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Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.
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This research aims to investigate the causal effects of consumers' Covid-19 pandemic experiences on their preferences for sustainable consumption. Drawing on social identity theory, we argue that pandemic experiences heighten consumers' awareness of the importance of adhering to collective social norms, subsequently motivating them to adopt sustainable consumption practices that promote collective interests. Through three preregistered experiments, we demonstrate that: (i) Covid-19 pandemic experiences increase consumers' preferences for sustainable consumption; (ii) this effect is more pronounced for individuals with severer pandemic experiences and females; (iii) pandemic experiences influence sustainable consumption preferences by enhancing consumers' social normative compliance. This study contributes to the understanding of Covid-19's consequences from a micro-level perspective of consumer behavior and offers insights into the factors driving consumers' sustainable consumption preferences.
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COVID-19 , Comportamento do Consumidor , Normas Sociais , Humanos , COVID-19/psicologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Feminino , Masculino , Adulto , SARS-CoV-2 , Pessoa de Meia-Idade , Pandemias , Adulto Jovem , Identificação SocialRESUMO
Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.
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Complicações do Diabetes , Diabetes Mellitus , Exossomos , Células-Tronco Mesenquimais , Humanos , Exossomos/metabolismo , Complicações do Diabetes/metabolismo , Comunicação Celular , Células-Tronco Mesenquimais/metabolismo , Resultado do Tratamento , Diabetes Mellitus/metabolismoRESUMO
Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.
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Proteínas Adaptadoras de Transdução de Sinal , Diferenciação Celular , Condrócitos , Consolidação da Fratura , Osteogênese , Células-Tronco , Canais de Cátion TRPP , Animais , Consolidação da Fratura/fisiologia , Camundongos , Canais de Cátion TRPP/metabolismo , Canais de Cátion TRPP/genética , Condrócitos/metabolismo , Células-Tronco/metabolismo , Osteogênese/fisiologia , Camundongos Knockout , Condrogênese/fisiologia , Periósteo/metabolismo , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Modelos Animais de Doenças , MasculinoRESUMO
Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized with divinylbenzene (DVB) onto the surface of monodisperse magnetic nanoparticles (denoted as MNs@SiO2T-DvbDam). The magnetic polymer hybrid demonstrated high selectivity and capacity for AAs, which was mainly attributed to (1) electrostatic interactions from the cationic or basic moiety of DMAPAm and (2) the hydrophobic and π-π stacking interactions from the aromatic ring of DVB. Additionally, the surface of the hybrid exhibited amphiphilic property according to the ionization of DMAPAm, thus improving the compatibility of the adsorbent with the aqueous sample matrix. This strategy was proven to be robust in the analysis of real drug samples, which was characterized by a good linearity, high recovery and satisfactory reusability. This work confirmed that the proposed tool could be a promising candidate for enhancing the extraction selectivity of AAs in Traditional Chinese medicines (TCM).
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Ácidos Aristolóquicos , Nanocompostos , Acrilamida , Polímeros , Fenômenos MagnéticosRESUMO
PURPOSE: Nutrition intake is one of the modifiable risk factors for cognitive decline. Whether energy and protein intakes alter the association between pulmonary function (PF) and cognition has not been studied. METHODS: We made use of information from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2012. PF measures, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), were calculated, whereas cognitive function was assessed through four tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Energy and protein intakes were measured using the 24-h dietary recall method. Weighted generalized linear regression was performed upon adjustment for covariates. Further interaction analyses were conducted to investigate the effect of energy and protein intakes on the association between PF and cognition. RESULTS: We finally included 803 participants aged ≥ 60 years (54.4% female, weighted value). After adjusting for covariates, multiple measures (including FEV1, FVC, PEF, and composite PF) were all positively associated with better global cognition and the DSST score (P < 0.05). A stronger positive association between the DSST score and FEV1 (P for interaction = 0.001), FVC (P for interaction = 0.004), PEF (P for interaction = 0.003), and composite PF (P for interaction = 0.001) in lower energy intake. Similar results were observed in lower protein intake (all P for interaction < 0.05). CONCLUSION: Higher PF was independently associated with improved specific components of cognitive function (i.e., the DSST score). The positive association between PF and the DSST score was stronger in individuals with lower energy and protein intakes.
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Cognição , Pulmão , Idoso , Animais , Humanos , Feminino , Estados Unidos/epidemiologia , Masculino , Inquéritos Nutricionais , Capacidade Vital , Volume Expiratório ForçadoRESUMO
Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.
