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Attributing to the advantages of intrinsic safety, high energy density, and good omnidirectional flexibility, fiber-shaped aqueous zinc ions batteries (FAZIBs), serving as energy supply devices, have multitude applications in flexible and wearable electronic devices. However, the detachment of active materials caused by bending stress generated during flexing process limits their practical application severely. To address the above issue, an effective integrated strategy employing microcracked activated cobalt hydroxide [A-Co(OH)2] cathode with protective coating of poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate) (PEDOT:PSS) was proposed in this work to enhance the cyclic and bending performances of FAZIBs. The microcracked A-Co(OH)2 cathode relieves stress concentration under bending conditions, while the PEDOT:PSS coating is responsible to maintain the structural integrity and prevents the detachment of A-Co(OH)2. The FAZIBs based on a gel electrolyte achieved a high energy density (173.5 Wh·kg-1) at a power density 90 W·kg-1 and a bending durability (94.4 % capacity retention after 500 cycles) as a consequence of the synergistic effect of microcracked A-Co(OH)2 cathode and the PEDOT:PSS coating. This work will offer a new approach for devising high-performance FAZIBs and promote the development of highly flexible and stable fiber-shaped batteries.
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Aqueous Zn-ion batteries featuring with intrinsic safety and low cost are highly desirable for large-scale energy storage, but the unstable Zn-metal anode resulting from uncontrollable dendrite growth and grievous hydrogen evolution reaction (HER) shortens their cycle life. Herein, a feasible in situ self-reconfiguration strategy is developed to generate triple-gradient poly(diallyldimethylammonium) bis(trifluoromethanesulfonyl)imide (PDDA-TFSI)-Zn5(OH)8Cl2·H2O-Sn (PT-ZHC-Sn) artificial layer. The resulting triple-gradient interface consists of the spherical top layer PT with cation confinement and H2O inhibition, the dense intermediate layer ZHC nanosheet with Zn2+ conduction and electron shielding, and the bottom layer Znophilic Sn metal. The well-designed triple-gradient artificial interfacial layer synergistically facilitates rapid Zn2+ diffusion to regulate uniform Zn deposition and accelerates the desolvation process while suppressing HER. Consequently, the PT-ZHC-Sn@Zn symmetric cell achieves an ultralong lifespan over 6500 h at 0.5 mA cm-2 for 0.5 mAh cm-2. Furthermore, a full battery coupling with MnO2 cathode exhibits a 17.2% increase in capacity retention compared with bare Zn anode after 1000 cycles. The in situ self-reconfiguration strategy is also applied to prepare triple-gradient PT-ZHC-In, and the assembled Zn//Cu cell operates steadily for over 8400 h while maintaining Coulombic efficiency of 99.6%. This work paves the way to designing multicomponent gradient interface for stable Zn-metal anodes.
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BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.
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Clorhidrato de Duloxetina , Pramipexol , Síndrome de las Piernas Inquietas , Anciano , Femenino , Humanos , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Clorhidrato de Duloxetina/uso terapéutico , Clorhidrato de Duloxetina/efectos adversos , Fenotipo , Pramipexol/uso terapéutico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndrome de las Piernas Inquietas/inducido químicamente , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéuticoRESUMEN
Tuberculosis (TB), a deadly infectious disease induced by Mycobacterium tuberculosis (Mtb), continues to be a global public health issue that kill millions of patents every year. Despite significant efforts have been paid to identify effective TB treatments, the emergence of drug-resistant strains of the disease and the presence of comorbidities in TB patients urges us to explore the detailed mechanisms involved in TB immunity and develop more effective innovative anti-TB strategies. HIF-1α, a protein involved in regulating cellular immune responses during TB infection, has been highlighted as a promising target for the development of novel strategies for TB treatment due to its critical roles in anti-TB host immunity. This review provides a summary of current research progress on the roles of HIF-1α in TB infection, highlighting its importance in regulating the host immune response upon Mtb infection and summarizing the influences and mechanisms of HIF-1α on anti-TB immunological responses of host cells. This review also discusses the various challenges associated with developing HIF-1α as a target for anti-TB therapies, including ensuring specificity and avoiding off-target effects on normal cell function, determining the regulation and expression of HIF-1α in TB patients, and developing drugs that can inhibit HIF-1α. More deep understanding of the molecular mechanisms involved in HIF-1α signaling, its impact on TB host status, and systematic animal testing and clinical trials may benefit the optimization of HIF-1α as a novel therapeutic target for TB.
