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1.
PLoS Biol ; 22(8): e3002753, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39163396

RESUMO

Cell-to-cell mitochondrial transfer has recently been shown to play a role in maintaining physiological functions of cell. We previously illustrated that mitochondrial transfer within osteocyte dendritic network regulates bone tissue homeostasis. However, the mechanism of triggering this process has not been explored. Here, we showed that stressed osteocytes in mice release adenosine diphosphate (ADP), resulting in triggering mitochondrial transfer from healthy osteocytes to restore the oxygen consumption rate (OCR) and to alleviate reactive oxygen species accumulation. Furthermore, we identified that P2Y2 and P2Y6 transduced the ADP signal to regulate osteocyte mitochondrial transfer. We showed that mitochondrial metabolism is impaired in aged osteocytes, and there were more extracellular nucleotides release into the matrix in aged cortical bone due to compromised membrane integrity. Conditioned medium from aged osteocytes triggered mitochondrial transfer between osteocytes to enhance the energy metabolism. Together, using osteocyte as an example, this study showed new insights into how extracellular ADP triggers healthy cells to rescue energy metabolism crisis in stressed cells via mitochondrial transfer in tissue homeostasis.


Assuntos
Difosfato de Adenosina , Homeostase , Mitocôndrias , Osteócitos , Animais , Osteócitos/metabolismo , Mitocôndrias/metabolismo , Camundongos , Difosfato de Adenosina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Consumo de Oxigênio , Metabolismo Energético , Camundongos Endogâmicos C57BL , Estresse Fisiológico
2.
Proc Natl Acad Sci U S A ; 121(35): e2320804121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39172790

RESUMO

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance.


Assuntos
Proteína BRCA1 , Reparo do DNA , Chaperonas de Histonas , Histona-Lisina N-Metiltransferase , Animais , Humanos , Camundongos , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Linhagem Celular Tumoral , Cromatina/metabolismo , Quebras de DNA de Cadeia Dupla , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Chaperonas de Histonas/metabolismo , Chaperonas de Histonas/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Metilação , Metiltransferases/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Tolerância a Radiação/genética
3.
Psychophysiology ; : e14675, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218953

RESUMO

Peer presence influences risk-taking behavior, particularly in adolescence. Based on the dual system model, this event-related potential study examined whether and how the presence of a peer displayed a preference for risky behavior would increase adolescents' risk-taking by disrupting their cognitive control processes in either emotional or non-emotional contexts. A sample of 106 adolescents (17-19 years of age) completed two Stoop tasks and a Balloon Analog Risk Task under three peer presence conditions. Results revealed that compared to other conditions, the presence of a risk-averse peer caused adolescents to make safer decisions through improving their conflict monitoring (more negative N200-diff), whereas a risk-preference peer's presence led adolescents to more risky decisions through disrupting their conflict resolution (more positive N450-diff) but they were only observed on the Emotional Stroop task. These findings suggest that different peer presence contexts could increase or decrease adolescents' risk-taking behaviors by influencing their cognitive control under an emotional context rather than in a non-emotional context.

4.
BMC Musculoskelet Disord ; 25(1): 697, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223520

RESUMO

OBJECTIVE: There is currently a lack of in-depth comparative evaluation regarding the biomechanical properties of novel intramedullary nail devices in the treatment of basal femoral neck fractures (BFNF). This study aims to utilize finite element analysis to compare the performance differences of two novel devices with traditional PFNA and InterTan nails in the fixation of BFNF. METHODS: Based on a validated finite element model, this study constructed an accurate BFNF model and implanted four different intramedullary nail devices: PFNA, InterTan nail, PFBN (proximal femoral biomimetic nail), and NIS (novel intramedullary system). Under a vertical load of 2100N, the displacement and Von Mises stress (VMS) distribution of each group of models were evaluated through simulation testing. RESULTS: Under a load of 2100N, the PFBN device exhibited the best performance in terms of displacement and peak stress, while PFNA performed poorly. The peak displacement of the NIS device was lower than that of PFNA and InterTan nails, while the peak stress of the InterTan nail was lower than that of PFNA and NIS. CONCLUSION: The PFBN device demonstrates stronger load-bearing and shear-resistant properties in the treatment of BFNF, and the NIS device also shows significant improvement in stability. Therefore, both the PFBN and NIS devices are reliable internal fixation techniques for the treatment of CFIFs, with potential clinical application prospects.


