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Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells in the nervous system. Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum. Previously, lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis; however, recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system. In addition to their role in regulating cell metabolism, lipid droplets play a protective role in various cellular stress responses. Furthermore, lipid droplets exhibit specific functions in neurons and glial cells. Dysregulation of lipid droplet formation leads to cellular dysfunction, metabolic abnormalities, and nervous system diseases. This review aims to provide an overview of the role of lipid droplets in the nervous system, covering topics such as biogenesis, cellular specificity, and functions. Additionally, it will explore the association between lipid droplets and neurodegenerative disorders. Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
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Microbial exopolysaccharides (EPSs) have attracted extensive attention for their biological functions in antioxidant activities. In this study, we characterized a novel EPS produced by Bifidobacterium pseudocatenulatum Bi-OTA128 which exhibited the highest antioxidant capacity compared to nine other ropy bacterial strains, achieving 76.50â¯% and 93.84â¯% in DPPH· and ABTS·+ scavenging activity, and ferric reducing power of 134.34⯵M Fe2+. Complete genomic analysis identified an eps gene cluster involved in the EPS biosynthesis of Bi-OTA128 strain, which might be responsible for its ropy phenotype. The EPS was then isolated and purified by a DEAE-Sepharose Fast Flow column. A single elution part EPS128 was obtained with a recovery rate of 43.5 ± 1.78â¯% and a total carbohydrate content of 93.6 ± 0.76â¯%. Structural characterization showed that EPS128 comprised glucose, galactose, and rhamnose (molar ratio 4.0:1.2:1.1), featuring a putative complex backbone structure with four branched chains and an unusual acetyl group at O-2 of terminal rhamnose. Antioxidant assay in vitro indicated that EPS128 exhibited antioxidant potential with 50.52â¯% DPPH· and 65.40â¯% ABTS·+ scavenging activities, reaching 54.3â¯% and 70.44â¯% of the efficacy of standard Vitamin C at 2.0â¯mg/L. Furthermore, EPS128 showed protective effects against H2O2-induced oxidative stress in HepG2 cells by reducing cellular reactive oxygen species (ROS) and increasing cell viability. These findings present the first comprehensive report of an antioxidant EPS from B. pseudocatenulatum, highlighting its potential as a natural antioxidant for applications in the food industry and clinical settings.
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We previously reported that a bioactive peptide (pep3) can potently inhibit the enzyme activity of purified calcineurin (CN). In this paper, we further demonstrate that transfected pep3 can strongly inhibit CN enzyme activity in HEK293 cells. Transcription factor EB (TFEB) plays an important role in the autophagy-lysosome pathway (ALP) as one of the substrates of CN, so we study the effect of pep3 on the CN-TFEB-ALP pathway. Pep3 can significantly inhibit the mRNA levels of the TFEB downstream genes and the expression of the autophagy-associated proteins, and autophagy flux in HEK293 cells. We also validated the inhibitory effect of pep3 on autophagy in mice. These findings may provide a new idea for discovering more CN inhibitors and autophagy inhibitory drugs.
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Pain catastrophizing is a prominent psychological factor that is strongly correlated with pain. Although the complex properties of pain catastrophizing vary across different pain phases, the contribution of chronic pain to its progression from a general trait to a higher state remains unclear. This study aimed to examine the neural mechanisms and degree to which pain catastrophizing is reinforced in the context of primary dysmenorrhea (PDM), one of the most prevalent gynaecological complaints experienced by women of reproductive age. Altogether, 29 women with moderate-to-severe PDM were included in this study. Arterial spin labelling was used to quantify the cerebral blood flow (CBF) in each participant in both the pain-free and painful phases. The pain catastrophizing scale (PCS) was completed in two phases, and the Short-Form McGill Pain Questionnaire was completed in the painful phase. Compared with pain catastrophizing in the pain-free phase (PCSpf), pain catastrophizing in the painful phase (PCSp) is higher and positively correlated with the composite factor of menstrual pain. CBF analysis indicated that the PCSp is positively associated with CBF in the frontal cortex, hippocampus and amygdala. The reinforcement of pain catastrophizing correlates with CBF in the prefrontal cortex. Specifically, the medial prefrontal cortex, which correlates with pain state, plays a crucial role in mediating the reinforcing effect of pain in the PCSp. These results promote the mechanical comprehension of pain catastrophizing management in individuals with chronic pain.