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Antituberculosos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mycobacterium tuberculosis , Transducción de Señal , Tuberculosis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/inmunología , Transducción de Señal/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , Tuberculosis/metabolismo , Tuberculosis/microbiología , Animales , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Terapia Molecular Dirigida/métodosRESUMEN
Psoriasis is a prevalent condition characterized by chronic inflammation, immune dysregulation, and genetic alterations, significantly impacting the well-being of affected individuals. Recently, a novel aspect of programmed cell death, ferroptosis, linked to iron metabolism, has come to light. This research endeavors to unveil novel diagnostic genes associated with ferroptosis in psoriasis, employing bioinformatic methods and experimental validation. Diverse analytical strategies, including "limma," Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Random Forest (RF), were employed to pinpoint pivotal ferroptosis-related diagnostic genes (FRDGs) in the training datasets GSE30999, testing dataset GSE41662 and GSE14905. The discriminative potential of FRDGs in distinguishing between normal and psoriatic patients was gauged using Receiver Operating Characteristic (ROC) curves, while the functional pathways of FRDGs were scrutinized through Gene Set Enrichment Analysis (GSEA). Spearman correlation and ssGSEA analysis were applied to explore correlations between FRDGs and immune cell infiltration or oxidative stress-related pathways. The study identified six robust FRDGs - PPARD, MAPK14, PARP9, POR, CDCA3, and PDK4 - which collectively formed a model boasting an exceptional AUC value of 0.994. GSEA analysis uncovered their active involvement in psoriasis-related pathways, and substantial correlations with immune cells and oxidative stress were noted. In vivo, experiments confirmed the consistency of the six FRDGs in the psoriasis model with microarray results. In vitro, genetic knockdown or inhibition of MAPK14 using SW203580 in keratinocytes attenuated ferroptosis and reduced the expression of inflammatory cytokines. Furthermore, the study revealed that intercellular communication between keratinocytes and macrophages was augmented by ferroptotic keratinocytes, increased M1 polarization, and recruitment of macrophage was regulated by MAPK14. In summary, our findings unveil novel ferroptosis-related targets and enhance the understanding of inflammatory responses in psoriasis. Targeting MAPK14 signaling in keratinocytes emerges as a promising therapeutic approach for managing psoriasis.
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Circular RNAs (circRNAs) have exhibited microRNA sponge activity, related to many important biological processes. Our study attempted to explore the comprehensive changes of circRNAs expression pattern in Obstructive sleep apnea (OSA)-induced liver injury and provide a global perspective of differentially expressed circRNAs (DECs). Then, RT-qPCR was used to confirm the microarray data. Further, gene ontology (GO) and KEGG pathway analysis were performed to annotate the DECs. Finally, the circRNA-miRNA-mRNA interaction network was established to predicted the target genes and target miRNAs of DECs for a stepwise bioinformatics analysis. We revealed a total of eighty DECs. In the meantime, six circRNAs were randomly validated by RT-qPCR. Among these circRNAs, mmu_circRNA_000469, 37851, 38959, 38983, 31665 were up-regulated in both microarray and qRT-PCR tissues, while mmu_circRNA_27565 was down-regulated. GO analysis revealed that circRNAs-target genes were largely related to liver function process such as carboxylic acid metabolic process and negative regulation of mitochondrial membrane potential. Meanwhile, KEGG analysis found that there were 13 pathways related to these circRNAs- target genes. And the most enriched pathway was Natural killer cell mediated cytotoxicity, which strongly suggests that immune responses may be important for the process of OSA-induced liver injury. In addition, four significant DECs (mmu_circRNA_000469, 38959, 38983, 27565) and their target mRNA and target miRNAs were further selected to establish the regulation network. Our study revealed that circRNAs may play a crucial role in OSA-induced liver injury and thus mmu_circRNA_000469, 38959, 38983, 27565 may serve as biomarkers of biological process of OSA-induced liver injury.