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Calosidades , Fraturas Ósseas , Idoso , Humanos , Animais , Camundongos , Consolidação da Fratura , Senescência Celular , Envelhecimento , Macrófagos , Células-TroncoRESUMO
Osteoarthritis is a degenerative disease characterized by abnormal neurovascularization at the osteochondral junctions, the regulatory mechanisms of which remain poorly understood. In the present study, a murine osteoarthritic model with augmented neurovascularization at the osteochondral junction is used to examine this under-evaluated facet of degenerative joint dysfunction. Increased extracellular RNA (exRNA) content is identified in neurovascularized osteoarthritic joints. It is found that the amount of exRNA is positively correlated with the extent of neurovascularization and the expression of vascular endothelial growth factor (VEGF). In vitro binding assay and molecular docking demonstrate that synthetic RNAs bind to VEGF via electrostatic interactions. The RNA-VEGF complex promotes the migration and function of endothelial progenitor cells and trigeminal ganglion cells. The use of VEGF and VEGFR2 inhibitors significantly inhibits the amplification of the RNA-VEGF complex. Disruption of the RNA-VEGF complex by RNase and polyethyleneimine reduces its in vitro activities, as well as prevents excessive neurovascularization and osteochondral deterioration in vivo. The results of the present study suggest that exRNAs may be potential targets for regulating nerve and blood vessel ingrowth under physiological and pathological joint conditions.
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Osteoartrite , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Simulação de Acoplamento Molecular , Osteoartrite/metabolismo , RNA/genéticaRESUMO
Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y-box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis-splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age-related osteoporosis.
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Células-Tronco Mesenquimais , Osteoporose , Humanos , Camundongos , Animais , Osteogênese/genética , Envelhecimento/metabolismo , Senescência Celular , Diferenciação Celular/genética , Osteoporose/metabolismo , Células da Medula Óssea , Proteína 1 de Ligação a Y-Box/metabolismoRESUMO
Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
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Células-Tronco Mesenquimais , Osteogênese , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Lipólise , Linfopoese , Células-Tronco Mesenquimais/metabolismo , CamundongosRESUMO
Cerebral ischemia could induce depressive-like behaviors; however, the alteration of gamma-aminobutyric acid receptors type B (GABAB) receptors in these pathological processes has not been extensively investigated. The aim of the current study was to document the behavioral change and the alteration of GABAB receptors in chronic cerebral hypoperfusion. The permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) was performed to induce chronic cerebral ischemia (CCH). The depressive-like behaviors were evaluated with sucrose preference test, novelty suppress feeding test as well as forced swim test at 4, 8, and 12 weeks after the 2VO surgery. The total, surface and intracellular expressions of GABAB subunit 1 (GABAB1) and subunit 2 (GABAB2) in hippocampal CA1 were quantified by western blot. The depressive-like behaviors were observed in rats suffered from 4, 8, and 12 weeks 2VO in sucrose preference test, novelty suppress feeding test and forced swim test. In addition, the surface and total expression of GABAB1 in CA1 was reduced at 4 weeks after 2VO rather than 8 or 12 weeks. While the surface and total expression of GABAB2 in CA1 was decreased throughout the ischemia timeline (4, 8, and 12 weeks). Taken together, our findings suggested the potential roles of GABAB1 and GABAB2 subunits involved in depressive-like behaviors caused by chronic cerebral hypoperfusion.
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Isquemia Encefálica , Região CA1 Hipocampal , Animais , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Região CA1 Hipocampal/metabolismo , Hipocampo/metabolismo , Ratos , Ratos Sprague-Dawley , Sacarose/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin ß3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.
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MicroRNAs , Osteogênese , Envelhecimento/genética , Animais , Células Endoteliais/metabolismo , Endotélio , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica , Osteogênese/genéticaRESUMO
Mucosal healing is a key treatment goal for inflammatory bowel disease, and adequate epithelial regeneration is required for an intact gut epithelium. However, the underlying mechanism for mucosal healing is unclear. Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of inflammatory bowel disease. Here, we report that a lncRNA named Gm31629 decreased in intestinal epithelial cells in response to inflammatory stimulation. Gm31629 deficiency led to exacerbated intestinal inflammation and delayed epithelial regeneration in dextran sulfate sodium-induced (DSS-induced) colitis model. Mechanistically, Gm31629 promoted E2F pathways and cell proliferation by stabilizing Y-box protein 1 (YB-1), thus facilitating epithelial regeneration. Genetic overexpression of Gm31629 protected against DSS-induced colitis in vivo. Theaflavin 3-gallate, a natural compound mimicking Gm31629, alleviated DSS-induced epithelial inflammation and mucosal damage. These results demonstrate an essential role of lncRNA Gm31629 in linking intestinal inflammation and epithelial cell proliferation, providing a potential therapeutic approach to inflammatory bowel disease.
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Colite , Doenças Inflamatórias Intestinais , RNA Longo não Codificante , Animais , Colite/induzido quimicamente , Colite/genética , Colite/prevenção & controle , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Inflamação/genética , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis.
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Células-Tronco Mesenquimais , Adipogenia , Envelhecimento , Animais , Medula Óssea , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese , RatosRESUMO
BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71â¢75% for adenovirus, 58â¢76% for norovirus, 53â¢50% for rotavirus A, and 72â¢07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66â¢53% and 90â¢48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.
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Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.