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In this research, the essential oils (EOs) from different parts of Ocimum gratissimum var. suave were chemically characterized and evaluated for insecticidal activity, especially against two common storage pests of Chinese herbal medicines: Tribolium castaneum and Liposcelis bostrychophila. Ocimum gratissimum is a plant with several medicinal values in traditional Chinese medicine. In the study, EOs were successfully extracted from inflorescences (OGI) and stem-leaf (OGLS) parts of O. gratissimum by steam distillation and 16 compounds were identified by gas chromatography-mass spectrometry (GC-MS), of which eugenol was the major constituent in both extracts. In fumigation toxicity tests against both pests, the EOs showed limited toxicity against T. castaneum but showed better toxicity against L. bostrychophila. Contact toxicity tests showed that OGLS had better insecticidal potential than OGI, while the insecticidal effect of eugenol sometimes exceeded that of EOs. In addition, repellency experiments showed that O. gratissimum EOs repelled the pests to varying degrees, with the effect being influenced by concentration and exposure time. The results suggest that O. gratissimum EOs could be a promising alternative to synthetic insecticides for sustainable utilization.
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Recurrent miscarriage (RM) is a chronic and heterogeneous pregnancy disorder lacking effective treatment. Alterations at the maternal-fetal interface are commonly observed in RM, with the loss of certain cell subpopulations believed to be a key cause. Through single-cell sequencing of RM patients and healthy donors, we aim to identify aberrancy of cellular features in RM tissues, providing new insights into the research. Natural killer (NK) cells, the most abundant immune cells in the decidua, are traditionally classified into dNK1, dNK2, and dNK3. In this study, we identified a new subset, dNK1/2, absent in RM tissues. This subset was named because it expresses biomarkers of both dNK1 and dNK2. With further analysis, we discovered that dNK1/2 cells play roles in immunoregulation and cytokine secretion. On the villous side of the interface, a notable decrease of extravillous trophoblast (EVT) cells was identified in RM tissues. We clustered EVTs into EVT1 (absent in RM) and EVT2 (retained in RM). Pseudotime analysis revealed distinct differentiation paths, identifying CCNB1, HMGB1, and NPM1 as EVT1 biomarkers. Additionally, we found that EVT1 is involved in the regulation of cell death, while EVT2 exhibited more angiogenic activity. Cell communication analysis revealed that interaction between EVT1 and dNK1/2 mediates chemotaxis and endothelial cell regulation, crucial for spiral artery remodeling. The loss of this interaction may impair decidualization, which is associated with RM. In summary, we propose that the loss of dNK1/2 and EVT1 cells is a significant pathological feature of RM.
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Postoperative adhesion is a common clinical disease caused by surgical trauma, accompanying serious subsequent complications. Current non-surgical drug therapy and biomaterial barrier administration have limited therapeutic effects due to their inherent deficiencies. Therefore, developing a simple, effective, and feasible method to effectively prevent postoperative adhesions after surgical procedures remains a challenge. An injectable chondroitin sulfate complex hydrogel was prepared based on aldehyde-modified chondroitin sulfate (ChS-CHO) and hydrazine-modified chondroitin sulfate (ChS-ADH). The hydrogel showed enhanced strength and good self-healing ability. By using the Schiff base reaction principle that aldehyde group reacts with hydrazide to form hydrazone bond, C-A hydrogel physical barrier is formed at the wound site to reduce the occurrence of postoperative adhesion. There is no use of chemical crosslinkers in the whole reaction system to prepare C-A hydrogel, which has excellent biocompatibility and is safe and non-toxic. The results showed that C-A hydrogel showed excellent mechanical properties, good self-healing, and biocompatibility. The cecal-abdominal wall adhesion model and hepatic adhesion model of rats were constructed respectively to evaluate its preventive effect on postoperative adhesion. The results showed that C-A hydrogel had a more significant preventive effect on postoperative adhesion, and appears to be a promising candidate for postoperative adhesion.
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BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. RESULTS: In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. CONCLUSIONS: Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.
