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Developing robust non-platinum electrocatalysts with multifunctional active sites for pH-universal hydrogen evolution reaction (HER) is crucial for scalable hydrogen production through electrochemical water splitting. Here ultra-small ruthenium-nickel alloy nanoparticles steadily anchored on reduced graphene oxide papers (Ru-Ni/rGOPs) as versatile electrocatalytic materials for acidic and alkaline HER are reported. These Ru-Ni alloy nanoparticles serve as pH self-adaptive electroactive species by making use of in situ surface reconstruction, where surface Ni atoms are hydroxylated to produce bifunctional active sites of Ru-Ni(OH)2 for alkaline HER, and selectively etched to form monometallic Ru active sites for acidic HER, respectively. Owing to the presence of Ru-Ni(OH)2 multi-site surface, which not only accelerates water dissociation to generate reactive hydrogen intermediates but also facilitates their recombination into hydrogen molecules, the self-supported Ru90Ni10/rGOP hybrid electrode only takes overpotential of as low as ≈106 mV to deliver current density of 1000 mA cm-2, and maintains exceptional stability for over 1000 h in 1 m KOH. While in 0.5 m H2SO4, the Ru90Ni10/rGOP hybrid electrode exhibits acidic HER catalytic behavior comparable to commercially available Pt/C catalyst due to the formation of monometallic Ru shell. These electrochemical behaviors outperform some of the best Ru-based catalysts and make it attractive alternative to Pt-based catalysts toward highly efficient HER.
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BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Tetraciclina , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Tetraciclina/uso terapéutico , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Bismuto/uso terapéutico , Bismuto/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Adulto , Helicobacter pylori/efectos de los fármacos , Resultado del Tratamiento , China , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Esquema de Medicación , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificación , Anciano , Adulto Joven , Pruebas Respiratorias , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
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Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Esquema de Medicación , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Sulfonamidas , Tetraciclina , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/efectos de los fármacos , Persona de Mediana Edad , Masculino , Femenino , Tetraciclina/administración & dosificación , Tetraciclina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Bismuto/administración & dosificación , Bismuto/uso terapéutico , Bismuto/efectos adversos , Adulto , Claritromicina/administración & dosificación , Amoxicilina/administración & dosificación , Sulfonamidas/administración & dosificación , Pirroles/administración & dosificación , Pirroles/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Pruebas Respiratorias , Resultado del Tratamiento , Anciano , ChinaRESUMEN
OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.
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Accidente Cerebrovascular , Humanos , Masculino , Recién Nacido , Femenino , China/epidemiología , Accidente Cerebrovascular/epidemiología , Pronóstico , Electroencefalografía , Incidencia , Imagen por Resonancia MagnéticaRESUMEN
Lipid accumulation in hepatocytes is the distinctive characteristic of nonalcoholic fatty liver disease. Serine/arginine-rich splicing factor 3 (SRSF3) is highly expressed in the liver and expression decreases in high-fat conditions. However, the role of SRSF3 in hepatic lipid metabolism needs to be clarified. Here, we showed that loss of SRSF3 was associated with lipid accumulation. We determined that SRSF3 regulated lipophagy, the process of selective degradation of lipid droplets by autophagy. Mechanistically, loss of SRSF3 impaired the fusion of the autophagosome and lysosome by promoting the proteasomal degradation of syntaxin 17 (STX17), a key autophagosomal SNARE protein. We found that ubiquitination of STX17 was increased and upregulation of seven in absentia homolog 1 was responsible for the increased posttranslational modification of STX17. Taken together, our data primarily demonstrate that loss of SRSF3 weakens the clearance of fatty acids by impairing lipophagy in the progression of nonalcoholic fatty liver disease, indicating a novel potential therapeutic target for fatty liver disease treatment.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Autofagia/genética , Ácidos Grasos/metabolismo , Hepatocitos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Factores de Empalme de ARN/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Ubiquitinación , Proteínas Qa-SNARE/metabolismoRESUMEN
Mitochondrion-lysosome interactions have garnered significant attention in recent research. Numerous studies have shown that mitochondrion-lysosome interactions, including mitochondrion-lysosome contact (MLC) and mitophagy, are involved in various biological processes and pathological conditions. Single fluorescent probes are termed a pivotal chemical tool in unraveling the intricate spatiotemporal interorganelle interplay in live cells. However, current chemical tools are insufficient to deeply understand mitochondrion-lysosome dynamic interactions and related diseases, Moreover, the rational design of mitochondrion-lysosome dual-targeting fluorescent probes is intractable. Herein, we designed and synthesized a pH-sensitive fluorescent probe called INSA, which could simultaneously light up mitochondria (red emission) and lysosomes (green emission) for their internal pH differences. Employing INSA, we successfully recorded long-term dynamic interactions between lysosomes and mitochondria. More importantly, the increasing mitochondrion-lysosome interactions in ferroptotic cells were also revealed by INSA. Further, we observed pH variations in mitochondria and lysosomes during ferroptosis for the first time. In brief, this work not only introduced a pH-sensitive fluorescent probe INSA for the disclosure of the mitochondrion-lysosome dynamic interplays but also pioneered the visualization of the organellar pH alternation in a specific disease model.
