ABSTRACT
Adipogenesis, a pivotal cellular process involving the differentiation of mesenchymal stem cells (MSCs) to mature adipocytes, plays a significant role in various physiological functions. Dysregulation of adipogenesis is implicated in conditions such as obesity. However, the complete molecular understanding of adipogenesis remains elusive. This study aimed to uncover the novel role of lamina-associated polypeptide 2 alpha (LAP2α) in human adipose-derived stem cells (hASCs) adipogenesis and its impact on high-fat diet (HFD)-induced obesity and associated metabolic disturbances. LAP2α expression was assessed during the adipogenic differentiation of hASCs using RT-qPCR and western blotting. The functional role of LAP2α in adipogenesis was explored both in vitro and in vivo through loss- and gain-of-function studies. Moreover, mice with HFD-induced obesity received lentivirus injection to assess the effect of LAP2α knockdown on fat accumulation. Molecular mechanisms underlying LAP2α in adipogenic differentiation were investigated using RT-qPCR, Western blotting, immunofluorescence staining, and Oil Red O staining. LAP2α expression was upregulated during hASCs adipogenic differentiation. LAP2α knockdown hindered adipogenesis, while LAP2α overexpression promoted adipogenic differentiation. Notably, LAP2α deficiency resisted HFD-induced obesity, improved glucose intolerance, mitigated insulin resistance, and prevented fatty liver development. Mechanistically, LAP2α knockdown attenuated signal transducer and activator of transcription 3 (STAT3) activation by reducing the protein level of phosphorylated STAT3. A STAT3 activator (Colivelin) counteracted the negative impact of LAP2α deficiency on hASCs adipogenic differentiation. Taken together, our current study established LAP2α as a crucial regulator of hASCs adipogenic differentiation, unveiling a new therapeutic target for obesity prevention.
Subject(s)
Adipogenesis , Diet, High-Fat , Mesenchymal Stem Cells , Obesity , Humans , Diet, High-Fat/adverse effects , Obesity/metabolism , Obesity/genetics , Obesity/etiology , Animals , Mice , Mesenchymal Stem Cells/metabolism , Male , Cell Differentiation , Mice, Inbred C57BL , Adipose Tissue/metabolism , Adipose Tissue/cytology , Adipocytes/metabolism , Cells, Cultured , Gene Knockdown Techniques , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , DNA-Binding Proteins , Membrane ProteinsABSTRACT
Novel 2D materials with low-symmetry structures exhibit great potential applications in developing monolithic polarization-sensitive photodetectors with small volume. However, owing to the fact that at least half of them presented a small anisotropic factor of ≈2, comprehensive performance of present polarization-sensitive photodetectors based on 2D materials is still lower than the practical application requirements. Herein, a self-driven photodetector with high polarization sensitivity using a broken-gap ReSe2/SnSe2 van der Waals heterojunction (vdWH) is demonstrated. Anisotropic ratio of the photocurrent (Imax/Imin) could reach 12.26 (635 nm, 179 mW cm-2). Furthermore, after a facile combination of the ReSe2/SnSe2 device with multilayer graphene (MLG), Imax/Imin of the MLG/ReSe2/SnSe2 can be further increased up to13.27, which is 4 times more than that of pristine ReSe2 photodetector (3.1) and other 2D material photodetectors even at a bias voltage. Additionally, benefitting from the synergistic effect of unilateral depletion and photoinduced tunneling mechanism, the MLG/ReSe2/SnSe2 device exhibits a fast response speed (752/928 µs) and an ultrahigh light on/off ratio (105). More importantly, MLG/ReSe2/SnSe2 device exhibits excellent potential applications in polarized imaging and polarization-coded optical communication with quaternary logic state without any power supply. This work provides a novel feasible avenue for constructing next-generation smart polarization-sensitive photodetector with low energy consumption.
ABSTRACT
PURPOSE: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. METHODS: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. RESULTS: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/µmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).