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Background: Hemoglobin (HGB) was the most important factors which could cause dysmenorrhea in women. Metals exposure and hemoglobin level in dysmenorrhea female was unclear. We aimed to explore the associations of multi-metal exposure and HGB level in female college students with dysmenorrhea. Methods: 253 female students who had dysmenorrhea was included in our study. The Last Absolute Shrinkage and Selection Operator (LASSO) regression, generalized linear model (GLM), and Bayesian Kernel Machine Regression (BKMR) models were used to explore the associations of multi-metal exposure and HGB levels in female college students with dysmenorrhea. Results: GLM results showed that plasma Fe, Ni and Rb was positively associated with HGB and plasma Co was negatively associated with HGB. In menarche age ≤13 years old group, plasma Co and Rb only was negatively and positively associated with HGB level, respectively, and plasma Ni had positive association with HGB level in menarche age >13 years old group. BKMR results showed the reverse U-shaped relationship between the five metals mixture (Co, Fe, Ni, Cu and Rb) and HGB levels in overall and menarche age ≤13 years old group. However, there were positive association between the five metals mixture and HGB levels in menarche age >13 years old group. Conclusion: Our present study revealed that metals (Fe, Ni, Co, Rb, Cu) mixture exposure could effect HGB levels in female college students with dysmenorrhea. And the relationships were different during different menarche age in female college students.
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Ru-based electrocatalysts hold great promise for developing affordable proton exchange membrane (PEM) electrolyzers. However, the harsh acidic oxidative environment of the acidic oxygen evolution reaction (OER) often causes undesirable overoxidation of Ru active sites and subsequent serious activity loss. Here, we present an ultrathin and conformal depletion layer attached to the Schottky heterojunction of core/shell RuCo/RuCoOx that not only maximizes the availability of active sites but also improves its durability and intrinsic activity for acidic OER. Operando synchrotron characterizations combined with theoretical calculations elucidate that the lattice strain and charge transfer induced by Schottky heterojunction substantially regulate the electronic structures of active sites, which modulates the OER pathway and suppresses the overoxidation of Ru species. Significantly, the closed core/shell architecture of the RuCo/RuCoOx ensures the structure integrity of the Schottky heterojunction under acidic OER conditions. As a result, the core/shell RuCo/RuCoOx Schottky heterojunction exhibits an unprecedented durability up to 250 0 h at 10 mA cm-2 with an ultralow overpotential of â¼170 mV at 10 mA cm-2 in 0.5 M H2SO4. The RuCo/RuCoOx catalyst also demonstrates superior durability in a proton exchange membrane (PEM) electrolyzer, showcasing the potential for practical applications.
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Nitrocyclohexane (NCH) hydrogenation to cyclohexanone oxime (CHO) is of great significance in the production of caprolactam. In this work, CuFeAl-Layered Double Hydroxide (CuFeAl-LDH) catalysts with lamellar structure were prepared by co-precipitation method and applied for NCH hydrogenation, and the promoting role of FeOx was discussed. It was found that FeOx species promote the reduction of Cu2+ and control the ratio of Cu+ to Cu0. In situ DRIFT and density-functional theory (DFT) calculation results confirm that the presence of FeOx species can act as lewis base site to reduce the acid sites and facilitate the isomerization of nitrosocyclohexane to CHO, and promotes the adsorption of NCH and the desorption of the formed CHO to prevent its further reaction to form byproducts. CuFe0.05Al shows the best catalytic performance of 100 % NCH conversion and 93.35 % selectivity to CHO under mild conditions. This work provides a new idea for the design of non-noble metal-based catalysts with high activity for the selective hydrogenation of nitro compounds.
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Background and aims: Hepatic perivascular epithelioid cell tumor (PEComa) is a rare type of mesenchymal neoplasm and lacks systematic reports. The aim was to analyze the features of hepatic PEComa in order to provide our own experience for diagnosis and management from a single center. Methods: We retrospectively analyzed clinical data, imaging findings, pathology, treatments and prognosis of 36 patients with hepatic PEComa in the First Affiliated Hospital of Zhengzhou University from January 2016 to September 2023. Results: 29 females and 7 males (median age, 47.8 years) were included in this study. The majority (26/36, 72.2%) of patients were diagnosed incidentally with non-specific symptoms. Abnormal enhancement of enlarged blood vessels (27/36,75%) can be observed on CT/MRI and only 7 patients (19.4%) were correctly diagnosed by imaging examinations. The positive immunohistochemical expressions were HMB-45(35/36,97.2%), Melan-A (34/35,97.1%), SMA (23/26,88.5%) and CD34(86.7%,26/30). Treatments include resection (24/36,67.7%), radiofrequency ablation (6/36,16.7%), transcatheter arterial chemoembolization(1/36,2.7%), conservative clinical follow-up(2/36,5.6%), and sirolimus-chemotherapy (3/36,8.3%). During the follow-up period (range, 2-81 months), except for one patient with a single intrahepatic recurrence and 3 malignant patients died in 6 months, the remaining patients had no signs of recurrence and metastasis. Conclusions: Hepatic PEComa has no specific clinical features and mainly depends on clinicopathological characteristics for accurate diagnosis. Resection is the best treatment for benign PEComa, but TACE and radiofrequency ablation can also be considered in case of contraindications for surgery.