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Colorantes Fluorescentes , Lisosomas , Humanos , Colorantes Fluorescentes/metabolismo , Lisosomas/metabolismo , Mitocondrias , Células HeLa , Concentración de Iones de HidrógenoRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by ectopic lipid accumulation in hepatocytes. To date, no specific drug has been approved for its treatment. Metabotropic glutamate receptor 5 (mGluR5) has been showed expressed in hepatocytes and related to some liver diseases such as alcoholic steatosis. However, the function of mGluR5 in NAFLD is not clear. This work aims to investigate the effect and potential mechanism of mGluR5 in NAFLD. We found that mGluR5 expression was increased in the livers of HFD-fed mice and in palmitate-treated HepG2 cells. Suppression of mGluR5 by the specific antagonist MPEP could ameliorate palmitate-induced lipid accumulation, whereas the mGluR5 agonist CHPG promoted lipid deposition in the cells. Knockdown of mGluR5 by small interfering RNA further demonstrated that inhibition of mGluR5 could reduce lipid accumulation. Furthermore, our results revealed that mGluR5 regulated lipid metabolism by increasing the gene expression of lipogenesis. Inflammatory factors and phosphorylation levels of NF-κB-p65 and JNK were also tested in treated hepatocytes. mGluR5 promoted the inflammatory reaction and JNK phosphorylation. Inhibition of JNK signaling by JNK-IN-8 rescued CHPG-induced lipogenesis and inflammation. This study showed mGluR5 regulated lipid accumulation and inflammation in palmitic acid-treated HepG2 cells via the JNK signaling pathway. mGluR5 might be a potential drug target for NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Ratones , Dieta Alta en Grasa , Células Hep G2 , Hepatocitos/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Palmitatos/farmacología , Receptor del Glutamato Metabotropico 5/metabolismo , Receptor del Glutamato Metabotropico 5/uso terapéuticoRESUMEN
poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Actinas/metabolismo , Línea Celular Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Proyectos Piloto , Furazolidona/efectos adversos , Quimioterapia Combinada , Antibacterianos , Amoxicilina , Metronidazol , Claritromicina/efectos adversos , Resultado del TratamientoRESUMEN
Benzothiazolium and benzoxazolium are common groups for the construction of hemicyanine dyes; however, their isosteric analogue benzoselenazolium have rarely been studied. Here, we report the development of the first benzoselenazolium-based hemicyanine dye for the selective detection of G-quadruplexes. This molecule, SEMA-1, was validated as a red-emitting and activatable fluorescent probe whose fluorescence would only be activated in the presence of G-quadruplexes in buffer solution. Consistent with this, SEMA-1 was found to accumulate in nucleoli and could be used to detect the high abundance of nucleolar rDNA and rRNA G-quadruplexes in fixed HeLa cells. On the other hand, due to the retained mitochondrial membrane potential in live HeLa cells, SEMA-1 was captured by mitochondria and had the potential to detect the mitochondrial G-quadruplexes. Collectively, this work demonstrates the value of developing G-quadruplex-specific fluorescent probes from novel benzoselenazolium-based hemicyanine scaffold.
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G-Cuádruplex , Carbocianinas , Colorantes Fluorescentes , Células HeLa , HumanosRESUMEN
BACKGROUND: Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain. METHODS: We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo. RESULTS: Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1. CONCLUSIONS: The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development.
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Neoplasias Colorrectales , Complejo IV de Transporte de Electrones/metabolismo , Factor 1 de Crecimiento de Fibroblastos , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Humanos , Hipoxia/genética , Neovascularización Patológica , Microambiente Tumoral/genéticaRESUMEN
Cystic renal masses are often encountered during abdominal imaging. Although most of them are benign simple cysts, some cystic masses have malignant characteristics. The Bosniak classification system provides a useful way to classify cystic masses. The Bosniak classification is based on the results of a well-established computed tomography protocol. Over the past 30 years, the classification system has been refined and improved. This paper reviews the literature on this topic and compares the advantages and disadvantages of different screening and classification methods. Patients will benefit from multimodal diagnosis for lesions that are difficult to classify after a single examination.