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ARN Circular , Apnea Obstructiva del Sueño , ARN Circular/genética , ARN Circular/metabolismo , Apnea Obstructiva del Sueño/genética , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Perfilación de la Expresión Génica , Masculino , Hígado/metabolismo , Redes Reguladoras de Genes , Animales , Biología Computacional , ARN Mensajero/metabolismo , ARN Mensajero/genética , Ontología de GenesRESUMEN
PURPOSE: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer (BC) with second primary malignancies (SPMs). MATERIALS AND METHODS: 149 BC patients (149/1419, 10.5 %) ultimately diagnosed with SPMs were included in the study. The following data were evaluated: age, location, the treatment of the first BC, the interval between the first BC and SPMs, the maximum diameter of SPMs, the maximum standardized uptake value (SUVmax) of SPMs, and SPMs metastases. The overall survival (OS) and progression-free survival (PFS) of follow-up patients were analyzed. The diagnostic efficiency of 18F-FDG PET/CT for SPMs and consistency with the pathological findings were calculated. RESULTS: The most common SPMs of BC was lung cancer (81/149, 54.4 %), particularly early-stage lung adenocarcinoma. There were the shorter maximum diameter of SPMs, the lower SUVmax of SPMs, and the fewer SPMs metastases in the lung cancer group than non-lung cancer group (P<0.001). The OS and PFS of the follow-up patients in the lung cancer group were longer than non-lung cancer group (P<0.001). The SPMs metastases was independent prognostic indicator of OS. The pathological grouping and the SPMs metastases were independent prognostic indicators of PFS. 18F-FDG PET/CT efficacy in diagnosing SPMs in BC patients was high. Compared with the pathological findings, the consistency was good (P = 0.010). CONCLUSION: Applying 18F-FDG PET/CT in BC patients might be helpful in detecting SPMs and partially predicting patient prognosis, in addition to its primary function in the diagnosis and staging of BC.
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Neoplasias de la Mama , Neoplasias Pulmonares , Neoplasias Primarias Secundarias , Humanos , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias Primarias Secundarias/diagnóstico por imagen , Pronóstico , Neoplasias Pulmonares/diagnóstico por imagen , Estudios Retrospectivos , RadiofármacosRESUMEN
Fiber-shaped aqueous zinc-ion batteries (FAZIBs) with intrinsic safety, highcapacity, and superb omnidirectional flexibility hold promise for wearable energy-supply devices. However, the interfacial separation of fiber-shaped electrodes and electrolytes caused by Zinc (Zn) stripping process and severe Zn dendrites occurring at the folded area under bending condition seriously restricts FAZIBs' practical application. Here, an advanced confinement encapsulation strategy is originally reported to construct dual-layer gel electrolyte consisting of high-fluidity polyvinyl alcohol-Zn acetate inner layer and high-strength Zn alginate outer layer for fiber-shaped Zn anode. Benefiting from the synergistic effect of inner-outer gel electrolyte and the formation of solid electrolyte interphase on Zn anode surface by lysine additive, the resulting fiber-shaped Zn-Zn symmetric cell delivers long cycling life over 800 h at 1 mA cm-2 with dynamic bending frequency of 0.1 Hz. The finite element simulation further confirms that dual-layer gel electrolyte can effectively suppress the interfacial separation arising from the Zn stripping and bending process. More importantly, a robust twisted fiber-shaped Zn/zinc hexacyanoferrate battery based on dual-layer gel electrolyte is successfully assembled, achieving a remarkable capacity retention of 97.7% after bending 500 cycles. Therefore, such novel dual-layer gel electrolyte design paves the way for the development of long-life fiber-shaped aqueous metal batteries.