Assuntos
Pinos Ortopédicos , Fraturas do Colo Femoral , Análise de Elementos Finitos , Fixação Intramedular de Fraturas , Humanos , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/fisiopatologia , Fenômenos Biomecânicos/fisiologia , Estresse Mecânico , Suporte de Carga
5.
J Youth Adolesc ; 51(11): 2161-2172, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35861907

RESUMO

A number of studies have focused on the same-sex peer effect on and the developmental difference in adolescent risk-taking in terms of the dual systems model. Little research, however, addresses the effects of different observers, the role of different levels of individual self-control, and their interactions. To fill this gap, the present study examined the main and interactive effects of observer presence and individual self-control on male adolescents' risk-taking behavior with an experimental design. A total of 261 male adolescents (Mage = 15.79 ± 0.79, range = 14-18) completed an adapted Stoplight Task, which measures risk-taking behavior, in the presence of an observer, either peer or adult, either male or female. The results indicated that a same-sex peer's presence and low self-control were both risk factors of male adolescents' risk-taking, but did only low self-control male adolescents take serious risks when in the presence of a same-sex peer whereas those with high self-control consistently had low levels of risk-taking under any condition. An opposite-sex observer, particularly an opposite-sex adult's presence, played a similar protective role for male adolescents with low self-control. The findings suggest that a high level of self-control closely related to the cognitive control system may significantly buffer the negative effect of an adverse social stimulus which activates the social-emotional system on male adolescents' risk-taking; the findings also reveal that an opposite-sex adult's presence may contribute to a decrease in male adolescents' risk-taking by improving their cognitive control system.


Assuntos
Comportamento do Adolescente , Autocontrole , Adolescente , Comportamento do Adolescente/psicologia , Adulto , Feminino , Humanos , Masculino , Grupo Associado , Assunção de Riscos , Comportamento Social
6.
Nanotechnology ; 32(49)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34428756

RESUMO

To address the flammable and chemical unstable problems of liquid electrolyte, the solid electrolyte is a promising candidate to replace liquid electrolyte for solid-state batteries. Herein, a composite polymer electrolyte (CPE) of 3D polyimide (PI)-nanofiber membrane-incorporated polyethylene oxide (PEO)/lithium bis (triflu-romethanesulphonyl) imid (LiTFSI) is reported. Three advantages of the PI nanofiber network in the CPE include providing a continuous, rapid transport channel of lithium ions to improve the Li-ion conductivity, improving the mechanical properties and stability, and effectively inhibiting the dendrite growth of Li metal. The PI/PEO/LiTFSI CPE delivers an ionic conductivity of 4.2 × 10-4S cm-1at 60 °C, a wider electrochemical window to 5.4 V, and an excellent thermal stability, which result in the excellent electrochemical performance of LiFePO4full cells assembled with PI/PEO/LiTFSI CPE.