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Enfermedades Renales Quísticas , Neoplasias Renales , Humanos , Riñón/diagnóstico por imagen , Enfermedades Renales Quísticas/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodosRESUMEN
OBJECTIVES: To evaluate the value of the computer-aided diagnosis system, S-Detect (based on deep learning algorithm), in distinguishing benign and malignant breast masses and reducing unnecessary biopsy based on the experience of radiologists. METHODS: From February 2018 to March 2019, 266 breast masses in 192 women were included in our study. Ultrasound (US) examination, including S-Detect technique, was performed by the radiologist with about 10 years of clinical experience in breast US imaging. US images were analyzed by four other radiologists with different experience in breast imaging (radiologists 1, 2, 3, and 4 with 1, 4, 9, and 20 years, respectively) according to their clinical experience (with and without the results of S-Detect). Diagnostic capabilities and unnecessary biopsy of radiologists and radiologists combined with S-Detect were compared and analyzed. RESULTS: After referring to the results of S-Detect, the changes made by less experienced radiologists were greater than experienced radiologists (benign or malignant, 44 vs 22 vs 14 vs 2; unnecessary biopsy, 34 vs 25 vs 10 vs 5). When combined with S-Detect, less experienced radiologists showed significant improvement in accuracy, specificity, positive predictive value, negative predictive value, and area under curve (P < .05), but not for experienced radiologists (P > .05). Similarly, the unnecessary biopsy rate of less experienced radiologists decreased significantly (44.4% vs 32.7%, P = .006; 36.8% vs 28.2%, P = .033), but not for experienced radiologists (P > .05). CONCLUSIONS: Less experienced radiologists rely more on S-Detect software. And S-Detect can be an effective decision-making tool for breast US, especially for less experienced radiologists.
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Neoplasias de la Mama , Mama , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Computadores , Diagnóstico Diferencial , Femenino , Humanos , Radiólogos , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.
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Próstata , Neoplasias de la Próstata , Consultores , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Ultrasonografía Intervencional , UrólogosRESUMEN
RNA imaging is of great importance for understanding its complex spatiotemporal dynamics and cellular functions. Considerable effort has been devoted to the development of small-molecule fluorescent probes for RNA imaging. However, most of the reported studies have mainly focused on improving the photostability, permeability, long emission wavelength, and compatibility with live-cell imaging of RNA probes. Less attention has been paid to the selectivity and detection limit of this class of probes. Highly selective and sensitive RNA probes are still rarely available. In this study, a new set of styryl probes were designed and synthesized, with the aim of upgrading the detection limit and maintaining the selectivity of a lead probe QUID-1 for RNA. Among these newly synthesized compounds, QUID-2 was the most promising candidate. The limit of detection (LOD) value of QUID-2 for the RNA was up to 1.8 ng/mL in solution. This property was significantly improved in comparison with that of QUID-1. Further spectroscopy and cell imaging studies demonstrated the advantages of QUID-2 over a commercially available RNA staining probe, SYTO RNASelect, for highly selective and sensitive RNA imaging. In addition, QUID-2 exhibited excellent photostability and low cytotoxicity. Using QUID-2, the global dynamics of RNA were revealed in live cells. More importantly, QUID-2 was found to be potentially applicable for detecting RNA granules in live cells. Collectively, our work provides an ideal probe for RNA imaging. We anticipate that this powerful tool may create new opportunities to investigate the underlying roles of RNA and RNA granules in live cells.
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Colorantes Fluorescentes , ARN , Colorantes Fluorescentes/química , Sondas ARN , Imagen MolecularRESUMEN
The industrially important methanol-to-hydrocarbons (MTH) reaction is driven and sustained by autocatalysis in a dynamic and complex manner. Hitherto, the entire molecular routes and chemical nature of the autocatalytic network have not been well understood. Herein, with a multitechnique approach and multiscale analysis, we have obtained a full theoretical picture of the domino cascade of autocatalytic reaction network taking place on HZSM-5 zeolite. The autocatalytic reaction is demonstrated to be plausibly initiated by reacting dimethyl ether (DME) with the surface methoxy species (SMS) to generate the initial olefins, as evidenced by combining the kinetic analysis, in situ DRIFT spectroscopy, 2D 13C-13C MAS NMR, electronic states, and projected density of state (PDOS) analysis. This process is operando tracked and visualized at the picosecond time scale by advanced ab initio molecular dynamics (AIMD) simulations. The initial olefins ignite autocatalysis by building the first autocatalytic cycle-olefins-based cycle-followed by the speciation of methylcyclopentenyl (MCP) and aromatic cyclic active species. In doing so, the active sites accomplish the dynamic evolution from proton acid sites to supramolecular active centers that are experimentally identified with an ever-evolving and fluid feature. The olefins-guided and cyclic-species-guided catalytic cycles are interdependently linked to forge a previously unidentified hypercycle, being composed of one "selfish" autocatalytic cycle (i.e., olefins-based cycle with lighter olefins as autocatalysts for catalyzing the formation of olefins) and three cross-catalysis cycles (with olefinic, MCP, and aromatic species as autocatalysts for catalyzing each other's formation). The unraveled dynamic autocatalytic cycles/network would facilitate the catalyst design and process control for MTH technology.