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Autofagia , Remodelação Óssea , Osso e Ossos/patologia , Osteíte Deformante/patologia , Osteoartrite/patologia , Osteoporose/patologia , Animais , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Homeostase , Humanos , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/metabolismo , Osteíte Deformante/fisiopatologia , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/fisiopatologiaRESUMO
Obesity is characterized by the expansion of adipose tissue which is partially modulated by adipogenesis. In the present study, we identified five differentially expressed genes by incorporating two adipogenesis-related datasets from the GEO database and their correlation with adipogenic markers. However, the role of scavenger receptor class A member 3 (SCARA3) in obesity-related disorders has been rarely reported. We found that Scara3 expression in old adipose tissue-derived mesenchymal stem cells (Ad-MSCs) was lower than it in young Ad-MSCs. Obese mice caused by deletion of the leptin receptor gene (db/db) or by a high-fat diet both showed reduced Scara3 expression in inguinal white adipose tissue. Moreover, hypermethylation of SCARA3 was observed in patients with type 2 diabetes and atherosclerosis. Data from the CTD database indicated that SCARA3 is a potential target for metabolic diseases. Mechanistically, JUN was predicted as a transcriptional factor of SCARA3 in different databases which is consistent with our further bioinformatics analysis. Collectively, our study suggested that SCARA3 is potentially associated with age-related metabolic dysfunction, which provided new insights into the pathogenesis and treatment of obesity as well as other obesity-associated metabolic complications.
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Tecido Adiposo Branco/metabolismo , Aterosclerose/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Choque Térmico/metabolismo , Obesidade/metabolismo , Receptores Depuradores Classe A/metabolismo , Adipogenia/fisiologia , Animais , Aterosclerose/genética , Metilação de DNA , Bases de Dados Genéticas , Diabetes Mellitus Tipo 2/genética , Dieta Hiperlipídica , Redes Reguladoras de Genes , Proteínas de Choque Térmico/genética , Humanos , Masculino , Camundongos , Obesidade/genética , Receptores para Leptina/genética , Receptores Depuradores Classe A/genéticaRESUMO
Picophytoplankton (<3 µm), comprising picocyanobacteria (PCY) and photosynthetic picoeukaryotes (PPEs), are considerably important in the material circulation and energy flow of aquatic ecosystems. To explore the temporal and spatial variation patterns of picophytoplankton and their correlations with environmental factors in lotic Yangtze-connected lakes, field in-situ investigations were performed on a monthly basis during the wet season (May to August) in 2019 in East Lake Dongting, a Yangtze-connected lake. The results indicated that both the Chla biomass and abundances of picophytoplankton exhibited significant spatial and temporal variability (P<0.05). The picophytoplankton Chla biomass showed an average concentration of 8.52 µg·L-1 and accounted for 41.6% to total phytoplankton on an average. From May to August, Chla biomass of picophytoplankton kept increasing with increasing temperature, especially in the north and south of the lake, and it was the lowest in the east of the lake. PCY dominated picophytoplankton abundance in East Lake Dongting and was 3.4 times the abundance of PPEs on an average. Similar spatial and temporal variation patterns were observed between PCY and PPEs. The abundances of PCY and PPEs both increased first and then decreased during the wet season. Spatially, picophytoplankton showed a trend to migrate from the northern lake to the southern lake from May to July, and the abundance significantly declined in August and peaked mainly in the north of the lake. The analysis results showed that picophytoplankton in East Lake Dongting exhibited significant spatial and temporal variability during the wet season; the water level and Nï¼P ratio were determined to be the most important factors explaining the variation of the abundance proportion of PCY and PPEs.
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Ecossistema , Lagos , China , Monitoramento Ambiental , Fotossíntese , Fitoplâncton , Estações do AnoRESUMO
In the central nervous system, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential to maintain normal neuronal function. Recent studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury, but the mechanisms remain unclear. Autophagy is activated in cerebral ischemia, but its role in cell death/survival remains controversial. In this study, our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion (OGD/R) in hippocampal HT22 neurons. Furthermore, in the OGD/R group, p-mTOR, p-ULK1 (Ser757), and p62 were significantly decreased, while p-ULK1 (Ser317), atg5, and beclin1 were remarkably increased. ZD7288 did not change the expression of p-ULK1 (Ser757), ULK1 (Ser317), p62, Beclin1, and atg5, which are involved in regulating autophagosome formation. Besides, we found that OGD/R induced a significant increase in Cathepsin D expression, but not LAMP-1. Treatment with ZD7288 at 10 µmol/L in the OGD/R group did not change the expression of cathepsin D and LAMP-1. However, chloroquine (CQ), which decreases autophagosome-lysosome fusion, eliminated the correction of excessive autophagy and neuroprotection by ZD7288. Besides, shRNA knockdown of HCN2 channels significantly reduced the accumulation of LC3-II and increased neuron survival in the OGD/R and transient global cerebral ischemia (TGCI) models, and CQ also eliminated the effects of HCN2-shRNA. Furthermore, we found that the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes decreased in Con-shRNA-transfected HT22 neurons exposed to OGD/R or CQ. In HCN2-shRNA-transfected HT22 neurons, the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes increased under OGD/R; however, the percentage was significantly decreased by the addition of CQ to HCN2-shRNA-transfected HT22 neurons. The present results demonstrated that blockade of HCN2 channels provides neuroprotection against OGD/R and TGCI by accelerating autophagic degradation attributable to the promotion of autophagosome and lysosome fusion.