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Single-bonded polymeric nitrogen has gained tremendous research interest because of its unique physical properties and great potential applications. Despite much progress in theoretical predictions, it is still challenging to experimentally synthesize polynitrogen compounds with novel all-single-bonded units. Herein, we have synthesized two brand-new lanthanum supernitrides LaN8, through a direct reaction between La and N2 in laser-heated diamond anvil cells at megabar pressures. Our experiments and calculations revealed that two LaN8 phases had the R-3 and P4/n symmetry characterized by a unique 2D network with N18 macro-rings and cagelike N8 building blocks, respectively. Differing from known polynitrogen structures, these two polymers were composed of single-bonded nitrogen atoms belonging to sp3 and sp2 hybridizations. In particular, P4/n LaN8 possessed the longest N-N bond length among all of the experimentally reported metal nitrides, potentially being a high-energy-density material. The present study opens a fresh, promising avenue for the rational design and discovery of new supernitrides with unique nitrogen structures via the high-pressure treatment.
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PURPOSE: Explore factors influencing pain management among female breast cancer survivors aged 65+ years with moderate to severe pain based on a score of 4 or greater on the 0-10 numeric rating scale. DESIGN: Qualitative descriptive study. METHODS: We interviewed 21 purposefully sampled women aged 65+ years who experienced moderate to severe pain. Researchers coded interview transcripts for factors affecting study participants' pain management experiences. RESULTS: Pain management facilitators included patient-centered interactions with care teams and reliance on psychosocial assets. Challenges included ineffective care team interactions and participants' negative perceptions of opioid analgesia. Other factors included pain attributed to cancer treatment, pain management plan adherence, and psychosocial influencers. CONCLUSIONS: With regard to this sample, patient-centered communication and pain management education help female breast cancer survivors aged 65+ years manage their pain. Mitigation of opioid stigma and undermanaged painful comorbid conditions could further optimize pain management. Further research on the effects of breast cancer treatment, level of adherence to pain management recommendations, and psychosocial influences on pain management is needed. CLINICAL IMPLICATIONS: Providing contact information for care team members during and after clinic hours facilitates open communication, including timely reporting of new and undertreated pain. Collaborating with the patient and care team on a clear pain management plan and establishing parameters for when to notify the care team empower patients to optimize management of their pain. Verifying patients' understanding of prescribed analgesia and management of side effects and providing education as needed may reduce negative perceptions of opioid analgesia.
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Carbon quantum dots (CQDs) are ideal fluorescent probes for rapid detection. This paper reviews the synthesis methods of CQDs, their application in the rapid detection of antibiotics and heavy metals in the environment and food, and the underlying detection mechanisms. The hydrothermal method is the most commonly used for synthesis, and CQDs doped with heteroatoms (such as N, P and S) exhibit superior fluorescence performance. In the presence of antibiotics and heavy metals, the fluorescence of CQDs can be quenched or enhanced. Single-signal and dual-signal probes can be developed using the fluorescence, phosphorescence and absorbance of CQDs, enabling rapid detection of various antibiotics (e.g., tetracycline, quinolone and beta-lactam antibiotics) and heavy metals (e.g., Cd2+, Cr6+, Fe3+, Hg2+, and Pb2+). With the combination of smartphones and fluorescent probe test strips developed based on CQDs, on-the-spot rapid detection can be realized. This review offers new insights into the rapid detection of CQDs.
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Insect infestations continually endanger stored goods, underscoring the significance of discovering eco-friendly insecticides for pest management. Essential oils (EOs) from different parts of Toddalia asiatica (leaf, fruit and branch) were extracted by hydrodistillation and analyzed by GC-MS. Carvene, p-cymene and muurolene are the principal compounds of T. asiatica leaf (TAL), T. asiatica fruit (TAF) and T. asiatica branch (TAB) EO respectively. Our work aimed to assess the contact toxicity and repellent effects of EOs on two storage pests, Tribolium castaneum and Lasioderma serricorne. All tested EOs exhibited obvious contact toxicity, especially, TAL EO against T. castaneum (33.48â µg/adult) and TAF EO against L. serricorne (16.42â µg/adult). Repellency tests revealed that TAL and TAF EOs, at a concentration of 78.63â nL/cm2, achieved nearing 100 % efficiency against T. castaneum. These results suggest that EOs of T. asiatica could be used as effective botanical insecticides for managing stored-product insects.