7.
J Anim Physiol Anim Nutr (Berl) ; 105(6): 1063-1074, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33817860

RESUMO

This study aimed to investigate the protective effects and underlying mechanism of seaweed polysaccharide (SWP) on intestinal epithelial barrier dysfunction induced by E. coli in an IPEC-J2 model. A preliminary study was done to screen optimum SWP concentrations by cell viability, cytotoxicity, apoptosis and proliferation evaluation. The regular study was conducted to evaluate the protective effects of SWP against E. coli challenge via the analysis of transepithelial electrical resistance (TEER), tight junction proteins, NF-κB signalling pathway, proinflammatory cytokines and the E. coli adhesion and invasion. Our results show that 4 h E. coli challenge down-regulated tight junction proteins expression, decreased TEER, activated NF-κB signalling pathway and increased proinflammatory response, which indicates that the E. coli infection model was well-established. Pre-treatment with 240 µg/ml SWP for 24 h alleviated the 4 h E. coli -induced intestinal epithelial barrier dysfunction, as evidenced by the up-regulated expression of Occludin, Claudin-1 and ZO-1 at both mRNA and protein level and the increased TEER of IPEC-J2 cells. Pre-incubation with 240 µg/ml SWP for 24 h inhibited the activation of the NF-κB signalling pathway by 4 h E. coli challenge, including the decreased mRNA expression of TLR-4, MyD88, IκBα, p-65, as well as the reduced ratio of protein expression of p-p65/p65. Also, pre-treatment with 240 µg/ml SWP for 24 h decreased proinflammatory response (IL-6 and TNF-α) induced by 4 h E. coli challenge and decreased the E. coli adhesion and invasion. In conclusion, SWP mitigated intestinal barrier dysfunction caused by E. coli through NF-κB pathway in IPEC-J2 cells and 240 µg/ml SWP exhibited better effect. Our results also provide a fundamental basis for SWP in reducing post-weaning diarrhoea of weaned piglets, especially under E. coli -infected or in-feed antibiotic-free conditions.


Assuntos
Escherichia coli Enterotoxigênica , Alga Marinha , Animais , Linhagem Celular , Células Epiteliais , Mucosa Intestinal , NF-kappa B/genética , Polissacarídeos/farmacologia , Suínos
8.
J Anim Physiol Anim Nutr (Berl) ; 104(6): 1875-1883, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32227536

RESUMO

This study aimed to evaluate the effects of dietary guanidine acetic acid (GAA) supplementation on growth performance, carcass traits and the expression of muscle growth-related genes in finishing pigs. A total of 128 (81.03 ± 1.09 kg body weight) crossbred pigs (Duroc × Landrace ×Yorkshire) were blocked by body weight and allotted to 16 pens (eight pigs per pen), and pens were randomly assigned within blocks to one of five dietary treatments, with a basal diet (control group) or a basal diet supplemented with 0.03%, 0.06% and 0.09% GAA respectively. During the 60-day trial, GAA increased the average dairy gain (ADG) and average daily feed intake (ADFI) (p < .05). The back fat thickness of pigs fed 0.06% GAA was lower than other groups (p < .05). Pigs fed 0.06% GAA had improved lean meat percentage, loin muscle area, shear force and cross-sectional area of muscle fibre in comparison with control group (p < .05). The drop loss and the muscle fibre density in pigs fed 0.06% GAA were lower than control (p < .05). In addition, dietary GAA enhanced the expression of myosin heavy chain gene (MYH4), myogenic determination (Myod) and myogenic factor 5 (Myf5) in longissimus dorsi and carnitine palmitoyltransferase-1(CPT-1) in liver (p < .05). Meanwhile, GAA decreased the expression of Myostatin in longissimus dorsi and fatty acid synthase (FAS) in liver (p < .05). In conclusion, our results showed that appropriate dietary GAA supplementation (0.06%) promotes skeletal muscle development through changing myogenic gene expression and myofibre characteristics.


Assuntos
Ração Animal , Composição Corporal , Ração Animal/análise , Animais , Dieta/veterinária , Expressão Gênica , Glicina/análogos & derivados , Carne , Desenvolvimento Muscular , Músculo Esquelético , Suínos
9.
Brief Bioinform ; 14(4): 460-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22988254

RESUMO

Because of its widespread occurrence and role in shaping evolutionary processes in the biological kingdom, especially in plants, polyploidy has been increasingly studied from cytological to molecular levels. By inferring gene order, gene distances and gene homology, linkage mapping with molecular markers has proven powerful for investigating genome structure and organization. Here we review and assess a general statistical model for three-point linkage analysis in autotetraploids by integrating double reduction, a phenomenon that commonly occurs in autopolyploids whose chromosomes are derived from a single ancestral species. This model does not require any assumption on the distribution of the occurrence of double reduction and can handle the complexity of multilocus linkage in terms of crossover interference. Implemented with the expectation-maximization (EM) algorithms, the model can estimate and test the recombination fractions between less informative dominant markers, thus facilitating its practical implications for any autopolyploids in most of which inexpensive dominant markers are still used for their genetic and evolutionary studies. The model was applied to reanalyze a published data in tetraploid switchgrass, validating its practical usefulness and utilization.


