (2:1), while in the dynamic state, the load ratio varied with the gait cycle. After MMPHRs, at 30% of the gait cycle, compared with the MMPRTs condition, the maximum von Mises stress of the lateral meniscus (LM) and the lateral tibial cartilage (LTC) were increased by 166.0% and 50.0%, respectively, while they changed by less than 5% during static analysis. The maximum von Mises stress of the medial meniscus (MM) decreased by 55.7%, and that of the medial femoral cartilage (MFC) increased by 53.5%. CONCLUSION: After MMPHRs, compared with MMPRTs, there was no significant stress increase in articular cartilage in static analysis, but there was a stress increase and concentration in both medial and lateral compartments in dynamic analysis, which may aggravate joint degeneration. Therefore, in clinical treatments, restoring the natural structure of MMPRTs is first recommended, especially for physically active patients.


Asunto(s)
Traumatismos de la Rodilla , Lesiones de Menisco Tibial , Humanos , Meniscos Tibiales/cirugía , Meniscectomía/efectos adversos , Lesiones de Menisco Tibial/cirugía , Traumatismos de la Rodilla/cirugía , Fenómenos Biomecánicos , Articulación de la Rodilla/cirugía , Marcha
14.
J Sci Food Agric ; 103(11): 5452-5461, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37046375

RESUMEN

BACKGROUND: Lotus roots (Nelumbo nucifera Gaertn.) are rich in nutrients and have ornamental and food value. However, browning has caused huge economic losses and security risks during the storage and harvesting of fresh-cut lotus. This study investigated the role of melatonin in inhibiting lotus browning, and illustrates its molecular mechanism. RESULTS: The application of melatonin effectively retarded the process of lotus browning, enhanced reactive oxygen species (ROS) scavenging enzyme activity, and inhibited the activity of polyphenol oxidase (PPO), and peroxidase (POD). Melatonin reduced flavonoid content, and decreased enzymatic activity in flavonoid biosynthesis. Transcriptome Sequencing (RNA-seq) was used to screen the genes regulated by exogenous melatonin when defending against fresh-cut lotus browning. Gene co-expression analysis (GCN) indicated that the transcription factors MYB5, MYB6, and MYB308, activated by melatonin, were negatively related to the expression of PPO and the genes related to flavonoid and phenylpropanoid biosynthesis. These myeloblastosis viral oncogene homologs (MYBs) were positively related to the expression of genes encoding the enzymes in glutathione metabolism. CONCLUSION: Melatonin retarded lotus browning by transcriptional suppression of key genes associated with flavonoid and phenylpropanoid biosynthesis through the stimulation of MYB5, MYB6, and MYB308. © 2023 Society of Chemical Industry.


Asunto(s)
Melatonina , Melatonina/farmacología , Especies Reactivas de Oxígeno , Peroxidasa/metabolismo , Perfilación de la Expresión Génica , Oncogenes
15.
Microb Cell Fact ; 21(1): 240, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36419063

RESUMEN

BACKGROUND: Acarbose, as an alpha-glucosidase inhibitor, is widely used clinically to treat type II diabetes. In its industrial production, Actinoplanes sp. SE50/110 is used as the production strain. Lack of research on its regulatory mechanisms and unexplored gene targets are major obstacles to rational strain design. Here, transcriptome sequencing was applied to uncover more gene targets and rational genetic engineering was performed to increase acarbose production. RESULTS: In this study, with the help of transcriptome information, a TetR family regulator (TetR1) was identified and confirmed to have a positive effect on the synthesis of acarbose by promoting the expression of acbB and acbD. Some genes with low expression levels in the acarbose biosynthesis gene cluster were overexpressed and this resulted in a significant increase in acarbose yield. In addition, the regulation of metabolic pathways was performed to retain more glucose-1-phosphate for acarbose synthesis by weakening the glycogen synthesis pathway and strengthening the glycogen degradation pathway. Eventually, with a combination of multiple strategies and fed-batch fermentation, the yield of acarbose in the engineered strain increased 58% compared to the parent strain, reaching 8.04 g/L, which is the highest fermentation titer reported. CONCLUSIONS: In our research, acarbose production had been effectively and steadily improved through genetic engineering based on transcriptome analysis and fed-batch culture strategy.