Subject(s)
Glutamate Carboxypeptidase II , Positron-Emission Tomography , Humans , Male , Mice , Animals , Tissue Distribution , Cell Line, Tumor , Glutamate Carboxypeptidase II/metabolism , Positron-Emission Tomography/methods , Radioactive Tracers , Gallium Radioisotopes/pharmacokinetics , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/radiotherapy , Antigens, Surface/metabolism , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Radiochemistry , Dipeptides/pharmacokinetics , Dipeptides/chemistry , Heterocyclic Compounds, 1-Ring/chemistry , Heterocyclic Compounds, 1-Ring/pharmacokinetics , Positron Emission Tomography Computed Tomography/methodsABSTRACT
Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.
Subject(s)
Disinfectants , Disinfection , Disinfection/methods , Extracellular Polymeric Substance Matrix , Disinfectants/pharmacology , Chlorine/pharmacology , KineticsABSTRACT
Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.
Subject(s)
Carbon , Denitrification , Machine Learning , Wastewater/chemistry , Nitrogen , Waste Disposal, Fluid/methods , Sewage/microbiologyABSTRACT
Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02. The results show that [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [68Ga]Ga-ES-02 demonstrated higher binding affinity (Kd = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [68Ga]Ga-ES-02 (SUV15min max = 0.87 ± 0.03; SUV30min max = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 68Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [68Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [68Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.
ABSTRACT
OBJECTIVE: To explore the effect of ubiquitin-specific protease 42 (USP42) on osteogenic differentiation of human adipose-derived stem cells (hASCs) in vivo and in vitro. METHODS: A combination of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy. Alkaline phosphatase (ALP) staining and quantification, alizarin red S (ARS) staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group (knockdown group and overexpression group) and the control group. Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of osteogenesis related genes in the experimental group and control group, and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group. Nude mice ectopic implantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo. RESULTS: The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group, and those in overexpression group were significantly higher than those in control group. After 7 days of osteogenic induction, the ALP activity in the knockdown group was significantly higher than that in the control group, and ALP activity in overexpression group was significantly lower than that in control group. After 14 days of osteogenic induction, ARS staining was significantly deeper in the knockdown group than in the control group, and significantly lighter in overexpression group than in the control group. The results of qRT-PCR showed that the mRNA expression levels of ALP, osterix (OSX) and collagen type â (COLâ ) in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction, and those in overexpression group were significantly lower than those in control group. The results of Western blotting showed that the expression levels of runt-related transcription factor 2 (RUNX2), OSX and COLâ in the knockout group were significantly higher than those in the control group at 14 days after osteogenic induction, while the expression levels of RUNX2, OSX and COLâ in the overexpression group were significantly lower than those in the control group. Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group. CONCLUSION: Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vivo, and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs, and USP42 can provide a potential therapeutic target for bone tissue engineering.
Subject(s)
Core Binding Factor Alpha 1 Subunit , Osteogenesis , Thiolester Hydrolases , Animals , Humans , Mice , Adipose Tissue/cytology , Cell Differentiation/genetics , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/metabolism , Mice, Nude , Osteogenesis/genetics , RNA, Messenger/metabolism , Stem Cells/metabolism , Ubiquitin-Specific Proteases/genetics , Thiolester Hydrolases/metabolismABSTRACT
This study was conducted to investigate the effect and mechanism of phellopterin on colitis-associated cancer (CAC). For this purpose, CAC mouse model was established by AOM/DSS method, and the therapeutic effects of phellopterin in different doses were compared. The levels of interleukin-6 (IL-6), IL-1ß, IL-10, and tumor necrosis factor-α (TNF-α) in peripheral blood were detected by ELISA. The changes in T lymphocyte subsets and the expressions of CD163, CD206, Arg-1, and Ym-1 in colonic macrophages were detected. The expression of TLR4 and NF-κB p65 in the colon was tested by Western blot. Results showed that as against the Model group, the body weight and survival rate of mice treated with phellopterin were increased, the disease activity index, hematochezia rate, and tumor formation rate were decreased, the colon length was increased, and the number of tumors and spleen index were decreased (P<0.05). As against the Model group, the proportion of CD4+ and CD8+ in the peripheral blood of phellopterin intervention mice increased, the content of IL-6, IL-1ß, and TNF-α decreased, and the content of IL-10 increased. The expression of CD163, CD206, Arg-1, and Ym-1 in colonic macrophages was decreased. The protein expressions of TLR4 and NF-κB p65 in colon tissue were decreased (P<0.05). The effect of phellopterin intervention on CAC was dose-dependent. In conclusion, phellopterin can improve the symptoms and inflammatory response of CAC and inhibit the occurrence of colon cancer (CC) by inhibiting M2 polarization of macrophages and activation of the TLR4/NF-κB pathway.