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Mutation is the major cause of phenotypic innovations. Apart from DNA mutations, the alteration on RNA such as the ADAR-mediated A-to-I RNA editing could also shape the phenotype. These two layers of variations have not been systematically combined to study their collective roles in cancers. We collected the high-quality transcriptomes of ten hepatocellular carcinoma (HCC) and the matched control samples. We systematically identified HCC-specific mutations in the exonic regions and profiled the A-to-I RNA editome in each sample. All ten HCC samples had mutations in the CDS of ADAR2 gene (dsRNA-binding domain or catalytic domain). The consequence of these mutations converged to the elevation of ADAR2 efficiency as reflected by the global increase of RNA editing levels in HCC. The up-regulated editing sites (UES) were enriched in the CDS and UTR of oncogenes and tumor suppressor genes (TSG), indicating the possible roles of these target genes in HCC oncogenesis. We present the mutation-ADAR2-UES-oncogene/TSG-HCC axis that explains how mutations at different layers would finally lead to abnormal phenotype. In the light of central dogma, our work provides novel insights into how to fully take advantage of the transcriptome data to decipher the consequence of mutations.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/genética , Mutación , ARN , ARN no TraducidoRESUMEN
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive malignancy, and timely diagnosis of ESCC contributes to an increased cancer survival rate. However, current detection methods for ESCC mainly rely on endoscopic examination, limited by a relatively low participation rate. Herein, ferric-particle-enhanced laser desorption/ionization mass spectrometry (FPELDI MS) is utilized to record the serum metabolic fingerprints (SMFs) from a retrospective cohort (523 non-ESCC participants and 462 ESCC patients) to build diagnostic models toward ESCC. The PFELDI MS achieved high speed (≈30 s per sample), desirable reproducibility (coefficients of variation < 15%), and high throughput (985 samples with ≈124â¯200 data points for each spectrum). Desirable diagnostic performance with area-under-the-curves (AUCs) of 0.925-0.966 is obtained through machine learning of SMFs. Further, a metabolic biomarker panel is constructed, exhibiting superior diagnostic sensitivity (72.2-79.4%, p < 0.05) as compared with clinical protein biomarker tests (4.3-22.9%). Notably, the biomarker panel afforded an AUC of 0.844 (95% confidence interval [CI]: 0.806-0.880) toward early ESCC diagnosis. This work highlighted the potential of metabolic analysis for accurate screening and early detection of ESCC and offered insights into the metabolic characterization of diseases including but not limited to ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/diagnóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Reproducibilidad de los Resultados , Biomarcadores de TumorRESUMEN
Obesity, with complications such as type 2 diabetes, dyslipidemia, and even cancer, is rampant worldwide. Histone deacetylases (HDACs) have been extensively studied as key players in the epigenetic regulation of cellular metabolism. However, the function of HDAC11 has long been focused on the immune and nervous systems and cancer development, and its potential role in obesity has been poorly studied. We found that the expression of HDAC11 was highly upregulated in the white adipose tissue (WAT) of obese mice and was closely related to the progression of obesity. Knockdown of HDAC11 by lentiviral injection in high-fat diet-fed mice attenuated the development of obesity. Furthermore, knockdown of HDAC11 ameliorated WAT hypertrophy and induced WAT browning. At the cellular level, silencing of HDAC11 promoted the differentiation of adipose-derived stem cells (ADSCs) into brown adipocyte-like cells and inhibited the proliferation of ADSCs. More interestingly, HDAC11 expression was elevated in ADSCs isolated from obese mice, and silencing of HDAC11 facilitated the spontaneous differentiation of ADSCs into mesoderm, which is the source of adipocytes. This also superficially and effectively demonstrates the exciting prospect of HDAC11 silencing in obesity research and treatment, as a valve for "energy saving and flow reduction".
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Diabetes Mellitus Tipo 2 , Histona Desacetilasas , Neoplasias , Animales , Ratones , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Epigénesis Genética , Histona Desacetilasas/metabolismo , Ratones Endogámicos C57BL , Ratones Obesos , Neoplasias/metabolismo , Obesidad/metabolismo , Células Madre/metabolismoRESUMEN
Aqueous Zn-ion batteries offer the advantages of greater security and lower fabrication costs over their lithium-ion counterparts. However, their further advancement and practical application are hindered by the drastic decay in their performance due to the uncontrollable dendrite growth on Zn anodes. In this study, we fabricated a versatile three-dimensional (3D) interfacial layer (3D PVDF-Zn(TFO)2 (PVDF: poly(vinylidene fluoride); TFO: trifluoromethanesulfonate), which simultaneously formed porous Zn-metal anodes (PZn) with an enhanced (002) texture, via a in situ etching scheme. The 3D PVDF-Zn(TFO)2@PZn symmetrical cells leverage the advantages of surface coating and 3D porous architectures to yield extra-long cyclic lifetimes of over 5300 h (0.1 mA cm-2). The fabricated anodes were found to be compatible with MnO2 cathodes, and the resulting full batteries delivered an outstanding capacity of 336 mAh g-1 at 0.1 A g-1 and exhibited impressive long-term reversibility with a capacity retention of 78.7% for 2000 cycles. The proposed coating strategy is viable for developing porous structures with cutting-edge designs and for textured surface engineering.