Assuntos
Ligação Genética , Modelos Genéticos , Poliploidia , Mapeamento Cromossômico , Marcadores Genéticos , Modelos Estatísticos
10.
Appl Opt ; 53(16): 3556-64, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24922434

RESUMO

A dual-wedge scanner has potential applications in laser imaging radar. To realize fast scanning imaging without a blind region, the rotation rates of the wedges have to be controlled to perform beam scanning along appropriate track paths. The first-order paraxial approximation method is employed to investigate the 2D scan patterns and path density for different angular frequency ratios of the wedges rotating steadily in the same and opposite directions. The frame rate of no-blind-region scanning imaging is estimated in terms of the imaging coverage requirement. The internal relations between the rotation rates, the instantaneous field of view (IFOV), and the imaging velocity are revealed. The results show that the spiral scanning trace, resulting from co-rotating wedges, is dense in the center and sparse at the edge of the scanning field. The reverse results can be obtained for the rosette scanning trace, resulting from counter-rotating wedges. The denser the scanning trace is, the longer the scan period is. The faster the wedges rotate and the wider the IFOV is, the higher the frame rate is. When the ratio of the width of IFOV to the angular radius of the scanning field is 0.15, the frame rate of no-blind-region spiral scanning imaging can be up to 18 fps for wedge rotation rate of 12000 r/min, and that for rosette scanning imaging can be up to 20 fps.

11.
Appl Opt ; 53(25): 5775-83, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25321377

RESUMO

Based on the vector form Snell's law, ray tracing is performed to quantify the pointing errors of Risley-prism-based beam steering systems, induced by component errors, prism orientation errors, and assembly errors. Case examples are given to elucidate the pointing error distributions in the field of regard and evaluate the allowances of the error sources for a given pointing accuracy. It is found that the assembly errors of the second prism will result in more remarkable pointing errors in contrast with the first one. The pointing errors induced by prism tilt depend on the tilt direction. The allowances of bearing tilt and prism tilt are almost identical if the same pointing accuracy is planned. All conclusions can provide a theoretical foundation for practical works.

12.
J Orthop Surg Res ; 19(1): 583, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304891

RESUMO

OBJECTIVE: Given the recent application of two new types of intramedullary nail devices in the treatment of comminuted femoral intertrochanteric fractures (CFIFs), there is still a lack of deep understanding and comparative evaluation of their biomechanical properties. Therefore, this study aims to systematically compare the advantages and disadvantages of these two new devices with traditional proximal femoral nail antirotation (PFNA) and InterTan nails in the fixation of CFIFs through finite element analysis. METHODS: Based on the validated finite element model, this study constructed an accurate CFIFs model. In this model, PFNA, InterTan nails, proximal femoral bionic nails (PFBN), and new intramedullary systems (NIS) were implanted, totaling four groups of finite element models. Each group of models was subjected to simulation tests under a vertical load of 2100 N to evaluate the displacement and Von Mises stress (VMS) distribution of the femur and intramedullary nail devices. RESULTS: Under a vertical load of 2100 N, a comparative analysis of the four finite element models showed that the NIS device exhibited the most superior performance in terms of peak displacement, while the PFNA device performed relatively poorly. Although the NIS device had the highest peak stress in the femur, it had the smallest peak displacement of both the femur and intramedullary nail devices, and the peak stress was mainly concentrated on the lateral side of the femur, with significantly lower stress in the proximal femur compared to the other three intramedullary nail devices. In contrast, the PFBN device had the lowest peak stress in the femur, and its peak displacement of both the femur and intramedullary nail devices was also less than that of PFNA and InterTan nails. CONCLUSION: This study demonstrates that in the treatment of CFIFs, PFBN and NIS devices exhibit superior biomechanical performance compared to traditional PFNA and InterTan nail devices. Especially the NIS device, which can achieve good biomechanical results when fixing femoral intertrochanteric fractures with missing medial wall. Therefore, both PFBN and NIS devices can be considered reliable closed reduction and internal fixation techniques for the treatment of CFIFs, with potential clinical application value.