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Background: To explore the correlation between left atrial appendage morphology, blood flow velocity and plasma galectin-3 and thrombosis in patients with atrial fibrillation. Methods: Patients with atrial fibrillation who received treatment and completed ultrasound examination in hospital from 2022 to December 2023 were enrolled. According to whether there was left atrial appendage thrombosis, the patients were divided into a control group (no left atrial appendage thrombosis was found) and a study group (left atrial appendage thrombosis was found). The morphology and structure of the left atrial appendage, blood flow velocity and plasma galectin-3 level were recorded exploring its correlation with left atrium thrombosis. Results: A total of 330 patients with atrial fibrillation were enrolled, including 278 in the control group and 52 in the study group. Left group and the control group of morphological structure differences (P < 0.05). The main lobe length, ostial area, longest diameter, shortest diameter, left atrial appendage volume and left atrial volume in the study group were higher than those in the control group (P < 0.05). The left atrial appendage emptying velocity, filling velocity and left ventricular ejection fraction of the study group were lower than those of the control group, and the left ventricular end-diastolic diameter was higher than that of the control group (P < 0.05). Group of white blood cell count, neutrophils/lymphocyte ratio, plasma galactose lectin-3 levels were higher than control group (P < 0.05). ROC curve analysis of left atrial appendage emptying velocity, left atrial appendage filling velocity, left atrial enddiastolic diameter and left atrial ejection fraction had higher diagnostic value (P < 0.05). Conclusions: Left atrial appendage morphology, blood flow velocity and plasma galectin-3 level are important factors to evaluate the risk of left atrial appendage thrombosis in patients with atrial fibrillation. This study improves the understanding of thrombosis, further elucidates the risk factors for thrombosis, and improves patient prognosis.
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The early detection of bacterial species plays a crucial role in patient prognosis and the development of effective therapeutic regimens. This study introduces an accessible and promising colorimetric sensor array designed to classify gram-positive (G+) and gram-negative (G-) bacterial species. The classification relies on 6 chemical ligands with dimethylamino/amino groups as sensing elements and silver nanotriangles as colorimetric probes. Using these specific sensor arrays, we successfully differentiated G- and G+ bacterial species and discriminated individual bacterial strains, and the sensors exhibited remarkable reproducibility and high sensitivity. Moreover, the sensor array can identify bacterial mixtures and bacteria at varying concentrations, underscoring its versatility. In summary, this sensor array offers an effective tool for bacterial analysis with promising applications in the field of biomedical diagnostics.
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Colorimetria , Ligantes , Colorimetria/métodos , Prata/química , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Nanopartículas Metálicas/química , Reprodutibilidade dos TestesRESUMO
Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.
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Desenho de Fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Animais , Humanos , Camundongos , Relação Estrutura-Atividade , Masculino , Hipoglicemiantes/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Receptores de Glucagon/agonistas , Receptores de Glucagon/metabolismoRESUMO
Water constitutes the most prevalent impurity in organic solvents, exerting significant influence on chemical reactions and potentially leading to fires and explosions, even in minute quantities. Thus, the development of convenient, rapid, and cost effective fluorescent probes for real-time monitoring of water content in organic solvents is imperative. Although some fluorescent materials have been synthesized for this purpose, most suffer from laborious preparation processes and poor cycling performance, constraining their practical application. This study investigates the impact of hydrogen bonding on the aggregation-induced emission (AIE) properties of quinoline derivatives, leveraging quinoline as the foundational scaffold and its nitrogen atom as the hydrogen bond acceptor. Research findings elucidate that intermolecular hydrogen bonding of quinoline is the primary determinant of their AIE behaviors. By harnessing the phenomenon of water molecules forming intermolecular hydrogen bonds with quinoline nitrogen atoms, we devised a straightforward and rapid method to fabricate a fluorescent test paper for real-time monitoring of water content in organic solvents. Experimental results demonstrate that even minute changes in water content, down to concentrations as low as 0.5 % by volume in organic solvents, can induce fluorescence changes in the test paper, which also exhibits favorable cycling performance. This study not only explores the influence of hydrogen bonds on the AIE properties of quinoline derivatives but also pioneers the development of a cost-effective, rapid, and recyclable test paper for real-time monitoring of water content fluctuations in organic solvents.