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Chemotherapy often faces some obstacles such as low targeting effects and drug resistance, which introduce the low therapeutic efficiency and strong side effects. Recent advances in nanotechnology allows the use of novel nanosystems for targeted drug delivery, although the chemically synthesized nanomaterials always show unexpected low biocompability. The emergence of exosome research has offered a better understanding of disease treatment and created novel opportunities for developing effective drug delivery systems with high biocompability. Moreover, RNA interference has emerged as a promising strategy for disease treatments by selectively knocking down or over-expressing specific genes, which allows new possibilities to directly control cell signaling events or drug resistance. Recently, more and more interests have been paid to develop optimal delivery nanosystems with high efficiency and high biocompability for drug and functional RNA co-delivery to achieve enhanced chemotherapy. In light of the challenges for developing drug and RNA co-delivery system, exosomes have been found to show very attractive prospects. This review aims to explore current technologies and challenges in the use of exosomes as drug and RNA co-delivery system with a focus on the emerging trends and issues associated with their further applications, which may contribute to the accelerated developments of exosome-based theraputics.
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Aqueous rechargeable zinc ion batteries (ARZIBs) are ideal for massive and longstanding energy storage applications because of their excellent security and low operation cost. Nevertheless, ARZIBs are subject to the severe corrosion reaction of zinc metal anodes that is derived from the thermodynamic unsteadiness of the zinc anodes in aqueous solution, as well as zinc dendrite growth originating from uncontrolled zinc deposition. Herein, we created a separator by coating a thin piece of polypropylene (PP) with a compound consisting of zinc trifluoromethanesulfonate [Zn(OTf)2] and poly(vinylidene fluoride-hexafluoropropylene (PVDF-HFP). Consequently, the severe corrosion reaction of the zinc metal anodes and the profuse formation of zinc dendrites were effectively mitigated by the novel PP separator, which prolonged the lifetime of the zinc metal anodes. When a zinc metal plating layer was used with preferential (002) crystallographic orientation, the cyclic performance over 1100 h of the symmetrical Znâ¥Zn battery based on the novel separator was steady. Additionally, the Znâ¥MnO2 batteries exhibited an impressive specific capacity and competitive long durability of 75.5% over 500 cycles at a current density of 0.1 A g-1. With this work, we intend to set the standard for designing novel separators in the construction of advanced zinc anodes for high-performance ARZIBs.
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Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.
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With the transformation of modern lifestyles and population ageing, obesity has become a global epidemic, as one of the important threat to human health of chronic non-communicable diseases (NCD). Stem cell therapy seems promising as an alternative strategy for managing obesity and related metabolic problems. Adipose tissue-derived stem cells (ADSCs) have received widespread attention, which provides new ideas for the treatment of obesity and various metabolic-related diseases, due to their abundant reserves, easy acquisition, rapid expansion, and multi-directional differentiation potential, low immunogenicity and many other advantages. Accordingly, there seems to be a "shield and spear paradox" in the relationship between ADSCs and obesity. In this review, we emphatically summarized the role of ADSCs in the occurrence and development of obesity and related metabolic disease processes, in order to pave the way for clinical practice.
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The prevention and treatment of obesity have been one of the most difficult problems in the world. Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies have shown that IF could improve obesity and diabetes-related metabolic disorders. Here, we show that IF can change the composition and metabolic function of intestinal microbes, and reduce lipid absorption by inhibiting PI3K/AKT signaling pathway, with the participation of arginine. Arginine concentration in feces of fasted mice is inversely correlated with Akkermansia muciniphila abundance. Antibiotic-induced clearance of intestinal microbiota greatly inhibits the effect of IF. Furthermore, the colonization test of Akkermansia muciniphila again activates the browning of white adipose tissue and restores the improvement of metabolism to alleviate obesity. These phenomena indicate that every-other-day fasting regimen inhibits intestinal lipid absorption and promotes the browning of white adipose tissue in mice to ameliorate the risk of obesity and metabolic disorders through the microbial flora-metabolite-fat signaling axis. And the above results demonstrate new directions for the treatment of obesity and other metabolic disorders.