Subject(s)
Colitis-Associated Neoplasms , Coumarins , Doxorubicin , NF-kappa B , Animals , Mice , Doxorubicin/analogs & derivatives , Interleukin-10 , Interleukin-6/metabolism , NF-kappa B/metabolism , Signal Transduction , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.
Subject(s)
Cognitive Dysfunction , Neoplasms , Humans , Neoplasms/therapy , Mental Fatigue , Disease ProgressionABSTRACT
Colon cancer (CC) is a common malignancy over the world and its morbidity and mortality significantly went up in China in recent years. Molecular functions in cancers have gradually been the pivot subject in cancer research. Neuroepithelial cell transforming 1 (NET1) was reported to contribute to prostate cancer and gastric cancer. Our study figured out that NET1 was overexpressed in CC cells. Then, loss-of-function assays revealed that NET1 facilitated CC cell proliferation and repressed CC cell apoptosis. Next, miR-338-3p was confirmed to target NET1. After that, we verified that circ_0017552 which originates from NET1 could positively modulate NET1 expression. Besides, circ_0017552 was a sponge of miR-338-3p. Rescue assays' results demonstrated that circ_0017552 could regulate CC cell proliferation and apoptosis through up-regulation of NET1. A transcription factor named Sp1 (SP1) was found to be present in circ_0017552. SP1 induced transcription of circ_0017552 to facilitate CC cell proliferation and inhibit CC cell apoptosis. In a word, SP1-induced circ_0017552 regulated CC cell proliferation and apoptosis through miR-338-3p/NET1 axis.
ABSTRACT
Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new 68Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Four radiotracers were synthesized with radiochemical purity >95 %, and exhibited high stability in vivo and in vitro. The inhibition constants (Ki) of SDTWS01-04 to PSMA were in the nanomolar range (<10 nM). Micro PET/CT imaging and biodistribution analysis revealed that 68Ga-SDTWS01 enabled clear tumor visualization in PET images at 1.5 h post-injection, with excellent pharmacokinetic properties. Notably, the kidney uptake of 68Ga-SDTWS01 significantly reduced, with higher tumor-to-kidney ratio (0.36 ± 0.02), tumor-to-muscle ratio (24.31 ± 2.10), compared with 68Ga-PSMA-11 (T/K: 0.15 ± 0.01; T/M: 14.97 ± 1.40), suggesting that 68Ga-SDTWS01 is a promising radiotracer for the diagnosis of PCa. Moreover, SDTWS01 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for the treatment of PCa.
Subject(s)
Gallium Radioisotopes , Glutamate Carboxypeptidase II , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Gallium Radioisotopes/chemistry , Humans , Male , Animals , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Glutamate Carboxypeptidase II/metabolism , Glutamate Carboxypeptidase II/antagonists & inhibitors , Tissue Distribution , Mice , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacology , Antigens, Surface/metabolism , Molecular Structure , Cell Line, TumorABSTRACT
Phenolic root exudates (PREs) secreted by wetland plants facilitate the accumulation of iron in the rhizosphere, potentially providing the essential active iron required for the generation of enzymes that degrade polycyclic aromatic hydrocarbon, thereby enhancing their biodegradation. However, the underlying mechanisms involved are yet to be elucidated. This study focuses on phenanthrene (PHE), a typical polycyclic aromatic hydrocarbon pollutant, utilizing representative PREs from wetland plants, including p-hydroxybenzoic, p-coumaric, caffeic, and ferulic acids. Using hydroponic experiments, 16S rRNA sequencing, and multiple characterization techniques, we aimed to elucidate the interaction mechanism between the accelerated degradation of PHE and the formation of rhizosphere biofilm/iron plaque influenced by PREs. Although all four types of PREs altered the biofilm composition and promoted the formation of iron plaque on the root surface, only caffeic acid, possessing a similar structure to the intermediate metabolite of PHE (catechol), could accelerate the PHE degradation rate. Caffeic acid, notable for its catechol structure, plays a significant role in enhancing PHE degradation through two main mechanisms: (a) it directly boosts PHE co-metabolism by fostering the growth of PHE-degrading bacteria, specifically Burkholderiaceae, and by facilitating the production of the key metabolic enzyme catechol 1,2-dioxygenase (C12O) and (b) it indirectly supports PHE biodegradation by promoting iron plaque formation on root surfaces, thereby enriching free iron for efficient microbial synthesis of C12O, a crucial factor in PHE decomposition.