Assuntos
Pinos Ortopédicos , Análise de Elementos Finitos , Fixação Intramedular de Fraturas , Fraturas Cominutivas , Fraturas do Quadril , Humanos , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/instrumentação , Fenômenos Biomecânicos , Fraturas do Quadril/cirurgia , Fraturas Cominutivas/cirurgia , Fêmur/cirurgia
13.
Kaohsiung J Med Sci ; 40(7): 621-630, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820598

RESUMO

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/ß-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/ß-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed ß-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.


Assuntos
Fosfatos de Cálcio , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Impressão Tridimensional , Alicerces Teciduais , Ubiquitina-Proteína Ligases , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Alicerces Teciduais/química , Coelhos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Fosfatos de Cálcio/química , Diferenciação Celular , Engenharia Tecidual/métodos , Masculino , Regeneração Óssea/genética
14.
Medicine (Baltimore) ; 103(33): e39350, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151516

RESUMO

BACKGROUND: Previous researches have demonstrated that the traditional Chinese medicine could therapeutically treat inflammatory and hypoxic diseases by enhancing the functionality of mesenchymal stem cells. However, its mechanism was not yet clear. This research aimed to investigate the impact of the traditional Chinese medicine Sijunzi decoction and its herb monomer ginsenoside Rg1 on the proliferation and differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and explore the underlying mechanisms. METHODS: Different concentrations of Sijunzi decoction and Rg1 were applied to differentiating induced hUC-MSCs. The CCK-8 test was utilized to evaluate cell proliferation activity and identify suitable drug concentrations. Alizarin Red staining was employed to detect the formation of calcium nodules, and Oil Red O staining was used to assess the formation of lipid droplets. PCR was utilized to examine gene expression related to osteogenic differentiation, adipogenic differentiation, and the HIF-1α signaling pathway in hUC-MSCs. Western blot analysis was conducted to evaluate protein expression in osteogenic differentiation and HIF-1α. ELISA was performed to measure HIF-1α signaling factors and inflammatory cytokine expression. Biochemical assays were used to assess changes in oxidative stress indicators. RESULTS: The Sijunzi decoction and Rg1 both demonstrated a dose-dependent promotion of hUC-MSC proliferation. The Sijunzi decoction significantly increased the expression of genes and proteins relevant to osteogenesis, such as osterix, osteocalcin, RUNX2, and osteopontin, and activated the HIF-1α pathway in hUC-MSCs. (P < .05). Similar effects were observed at the gene level after treatment with Rg1. Simultaneously, Sijunzi decoction significantly reduced the secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, while increasing the secretion of the anti-inflammatory cytokine IL-10 during osteogenic differentiation (P < .05). Moreover, Sijunzi decoction lowered oxidative stress levels and enhanced the antioxidant capacity of hUC-MSCs during osteogenic differentiation (P < .05). However, the impact of Sijunzi decoction on hUC-MSCs toward adipogenic differentiation was not significant (P > .05). CONCLUSION: Sijunzi decoction promotes the proliferation and osteogenic differentiation of hUC-MSCs, potentially through the activation of the HIF-1α signaling pathway and by modulating the microenvironment via reducing inflammation and oxidative stress levels. Rg1 might be involved in this process.


Assuntos
Diferenciação Celular , Proliferação de Células , Medicamentos de Ervas Chinesas , Ginsenosídeos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células-Tronco Mesenquimais , Osteogênese , Cordão Umbilical , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Cordão Umbilical/citologia , Osteogênese/efeitos dos fármacos , Ginsenosídeos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Adipogenia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas
15.
Nat Commun ; 15(1): 5094, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877020

RESUMO

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.