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Microbioma Gastrointestinal , Enfermedades Metabólicas , Animales , Ratones , Ayuno Intermitente , Fosfatidilinositol 3-Quinasas , Obesidad/metabolismo , Lípidos/farmacología , Dieta Alta en Grasa , Ratones Endogámicos C57BLRESUMEN
Purpose: Cardiotocography (CTG), which measures uterine contraction (UC) and fetal heart rate (FHR), is a crucial tool for assessing fetal health during pregnancy. However, traditional computerized cardiotocography (cCTG) approaches have non-negligible calibration errors in feature extraction and heavily rely on the expertise and prior experience to define diagnostic features from CTG or FHR signals. Although previous works have studied deep learning methods for extracting CTG or FHR features, these methods still neglect the clinical information of pregnant women. Methods: In this paper, we proposed a multimodal deep learning architecture (MMDLA) for intelligent antepartum fetal monitoring that is capable of performing automatic CTG feature extraction, fusion with clinical data and classification. The multimodal feature fusion was achieved by concatenating high-level CTG features, which were extracted from preprocessed CTG signals via a convolution neural network (CNN) with six convolution layers and five fully connected layers, and the clinical data of pregnant women. Eventually, light gradient boosting machine (LGBM) was implemented as fetal status assessment classifier. The effectiveness of MMDLA was evaluated using a dataset of 16,355 cases, each of which includes FHR signal, UC signal and pertinent clinical data like maternal age and gestational age. Results: With an accuracy of 90.77% and an area under the curve (AUC) value of 0.9201, the multimodal features performed admirably. The data imbalance issue was also effectively resolved by the LGBM classifier, with a normal-F1 value of 0.9376 and an abnormal-F1 value of 0.8223. Conclusion: In summary, the proposed MMDLA is conducive to the realization of intelligent antepartum fetal monitoring.
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Hydrazine and its derivatives are well-known environmental hazards and biological carcinogens; therefore, there is a great need for a powerful workflow solution for protecting the public from unexpected exposure to toxic contaminants. Recently, functional surface-enhanced Raman scattering (SERS) exhibits enormous benefits in sensing trace biochemical substances due to its fingerprint-like identification of individual molecules, making it an ideal method for detecting and quantifying hydrazine. Herein, for the first time, we integrated the orthogonal chemical reporter strategy with SERS to build an intelligent hydrazine detection platform (orthogonal chemical SERS, ocSERS), in which 4-mercaptobenzaldehyde was incorporated on a nanoimprinted gold nanopillar array, which acted as an orthogonal coupling partner of hydrazine to form Raman active benzaldehyde hydrazone, allowing for sensitively detecting hydrazine with a detection limit of 10-13 M in complex circumstances. Particularly, ocSERS could effectively identify the carcinogen N-nitrosodimethylamine (NDMA) after its reduction to dimethylhydrazine (UDMH), enabling ultrasensitive detection of UDMH (10-13 M). Importantly, ocSERS could not only monitor elevated levels of NDMA in ranitidine due to improper storage but also quantify NDMA in urine and blood after oral administration of NDMA-containing drugs, thereby preventing NDMA overexposure. Therefore, ocSERS represents the first click SERS sensor and may open up a new analytical field.
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Líquidos Corporales , Nanopartículas del Metal , Oro/química , Hidrazinas , Espectrometría Raman/métodos , Nanopartículas del Metal/químicaRESUMEN
AIMS: Obesity and its related metabolic disorders, including insulin resistance and fatty liver, have become a serious global public health problem. Previous studies have shown Methionine Enkephalin (MetEnk) has the potential on adipocyte browning, however, its effects on the potential mechanisms of its regulation in browning as well as its improvement in energy metabolic homeostasis remain to be deciphered. MAIN METHODS: C57BL/6J male mice were fed with high-fat diet (HFD) to induce obesity model, and MetEnk was injected subcutaneously to detect changes in the metabolic status of mice, adipocytes and HepG2 cells were also treated with MetEnk, and transcriptomic, metabolomic were used to detect the changes of lipid metabolism, mitochondrial function, inflammation and other related factors. KEY FINDINGS: We found that MetEnk effectively protected against obesity weight gain in HFD-induced C57BL/6J mice, significantly improved glucose tolerance and insulin sensitivity, reduced the expression levels of interleukin 6 (IL-6), promoted white fat browning, moreover, using a combination of transcriptomic, metabolomic and inhibitors, it was found that MetEnk improved mitochondrial function, promoted thermogenesis and lipolysis by activating cAMP/PKA pathway in adipocytes, further analysis found that MetEnk also promoted lipolysis and alleviated inflammation through AMP-activated protein kinase (AMPK) pathway in mice liver and HepG2 cells. SIGNIFICANCE: Our study provides profound evidence for the role of MetEnk in improving lipid metabolism disorders. This study provides a mechanical foundation for investigating the potential of MetEnk to improve obesity and its associated metabolic disorders.