Subject(s)
Biodegradation, Environmental , Biofilms , Iron , Phenanthrenes , Plant Roots , Rhizosphere , Phenanthrenes/metabolism , Iron/metabolism , Phenols/metabolism , WetlandsABSTRACT
Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.
Subject(s)
Alkaloids , Corydalis , Metabolomics , Plant Roots , Corydalis/genetics , Corydalis/metabolism , Metabolomics/methods , Plant Roots/metabolism , Plant Roots/genetics , Alkaloids/biosynthesis , Alkaloids/metabolism , Transcriptome , Benzylisoquinolines/metabolism , Gene Expression Regulation, Plant , Biosynthetic Pathways/genetics , Gene Expression Profiling , Berberine Alkaloids/metabolism , MetabolomeABSTRACT
Background: Epidemiological reports indicate a potential association between androgenic alopecia (AGA) and increased prostate cancer (PC) prevalence, but conflicting reports also exist. This study aims to elucidate the causality of AGA on PC risk using Mendelian randomization (MR) analysis. Materials and methods: Two-sample MR analyses utilized public genome-wide association studies summary data for single-nucleotide polymorphisms associated with AGA. Four statistical methods were used: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, with IVW as the preliminary estimation method. Additionally, sensitivity analyses were conducted to address pleiotropic bias. Results: Genetically proxied AGA did not demonstrate a causal effect on PC risk (IVW P > 0.05). Consistently, complementary methods yielded results aligned with IVW. Conclusions: Our MR analysis indicates no causal relationship between genetically predicted AGA and PC risk, suggesting that observed associations in epidemiological studies may not be causal.
ABSTRACT
Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.
Subject(s)
Homeostasis , Minocycline , Mitochondria , Reactive Oxygen Species , Retinitis Pigmentosa , Minocycline/pharmacology , Minocycline/therapeutic use , Animals , Retinitis Pigmentosa/drug therapy , Retinitis Pigmentosa/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Homeostasis/drug effects , Mice , Reactive Oxygen Species/metabolism , Retinal Degeneration/drug therapy , Retinal Degeneration/pathology , Retinal Degeneration/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/pathology , Photoreceptor Cells, Vertebrate/metabolism , Membrane Potential, Mitochondrial/drug effects , Microglia/drug effects , Microglia/metabolism , Retina/drug effects , Retina/pathology , Retina/metabolism , Humans , Antioxidants/pharmacology , Antioxidants/therapeutic useABSTRACT
The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.
ABSTRACT
Metal-nitrogen-carbon catalysts with hierarchically dispersed porosity are deemed as efficient geometry for oxygen reduction reaction (ORR). However, catalytic performance determined by individual and interacting sites originating from structural heterogeneity is particularly elusive and yet remains to be understood. Here, an efficient hierarchically porous Fe single atom catalyst (Fe SAs-HP) is prepared with Fe atoms densely resided at micropores and mesopores. Fe SAs-HP exhibits robust ORR performance with half-wave potential of 0.94 V and turnover frequency of 5.99 e-1s-1site-1 at 0.80 V. Theoretical simulations unravel a structural heterogeneity induced optimization, where mesoporous Fe-N4 acts as real active centers as a result of long-range electron regulation by adjacent microporous sites, facilitating O2 activation and desorption of key intermediate *OH. Multilevel operando characterization results identify active Fe sites undergo a dynamic evolution from basic Fe-N4 to active Fe-N3 under working conditions. Our findings reveal the structural origin of enhanced intrinsic activity for hierarchically porous Fe-N4 sites.