Assuntos
Reabsorção Óssea , Ferroptose , Mitocôndrias , Células Mieloides , Osteoclastos , Osteoporose , Animais , Mitocôndrias/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osteoclastos/metabolismo , Células Mieloides/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Camundongos , Glucocorticoides/metabolismo , Glutationa/metabolismo , Camundongos Endogâmicos C57BL , Diferenciação Celular , Camundongos Knockout , Humanos , Masculino
16.
Sci Adv ; 10(26): eadk2913, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941455

RESUMO

The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.


Assuntos
Astrócitos , Barreira Hematoencefálica , Células Endoteliais , Mitocôndrias , Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Animais , Mitocôndrias/metabolismo , Camundongos , Células Endoteliais/metabolismo , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética
17.
Appl Opt ; 52(7): 1389-98, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23458790

RESUMO

Two different analytical methods, the first-order paraxial approximation method and the nonparaxial ray tracing method, are applied to determine the steering mechanism of the Risley prism system, including the pointing prediction and the complete and exact inverse orientation solutions. The analytical results obtained with the two different methods are investigated in detail about the pointing prediction and the two groups of inverse orientation solutions, respectively. Risley prism equipment for wide angular range beam scanning is assembled and the experimental setup is built to test the steering mechanism of the Risley prism system. Experimental results validate the availability of the nonparaxial ray tracing method to discuss the beam steering mechanism for the Risley prism system.

18.
Appl Opt ; 52(12): 2849-57, 2013 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-23669697

RESUMO

Two exact inverse solutions of Risley prisms have been given by previous authors, based on which we calculate the gradients of the scan field that open a way to investigate the nonlinear relationship between the slewing rate of the beam and the required angular velocities of the two wedge prisms in the Risley-prism-based beam steering system for target tracking. The limited regions and singularity point at the center and the edge of the field of regard are discussed. It is found that the maximum required rotational velocities of the two prisms for target tracking are nearly the same and are dependent on the altitude angle. The central limited region is almost independent of the prism parameters. The control singularity at the crossing center path can be avoided by switching the two solutions.

19.
Emerg Microbes Infect ; 12(2): 2231573, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37394992

RESUMO

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Camundongos , Animais , Humanos , Hemaglutininas , Vacinas contra COVID-19 , Vírus da Influenza A Subtipo H1N1/genética , Microscopia Crioeletrônica , Anticorpos Antivirais , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinas contra Influenza/genética , Anticorpos Neutralizantes , Glicoproteína da Espícula de Coronavírus/genética
20.
ACS Chem Neurosci ; 13(4): 454-463, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35114083

RESUMO

Alzheimer's disease (AD) is the most common type of dementia that occurs in the elderly. Amyloid hypothesis is one of the most studied pathological mechanisms, and ß-amyloid (Aß) is the drug target for most clinical trials. Mitochondrial dysfunction induced by the Aß-precursor protein (APP)/Aß has been suggested to play a key role in the development of AD. Here, we explored the effects of myricetin, a polyphenol compound abundant in fruits and vegetables, on mitochondrial damages in N2a-SW cells. After the treatment of myricetin, mitochondrial depolarization was improved by increasing the mitochondrial membrane potential. Mitochondrial biogenesis as well as mitochondrial genome integrity was enhanced via increased levels of PGC-1α, Nrf1, TFAM, and the copy number of mtDNA. Mitochondrial functions were restored as represented by the increased levels of proteins involved in the electron transport chain and the adenosine 5'-triphosphate (ATP) content and the decreased concentration of ROS. Mitochondrial dynamics and mitophagy were ameliorated through the regulation of proteins involved in fusion (OPA1 and Mfn2), fission (Drp1 and Fis1), and mitophagy (PINK1 and Parkin). Thus, it is summarized that myricetin could recover the mitochondrial impairments in N2a-SW cells, exhibiting the potential to promote neuroprotection for APP/Aß-related diseases, including AD.


Assuntos
Doença de Alzheimer , Flavonoides , Idoso , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Mitocôndrias/metabolismo , Mitofagia
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