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α-halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon-boron and carbon-halogen bonds into a broad range of carbon-X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst-free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α-halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals.
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Codonopsis pilosula polysaccharides (CPP), the main active ingredient of Codonopsis pilosula, has gained significant attention as a liver-protective agent. Previous studies have demonstrated that CPP could alleviate gut microbiota dysbiosis in colitis or obese mice. However, the effects of CPP on mycotoxin-induced liver injury and gut microbiota dysbiosis are still poorly understood. In this study, we aimed to investigate the protective effects of CPP on sterigmatocystin (STC)-induced liver injury, as well as its regulatory effects on gut microbiota. Our results revealed that CPP intervention significantly alleviated STC-induced liver injury, as evidenced by decreased liver index, reduced liver histopathological changes, and modulation of related molecular markers. Additionally, we found that CPP could alleviate liver injury by reducing liver inflammation and oxidative stress, inhibiting hepatocyte apoptosis, and regulating lipid metabolism. Notably, we also observed that CPP could alleviate STC-induced gut microbiota dysbiosis by modulating the diversity and richness of gut microbiota, suggesting that gut microbiota modulation may also serve as a mechanism for CPP-mediated remission of liver injury. In summary, our study not only provided a new theoretical basis for understanding the hepatotoxicity of STC and the protective effects of CPP against STC-induced liver injury, but also provided new perspectives for the application of CPP in the fields of food, healthcare products, and medicine.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Codonopsis , Disbiosis , Microbioma Gastrointestinal , Polisacáridos , Esterigmatocistina , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Disbiosis/tratamiento farmacológico , Codonopsis/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Masculino , Esterigmatocistina/farmacología , Estrés Oxidativo/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patologíaRESUMEN
Due to iterative matrix multiplications or gradient computations, machine learning modules often require a large amount of processing power and memory. As a result, they are often not feasible for use in wearable devices, which have limited processing power and memory. In this study, we propose an ultralow-power and real-time machine learning-based motion artifact detection module for functional near-infrared spectroscopy (fNIRS) systems. We achieved a high classification accuracy of 97.42%, low field-programmable gate array (FPGA) resource utilization of 38354 lookup tables and 6024 flip-flops, as well as low power consumption of 0.021 W in dynamic power. These results outperform conventional CPU support vector machine (SVM) methods and other state-of-the-art SVM implementations. This study has demonstrated that an FPGA-based fNIRS motion artifact classifier can be exploited while meeting low power and resource constraints, which are crucial in embedded hardware systems while keeping high classification accuracy.
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BACKGROUND: The milk fat globule membrane (MFGM) is a thin film that exists within the milk emulsion, suspended on the surface of milk fat globules, and comprises a diverse array of bioactive components. Recent advancements in MFGM research have sparked a growing interest in its biological characteristics and health-related functions. Thorough exploration and utilization of MFGM as a significant bioactive constituent in milk emulsion can profoundly impact human health in a positive manner. Scope and approach: This review comprehensively examines the current progress in understanding the structure, composition, physicochemical properties, methods of separation and purification, and biological activity of MFGM. Additionally, it underscores the vast potential of MFGM in the development of additives and drug delivery systems, with a particular focus on harnessing the surface activity and stability of proteins and phospholipids present on the MFGM for the production of natural emulsifiers and drug encapsulation materials. KEY FINDINGS AND CONCLUSIONS: MFGM harbors numerous active substances that possess diverse physiological functions, including the promotion of digestion, maintenance of the intestinal mucosal barrier, and facilitation of nerve development. Typically employed as a dietary supplement in infant formula, MFGM's exceptional surface activity has propelled its advancement toward becoming a natural emulsifier or encapsulation material. This surface activity is primarily derived from the amphiphilicity of polar lipids and the stability exhibited by highly glycosylated proteins.
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Glucolípidos , Glicoproteínas , Lactante , Humanos , Emulsiones , Glucolípidos/química , Glicoproteínas/química , Proteínas de la Leche/química , Gotas Lipídicas , EmulsionantesRESUMEN
This paper provides a concise review of learning-based motion artifacts (MA) processing methods in functional near-infrared spectroscopy (fNIRS), highlighting the challenges of maintaining optimal contact during subject movement, which can lead to MA and compromise data integrity. Traditional strategies often result in reduced reliability of the hemodynamic response and statistical power. Recognizing the limited number of studies focusing on learning-based MA removal, we examine 315 studies, identifying seven pertinent to our focus area. We discuss the current landscape of learning-based MA correction methods and highlight research gaps. Noting the absence of standard evaluation metrics for quality assessment of MA correction, we suggest a novel framework, integrating signal and model quality considerations and employing metrics like ΔSignal-to-Noise Ratio (ΔSNR), confusion matrix, and Mean Squared Error. This work aims to facilitate the application of learning-based methodologies to fNIRS and improve the accuracy and reliability of neurovascular studies.