ABSTRACT
Objective: To explore the construction and application in the practice of green channel in No. 971 Naval Hospital of PLA (No. 971 Hospital mode) for the treatment of acute ischemic stroke (AIS). Methods: This retrospective study involved a cohort of 694 suspected stroke patients from December 2022 to November 2023 undergoing emergency treatment for stroke at our institution. Among them, 483 patients were treated with standard green channel (the control group), and 211 patients adopted the No. 971 Hospital mode for treatment (the study group). The biggest difference between the two groups was that the treatment process started before admission. We compared the effectiveness of the emergency treatment between the two groups and the thrombolysis treatment. Results: Compared with control group, the accuracy rate of determining stroke and the rate of thrombolysis were significantly higher (p = 0.002, 0.039) and the door to doctor arrival time (DAT) and the door to CT scan time (DCT) of the study group was significantly shorter (all p < 0.001). There were 49 patients (10.1%) and 33 patients (15.6%) from the control group and study group receiving thrombolysis, respectively. The DAT, DCT, imaging to needle time (INT), and door to needle time (DNT) of patients receiving thrombolysis in the study group were significantly shorter than that in the control group (all p < 0.01). The NIHSS in the study group after the thrombolysis was lower than that in the control group (p = 0.042). Conclusion: No. 971 Hospital model can effectively shorten DAT, DCT, INT, and DNT, and improve the effectiveness of thrombolysis and prognoses of AIS patients.
ABSTRACT
Harvesting fog is a potential and effective way to alleviate the crisis of water resource shortage. A highly efficient and economical fog harvesting method has always been a global and common goal. Here, a promising fog harvesting method by coupling plasma and micro/nano materials is proposed, which can achieve 93% fog collection efficiency with consuming power of only 0.76 W/0.04 m2. The basic method is to utilize nanoparticles to decorate both the discharge electrode and the collecting electrode of the micro/nano electrostatic fog collector. For the discharge electrode, the nanoparticles can achieve an order of magnitude higher electric field strength and a 28.6% decrease in the operating voltage (14 kV decreases to 10 kV). For the collecting electrode, a novel composite structure of hydrophobic/hydrophilic (HB/HL) is proposed. The core advantage is the directional droplet transport at the junction of HB and HL caused by surface tension can adjust the accumulated droplets on the two sides, which avoids the droplet residue and mesh blockage in the general structure. This technology provides an innovative approach for the collection of microdroplets and a new design idea for the fog collector to deal with the water crisis.
ABSTRACT
The myostatin (MSTN) gene exhibits significant nucleotide sequence variations in sheep, impacting growth characteristics and muscular traits of the body. However, its influence on specific growth traits in some sheep remains to be further elucidated. This study utilized single nucleotide polymorphism sequence analysis to investigate the role of the MSTN gene in meat production performance across four sheep breeds: Charolais sheep, Australian White sheep, crossbreeds of Australian White and Small-tailed Han, and crossbreeds of Charolais and Small-tailed Han. At a SNP locus of the MSTN gene, the C2361T site was identified, with three genotypes detected: CC, CT, and TT, among which CC predominated. Gene substitution effect analysis revealed that replacing C with T could elevate the phenotypic value. Comparative analysis of data from different genotypes within the same breed highlighted the superiority of CC and TT genotypes in phenotypic values, underscoring the significance of specific genotypes in influencing key traits. Contrasting the performance of different genotypes across breeds, Charolais sheep and Charolais Han hybrids demonstrated superiority across multiple indicators, offering valuable insights for breeding new sheep varieties. Analysis of gender effects on growth characteristics indicated that ewes exhibited significantly wider chest, waist, and hip widths compared to rams, while rams displayed better skeletal growth and muscle development. Additionally, the MSTN gene also exerted certain effects on lamb growth characteristics, with the CC genotype closely associated with weight. These findings not only contribute crucial insights for sheep breeding but also pave the way for future research exploring the interaction of this gene with others.