Asunto(s)
Actinoplanes , Diabetes Mellitus Tipo 2 , Humanos , Acarbosa , Fermentación , Ingeniería Genética , Glucógeno
16.
Bioorg Med Chem ; 70: 116921, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35863237

RESUMEN

>90% of genes in the human body undergo alternative splicing (AS) after transcription, which enriches protein species and regulates protein levels. However, there is growing evidence that various genetic isoforms resulting from dysregulated alternative splicing are prevalent in various types of cancers. Dysregulated alternative splicing leads to cancer generation and maintenance of cancer properties such as proliferation differentiation, apoptosis inhibition, invasion metastasis, and angiogenesis. Serine/arginine-rich proteins and SR protein-associated kinases mediate splice site recognition and splice complex assembly during variable splicing. Based on the impact of dysregulated alternative splicing on disease onset and progression, the search for small molecule inhibitors targeting alternative splicing is imminent. In this review, we discuss the structure and specific biological functions of SR proteins and describe the regulation of SR protein function by SR protein related kinases meticulously, which are closely related to the occurrence and development of various types of cancers. On this basis, we summarize the reported small molecule inhibitors targeting SR proteins and SR protein related kinases from the perspective of medicinal chemistry. We mainly categorize small molecule inhibitors from four aspects, including targeting SR proteins, targeting Serine/arginine-rich protein-specific kinases (SRPKs), targeting Cdc2-like kinases (CLKs) and targeting dual-specificity tyrosine-regulated kinases (DYRKs), in terms of structure, inhibition target, specific mechanism of action, biological activity, and applicable diseases. With this review, we are expected to provide a timely summary of recent advances in alternative splicing regulated by kinases and a preliminary introduction to relevant small molecule inhibitors.


Asunto(s)
Empalme Alternativo , Serina , Arginina/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Serina/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo
17.
Environ Res ; 214(Pt 4): 114103, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35987375

RESUMEN

Activated carbon (AC) is negatively charged in aqueous solution, which seriously restricts its application range. Quaternary ammonium salt as a common cationic surfactant was utilized to modify the surface charge distribution of materials. The evolution of the surface charge distribution of AC modified by benzalkonium chloride (BAC), diallyl dimethyl ammonium chloride (DDA) and 3-chloro-2-hydroxypropyl tri-methyl ammonium chloride (CTA) was investigated. Results showed that the surface charge of AC modified by CTA does not change significantly. BAC has a high molecular weight, low surface electrostatic potential and large steric hindrance due to its hydrophobic long-chain alkyl. The diffusion of BAC molecules from solution to AC changed its charge distribution. But these molecules were difficult to combine with AC surface, and most of them were adsorbed into the pores of AC to form aggregates, resulting in a significant reduction in the surface area. BAC modified AC could enhance the adsorption capacity of F- in aqueous solution through electrostatic attraction, but the improvement effect was limited due to the reduction of surface area, and the maximum adsorption capacity was only increased from 1.18 to 3.31 mg/g. DDA has a small molecular weight and high surface electrostatic potential and easily binds to the surface of AC. Some CC bonds in DDA combined with the ionized hydrogen ions derived from phenolic hydroxyl groups in AC to form carbonium-ions. Then, they could react with AC to form ether bonds, causing DDA to be closely bonded with the surface of AC. DDA realizes the targeted regulation of the surface charge distribution of AC, it has little effect on the porous structure of AC. The modified AC still maintained strong adsorption capacity, and the maximum adsorption capacity for F- was 54.98 mg/g. Meanwhile, a large number of zeolites were loaded on the modified AC and formed coating structures.