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The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, including MitoISCH, an mtDNA G4-specific fluorescent probe, together with MitoPDS, a mitochondria-targeted G4-stabilizing agent, to thoroughly investigate mtDNA G4s. Using MitoISCH to monitor previously intractable dynamics of mtDNA G4s, we surprisingly found that their formation was prevalent only in endothelial and cancer cells that rely on glycolysis for energy production. Consistent with this, promotion of mtDNA G4 folding by MitoPDS in turn caused glycolysis-related gene activation and glycolysis enhancement. Remarkably, this close relationship among mtDNA G4s, glycolysis, and cancer cells further allowed MitoISCH to accumulate in tumors and label them in vivo. Our work reveals an unprecedented link between mtDNA G4s and cell glycolysis, suggesting that mtDNA G4s may be a novel cancer biomarker and therapeutic target deserving further exploration.
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ADN Mitocondrial/metabolismo , Colorantes Fluorescentes/química , G-Cuádruplex , Glucólisis/fisiología , Células 3T3 , Animales , Línea Celular Tumoral , ADN Mitocondrial/genética , Células Endoteliales/metabolismo , Humanos , Ratones , Ratones Desnudos , Mitocondrias/metabolismoRESUMEN
Because of the lack of facile and accurate methods to track stress granule (SG) dynamics in live cells and in vivo, in-depth studies of the biological roles of this attractive membraneless organelle have been limited. Herein, we report the first small-molecule probe, TASG, for the selective, convenient and real-time monitoring of SGs. This novel molecule can simultaneously bind to SG RNAs, the core SG protein G3BP1, and their complexes, triggering a significant enhancement in fluorescence intensity, making TASG broadly applicable to SG imaging under various stress conditions in fixed and live cells, ex vivo and in vivo. Using TASG, the complicated endogenous SG dynamics were revealed in both live cells and C. elegans. Collectively, our work provides an ideal probe that has thus far been absent in the field of SG investigations. We anticipate that this powerful tool may create exciting opportunities to investigate the underlying roles of SGs in different organisms.
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Condensados Biomoleculares , Caenorhabditis elegans , Animales , ADN Helicasas , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , Gránulos de EstrésRESUMEN
Designing highly selective and cost-effective electrocatalysts toward electrochemical carbon dioxide (CO2 ) reduction is crucial for desirable transformation of greenhouse gas into fuels or high-value chemical products. Here, the authors report intermetallic Cu3 Sn that is in situ formed and seamlessly integrated on self-supported bimodal nanoporous Cu skeleton (Cu3 Sn/Cu) via a spontaneous alloying of Sn and Cu as robust electrocatalyst for selective electroreduction of CO2 to CO. By virtue of Sn atoms strengthening CO adsorption on Cu atoms, the intermetallic Cu3 Sn has an intrinsic activity of ≈10.58 µA cm-2 , more than 80-fold higher than that of monometallic Cu. By virtue of hierarchical bicontinuous nanoporous Cu architecture facilitating electron transfer and CO2 and proton mass transport and offering high specific surface areas for full use of electroactive Cu3 Sn sites, the nanoporous Cu3 Sn/Cu hybrid electrodes produce CO at a low overpotential of 0.09 V, and exhibit high partial current density of ≈15 mA cm-2 geo at overpotential of 0.59 V, along with excellent stability and selectivity of 91.5% Faradaic efficiency. The outstanding electrochemical performance make them attractive alternatives to precious Au- and Ag-based electrocatalysts for building low-cost CO2 electrolyzers to selectively produce CO.
RESUMEN
Computer-aided diagnosis (CAD) systems have attracted extensive attention owing to their performance in the field of image diagnosis and are rapidly becoming a promising auxiliary tool in medical imaging tasks. These systems can quantitatively evaluate complex medical imaging features and achieve efficient and high-diagnostic accuracy. Deep learning is a representation learning method. As a major branch of artificial intelligence technology, it can directly process original image data by simulating the structure of the human brain neural network, thus independently completing the task of image recognition. S-Detect is a novel and interactive CAD system based on a deep learning algorithm, which has been integrated into ultrasound equipment and can help radiologists identify benign and malignant nodules, reduce physician workload, and optimize the ultrasound clinical workflow. S-Detect is becoming one of the most commonly used CAD systems for ultrasound evaluation of breast and thyroid nodules. In this review, we describe the S-Detect workflow and outline its application in breast and thyroid nodule detection. Finally, we discuss the difficulties and challenges faced by S-Detect as a precision medical tool in clinical practice and its prospects.