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Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) with a complicated pathogenesis and limited treatments. Parthenolide (PTL), a recognized nuclear factor-κB (NF-κB) inhibitor extracted from Tanacetum balsamita, has been widely used to treat various inflammatory diseases and has been proven to improve peritoneal fibrosis in PD mice by selectively inhibiting the phosphorylation of Smad2/3. Transforming growth factor-ß1 (TGF-ß1), via Smad-dependent signaling, has a pivotal role in promoting pathogenic of fibrosis. To investigate whether PTL can inhibit peritoneal fibrosis, we affected the interaction between NF-κB and the TGF-ß/Smad2/3 pathway. Long dwell peritoneal dialysis fluid (PDF) and peritoneum tissues were collected from continuous ambulatory peritoneal dialysis (CAPD) patients. PTL was administered intragastrically into a PD mouse model by daily infusion of 4.25% dextrose-containing PDF. Treated HMrSV5 cells or rat peritoneal mesothelial cells (RPMCs) were treated with high glucose(138 mM) at the same concentration as 2.5% dextrose-containing PDF and PTL. PD-related peritoneal fibrosis samples indicated an increase in inflammation, and PTL decreased the levels of inflammatory cytokines (L-6, TNF-α, and MCP-1). PTL inhibited high glucose-induced mesothelial-to-mesenchymal transition (MMT), as indicated by a reduced expression of fibrosis markers (fibronectin, collagen I, and α-SMA) and increased expression of the epithelial marker E-cadherin. PTL also significantly decreased TGF-ß1 expression and the phosphorylation of IκBα and NF-κBp65. The changes in the levels of TGF-ß1 expression and p-p65 or p65 showed similar trends according to western blot, immunohistochemistry, and immunofluorescence assays in vitro and in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to confirm that PTL regulates the transcription of TGF-ß1 induced by high glucose through NF-κBp65. In summary, PTL induces a therapeutic effect in peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.
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Fibrosis Peritoneal , Ratas , Ratones , Animales , Fibrosis Peritoneal/tratamiento farmacológico , Fibrosis Peritoneal/patología , FN-kappa B/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Peritoneo/metabolismo , Soluciones para Diálisis , Inflamación/metabolismo , Fibrosis , Glucosa , Transición Epitelial-MesenquimalRESUMEN
Dexmedetomidine (DEX) is a highly selective α2 receptor agonist that is routinely used in the clinic for sedation and anesthesia. Recently, an increasing number of studies have shown that DEX has a protective effect against brain injury caused by traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), cerebral ischemia and ischemia-reperfusion (I/R), suggesting its potential as a neuroprotective agent. Here, we summarized the neuroprotective effects of DEX in several models of neurological damage and examined its mechanism based on the current literature. Ultimately, we found that the neuroprotective effect of DEX mainly involved inhibition of inflammatory reactions, reduction of apoptosis and autophagy, and protection of the blood-brain barrier and enhancement of stable cell structures in five way. Therefore, DEX can provide a crucial advantage in neurological recovery for patients with brain injury. The purpose of this study was to further clarify the neuroprotective mechanisms of DEX therefore suggesting its potential in the clinical management of the neurological injuries.
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The regulation of C/N in aquaculture water is an important means of environmental regulation, of which the most common is bioflocs technology (BFT). Here, an eight-week feeding experiment and a lipopolysaccharide (LPS) challenge test were proceed to investigate the growth, oxidative stress, immunosuppression and GR-NF-κB related genes expression of Channa argus rearing in the BFT. Four groups were set, the control group was a basic diet (C/N = 7.6:1), and the other three groups were adjusted by glucose, which was C/N 10: 1, C/N 15: 1 and C/N 20:1, respectively. And we detected the two-stage test indexes of C. argus before and after the LPS challenge. The results showed that the bioflocs of C/N 15:1 group significantly (P < 0.05) promoted the growth performance. Similarly, the trend of immune enzyme activity was the same before and after LPS challenge, but decreased after challenge (except AKP and IgM). The best group is still treatment C/N 15:1. Liver and intestine SOD, CAT, GPX, ASA and T-AOC levels of juveniles in treatment C/N 15:1 were markedly increased (P < 0.05) compared to control before and after the LPS challenge. Simultaneously, the content of MDA in control group was considerably higher than that in treatment C/N 15:1 (P < 0.05). Furthermore, C/N 15:1 group significantly down-regulated the expression level of pro-inflammatory factors (NF-κB, TNF-α, IL-1ß and IL-8), and up-regulated IκBα, GR, HSP70 and HSP90 expression levels considerably (P < 0.05). Also, intestinal morphology appeared injury in control group, while intestinal integrity was better in treatment C/N 10:1 and C/N 15:1 after challenge. Taken together, these upshot indicated that bioflocs could enhance growth and alleviate C. argus from LPS-induced oxidative stress, immunosuppression and inflammation through restraining GR-NF-κB signaling pathway. The best C/N ratio for alleviating LPS is 15:1.
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Alimentación Animal/análisis , Acuicultura/métodos , Peces/crecimiento & desarrollo , Terapia de Inmunosupresión/veterinaria , Inflamación/inducido químicamente , Lipopolisacáridos/toxicidad , Animales , Antioxidantes/metabolismo , Dieta/veterinaria , Peces/inmunología , Regulación de la Expresión Génica , Estrés Oxidativo , Agua/químicaRESUMEN
Manganese (Mn) is a relatively common element in aquatic ecosystems and can be bio-concentration, but the mechanism of manganese poisoning on fish health is unclear. Here, this study's objective was to evaluate the potential mechanisms of bioflocs in ameliorating Mn-induced toxicity in Channa asiatica. Three hundred sixty juveniles were randomly divided into 12 tanks. Four C:N ratios in triplicate tanks were tried: C/N = 7.6:1 with a commercial diet (control), C/N 10:1, C/N 15:1 and C/N 20:1, and the bio-accumulation, immunotoxic, oxidative stress, GR-NF-κB related genes expression and intestinal histomorphology were assessed in three different periods after Mn exposure (0 h, 48 h and 96 h). The results showed that bioflocs had a significant protective effect on Mn poisoning by preventing alterations in bio-accumulation levels, LSZ, AKP, C3, C4 and IgM, of which the C/N 15:1 group had the best relief effect. Furthermore, bioflocs also assisted in the recovery of liver T-SOD, CAT, GPX and T-AOC levels while decreasing the content of MDA. Moreover, C/N 15:1 group significantly down-regulated the expression level of NF-κB, TNF-α, IL-1ß and IL-8 and up-regulated significantly IκBα, GR, HSP70 and HSP90 expression levels considerably (P < 0.05). From the intestinal section, the C/N 15:1 group resistance was the best one, and there was no difference between C/N 20:1 group and control group. These results revealed that administration of bioflocs (C/N 15:1) has the potential to combat Mn toxicity in C. asiatica, and the specific pathway may be GR-NF-κB.
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Proteínas de Peces/metabolismo , Peces/metabolismo , Inflamación/inducido químicamente , Manganeso/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Acuicultura , BioacumulaciónRESUMEN
Autophagy is a tightly-regulated multi-step process involving the lysosomal degradation of proteins and cytoplasmic organelles. Central to this process is the formation of the autophagosome, a double membrane-bound vesicle, which is fuse with lysosomes or endosomes, and then deliver its cytoplasmic cargo to the lysosomes. Here, we summarize the recent process of autophagy, focusing on protein molecules, their complexes, and its essential roles of autophagy in various phases. Emerging evidence has revealed that miRNAs, lncRNAs, and circRNAs play an indispensable role in autophagy regulation by modulating targeting gene expression. This review we will summarize the main features of ncRNAs and point to gaps in our current knowledge of the connection between ncRNAs and autophagy, as well as their potential utilization in various disease phenotypes. Also, we highlight recent advances in ncRNAs and autophagy-associated protein interaction and how they regulate the autophagy process.
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Proteínas Relacionadas con la Autofagia/genética , Autofagia/genética , Regulación de la Expresión Génica/genética , ARN no Traducido/genética , Animales , HumanosRESUMEN
Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well-organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post-transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA-based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy-related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.