Asunto(s)
Compuestos de Amonio , Contaminantes Químicos del Agua , Adsorción , Cloruro de Amonio , Carbón Orgánico/química , Sales (Química) , Agua/química , Contaminantes Químicos del Agua/química
18.
Molecules ; 27(14)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35889471

RESUMEN

As the largest group of structurally diverse metabolites, terpenoids are versatile natural compounds that act as metabolism mediators, plant volatiles, and ecological communicators. However, few terpenoid compounds have been identified in plant parts of sacred lotus (Nelumbo nucifera Gaertn.). To elucidate the molecular genetic basis of the terpene biosynthetic pathway, terpenes from different parts of the plant, including seeds (S), young leaves (YL), mature leaves (ML), white flowers (WF), yellow flowers (YF), and red flowers (RF), were identified by LC-MS/MS and the relative contents of the same terpenes in different parts were compared. The results indicate that all plant parts primarily consist of triterpenes, with only minor quantities of sesquiterpenes and diterpenes, and there were differences in the terpene content detected in different plant parts. To illustrate the biosynthesis of various terpenoids, RNA sequencing was performed to profile the transcriptomes of various plant parts, which generated a total of 126.95 GB clean data and assembled into 29,630 unigenes. Among these unigenes, 105 candidate unigenes are involved in the mevalonate (MVA) pathway, methyl-erythritol phosphate (MEP) pathway, terpenoid backbone biosynthesis pathway, and terpenoid synthases pathway. Moreover, the co-expression network between terpene synthase (TPS) and WRKY transcription factors provides new information for the terpene biosynthesis pathway.


Asunto(s)
Nelumbo , Cromatografía Liquida , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Nelumbo/genética , Espectrometría de Masas en Tándem , Terpenos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcriptoma/genética
19.
Inorg Chem ; 60(21): 16803-16809, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34658234

RESUMEN

A novel two-fold interpenetrated metal-organic framework, namely Co-EDDA, was synthesized by hydrothermal reaction of 5,5'-[ethane-1,2-diylbis(oxy)]diisophthalic acid (H4EDDA), Co(NO3)2·6H2O, and 1,4-di(1H-imidazol-1-yl)benzene in water in an alkaline environment and structurally characterized. Co-EDDA could display clear dual-emission signals at 350 and 430 nm, representing the charge transfer emission between metal ions and the ligand and the ligand-based emission, respectively, which represents the ratiometric luminescence response to chromium(III) with high selectivity and sensitivity (limit of detection of 0.54 µM). Comprehensive studies indicate that the detection can be attributed to the interaction between the Cr3+ ions and the O atoms on the ether bond in Co-EDDA.

20.
BMC Geriatr ; 21(1): 731, 2021 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-34952569

RESUMEN

BACKGROUND: Coronary heart disease (CHD), sarcopenia and depression are common disorders that markedly impair quality of life and impose a huge financial burden on society. They are also frequently comorbid, exacerbating condition and worsening prognosis. This study aimed to investigate the additive effects of CHD and sarcopenia on the risk of new onset depressive symptoms in older adults. METHODS: The prospective cohort study comprised 897 Chinese community-dwelling participants who were aged 60 years and older (386 men; mean age 66.9 ± 5.9 years) without depressive symptoms at baseline, recruited from Chadian of Tianjin, China. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) criteria. CHD was identified via medical records or new diagnosed by at least two physicians. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) ≥11. Longitudinal data on new onset depressive symptoms were collected up to 12 months after baseline. RESULTS: We found that 103 (11.5%) of the 897 participants without depressive symptoms at baseline had developed depressive symptoms. Participants were classified into mutually exclusive groups based on sarcopenia status and CHD: normal, CHD alone, sarcopenia alone, and co-occurring groups. A logistic regression showed that the CHD alone [odd ratios (OR) = 1.78, 95% confidence interval (CI) = 1.05-3.02], sarcopenia alone (OR = 2.79, 95% CI = 1.26-6.22), and co-occurring (OR = 7.19, 95% CI = 2.75-18.81) had higher risk of depressive symptoms than the normal group after adjusting for the covariates. CONCLUSIONS: CHD and sarcopenia synergistically increase the risk of new onset depressive symptoms in older adults. Thus, older adults may require early detection, and appropriate interventions should be implemented.


Asunto(s)
Enfermedad Coronaria , Sarcopenia , Anciano , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Depresión/diagnóstico , Depresión/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Sarcopenia/diagnóstico , Sarcopenia/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA