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1.
JHEP Rep ; 6(4): 101019, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38455470

RESUMO

Background & Aims: Recent studies have implicated platelets, particularly α-granules, in the development of non-alcoholic steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet α-granules released during platelet activation. Hence, we aimed to determine the role of platelet-derived TSP1 in NASH. Methods: Platelet-specific Tsp1 knockout mice (TSP1Δpf4) and their wild-type littermates (TSP1F/F) were used. NASH was induced by feeding the mice with a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed. Results: Although TSP1 deletion in platelets did not affect diet-induced steatosis, TSP1Δpf4 mice exhibited attenuated NASH and liver fibrosis, accompanied by improvements in plasma glucose and lipid homeostasis. Furthermore, TSP1Δpf4 mice showed reduced intrahepatic platelet accumulation, activation, and chemokine production, correlating with decreased immune cell infiltration into the liver. Consequently, this diminished proinflammatory signaling in the liver, thereby mitigating the progression of NAFLD. Moreover, in vitro data revealed that co-culturing TSP1-deficient platelets in a human liver NASH organoid model attenuated hepatic stellate cell activation and NASH progression. Additionally, TSP1-deficient platelets play a role in regulating brown fat endocrine function, specifically affecting Nrg4 (neuregulin 4) production. Crosstalk between brown fat and the liver may also influence the progression of NAFLD. Conclusions: These data suggest that platelet α-granule-derived TSP1 is a significant contributor to diet-induced NASH and fibrosis, potentially serving as a new therapeutic target for this severe liver disease. Impact and implications: Recent studies have implicated platelets, specifically α-granules, in the development of non-alcoholic steatohepatitis, yet the precise mechanisms remain unknown. In this study, through the utilization of a tissue-specific knockout mouse model and human 3D liver organoid, we demonstrated that platelet α-granule-derived TSP1 significantly contributes to diet-induced non-alcoholic steatohepatitis and fibrosis. This contribution is, in part, attributed to the regulation of intrahepatic immune cell infiltration and potential crosstalk between fat and the liver. These findings suggest that platelet-derived TSP1 may represent a novel therapeutic target in non-alcoholic fatty liver disease.

2.
Zootaxa ; 5410(3): 317-324, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480239

RESUMO

Two new species of the genus Nosphistica Meyrick, 1911 from China are described as new: N. eucalla sp. nov. and N. longiclavata sp. nov. Images of adults and genitalia for the newly described species and a checklist of the genus are given.


Assuntos
Lepidópteros , Mariposas , Animais , Distribuição Animal , China , Genitália
3.
Emerg Microbes Infect ; 13(1): 2337665, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38551145

RESUMO

Coxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.


Assuntos
Vacinas , Vacinas Virais , Humanos , Criança , Animais , Camundongos , Pré-Escolar , Anticorpos Antivirais , Anticorpos Neutralizantes , Imunização , Vacinação
4.
Zookeys ; 1192: 1-7, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419741

RESUMO

The lecithocerid genus Woonpaikia Park, 2010 and Woonpaikiaangoonae Park, 2010 are newly recorded from China. Woonpaikiasimilangoonae Yu & Wang, sp. nov. and W.imperspicua Yu & Wang, sp. nov. are described as new to science. Images of adults of the Chinese Woonpaikia species are provided, along with a key to the males of all the known species of Woonpaikia.

5.
EClinicalMedicine ; 69: 102468, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361990

RESUMO

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

6.
Zootaxa ; 5399(2): 101-129, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38221170

RESUMO

Ten new species of the genus Periacma Meyrick, 1894 are described: P. anterosinuata sp. nov., P. falcata sp. nov., P. largiloba sp. nov., P. laterispinulosa sp. nov., P. platygnatha sp. nov., P. ludingensis sp. nov., P. mediacantha sp. nov., P. securiformis sp. nov., P. solitaridens sp. nov. and P. subaequalis sp. nov. Periacma lianzhouensis (Wang, 2006) comb. nov. is transferred from the genus Irepacma to the present genus. The females of P. acriuncata Wang, Li & Liu, 2001, P. ferialis Meyrick, 1894, P. lianzhouensis (Wang, 2006), P. nepalensis Ueda et Moriuti, 1996 and P. rectignatha Wang et Li, 2006 are described for the first time. Periacma himalayensis Ueda et Moriuti, 1996, P. kunai Moriuti, Saito et Lewvanich, 1985, P. nakhonnayokensis Moriuti, Saito et Lewvanich, 1985 and P. nepalensis Ueda et Moriuti, 1996 are newly recorded for the Chinese fauna. Images of the new species and the newly described females are provided, and a global checklist of the described Periacma species is included.


Assuntos
Lepidópteros , Mariposas , Feminino , Animais , Distribuição Animal , Estruturas Animais , Tamanho do Órgão , China , Genitália
7.
Mol Metab ; 79: 101834, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37935315

RESUMO

Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role of cytokine, macrophage migration inhibitory factor (MIF) in regulating adipose HSL and adipocyte hypertrophy. Extracellular MIF downregulates HSL in an autocrine fashion, by activating the AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well as mice overexpressing MIF, both had high circulating MIF levels and showed suppression of HSL during the development of obesity. Blocking the extracellular action of MIF by a neutralizing MIF antibody significantly reduced obesity in HFD mice. Interestingly, intracellular MIF binds with COP9 signalosome subunit 5 (Csn5) and JNK, which leads to an opposing effect to inhibit JNK phosphorylation. With global MIF deletion, adipocyte JNK phosphorylation increased, resulting in decreased HSL expression, suggesting that the loss of MIF's intracellular inhibitory action on JNK was dominant in Mif-/- mice. Adipose tissue from Mif-/- mice also exhibited higher Akt and lower PKA phosphorylation following HFD feeding compared with WT, which may contribute to the downregulation of HSL activation during more severe obesity. Both intracellular and extracellular MIF have opposing effects to regulate HSL, but extracellular actions predominate to downregulate HSL and exacerbate the development of obesity during HFD.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Animais , Camundongos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Obesidade/metabolismo , Esterol Esterase/metabolismo
8.
EJNMMI Res ; 13(1): 105, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38052965

RESUMO

BACKGROUND: This study aimed to assess whether a combined model incorporating radiomic and depth features extracted from PET/CT can predict disease-free survival (DFS) in patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy. RESULTS: This study retrospectively included one hundred and five non-pCR patients. After a median follow-up of 71 months, 15 and 7 patients experienced recurrence and death, respectively. The primary tumor volume underwent feature extraction, yielding a total of 3644 radiomic features and 4096 depth features. The modeling procedure employed Cox regression for feature selection and utilized Cox proportional-hazards models to make predictions on DFS. Time-dependent receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to evaluate and compare the predictive performance of different models. 2 clinical features (RCB, cT), 4 radiomic features, and 7 depth features were significant predictors of DFS and were included to develop models. The integrated model incorporating RCB, cT, and radiomic and depth features extracted from PET/CT images exhibited the highest accuracy for predicting 5-year DFS in the training (AUC 0.943) and the validation cohort (AUC 0.938). CONCLUSION: The integrated model combining radiomic and depth features extracted from PET/CT images can accurately predict 5-year DFS in non-pCR patients. It can help identify patients with a high risk of recurrence and strengthen adjuvant therapy to improve survival.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38123967

RESUMO

BACKGROUND: To assess the applicability of the association between estimated glucose disposal rate (eGDR) and all-cause mortality in the elderly population, and the mediating role of brachial-ankle pulse wave velocity (baPWV). METHODS: This was a follow-up cohort study based on the cross-sectional survey of community-dwelling elderly. All participants in the study were included between September 2009 and June 2010, and the follow-up time was December 2020. Participants included 1862 Chinese community-dwelling elderly aged 60 years and above. Insulin resistance assessed by eGDR and arterial stiffness assessed by baPWV were the primary exposures of interest. Mortality, which was followed up until December 2020, was the primary outcome. Cox proportional hazards regression models were used to estimate the association of eGDR with mortality. The mediating effect of baPWV in this association was assessed by mediation analysis. RESULTS: A total of 1826 participants with a mean age of 71.03 years old were included in the study. During the median follow-up of 10.75 years, 334 participants died. The adjusted HR comparing the highest versus the lowest eGDR quartile was 0.22 (95% CI 0.09 to 0.54; p<0.001) in the Cox proportional hazards model. The results of mediation analysis showed that baPWV had a significant mediation impact on the link between eGDR and all-cause mortality both as continuous or categorical variables. CONCLUSION: eGDR is an independent predictor of all-cause mortality in the elderly population. baPWV partially mediated the association of eGDR and long-term all-cause mortality as a mediator factor.

10.
Sci Rep ; 13(1): 20193, 2023 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980376

RESUMO

Thrombospondin1 (TSP1) is a multifunctional matricellular protein. Previously, we demonstrated that TSP1 plays a pivotal role in obesity-related inflammation and insulin resistance (IR) by modulating macrophage accumulation and activation in adipose tissue. Moreover, in our in vitro studies, a CD36-derived peptide, functioning as a TSP1 antagonist, effectively inhibited TSP1-induced proinflammatory macrophage activation. However, whether this CD36 peptide can inhibit obesity-induced inflammation and IR in vivo is unknown and determined in this study in a high fat diet-induced obese mouse model (DIO). CD36 peptide or control peptide was intraperitoneally administered into the established obese mice triweekly for 6 weeks. We found that CD36 peptide treatment didn't affect obesity or weight gain but significantly reduced proinflammatory cytokine production systemically and in visceral fat tissue. Adipose tissue exhibited fewer crown-like structures and reduced macrophage infiltration. CD36 peptide treatment also attenuated the proinflammatory phenotype of bone marrow derived macrophages from obese mice. Furthermore, CD36 peptide treatment improved glucose tolerance and insulin sensitivity, and mitigated obesity-related fatty liver disease and kidney damage. Collectively, this study suggests that the CD36 peptide, as a TSP1 antagonist, shows promise as a novel therapeutic approach for managing obesity-related metabolic disorders.


Assuntos
Resistência à Insulina , Obesidade , Camundongos , Animais , Camundongos Obesos , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/genética , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/genética , Tecido Adiposo/metabolismo , Peptídeos/metabolismo , Camundongos Endogâmicos C57BL
11.
Transfus Apher Sci ; 62(6): 103840, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925341

RESUMO

Osteomyelitis is a refractory disease caused by microbial invasion of the bone, leading to destruction of the bone tissue. It is more common in children. Osteomyelitis requires long treatment at high cost and is associated with high rates of recurrence and disability. It can also be complicated by sepsis that, if not treated in time, can result in death. Here, we report the first case of a 10-year-old patient who presented with chronic tibial osteomyelitis complicated with fracture. The patient had received traditional treatment for osteomyelitis for over 14 months without success. However, after 4 months of treatment with autologous platelet-rich plasma, the fracture, infection, and osteomyelitis resolved completely. These clinical observations demonstrate the potential for using autologous platelet-rich plasma as a novel treatment for chronic pediatric osteomyelitis.


Assuntos
Osteomielite , Plasma Rico em Plaquetas , Humanos , Criança , Osteomielite/terapia , Osteomielite/complicações , Resultado do Tratamento
12.
Materials (Basel) ; 16(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37687728

RESUMO

Low reflectivity is of great significance to photoelectric devices, optical displays, solar cells, photocatalysis and other fields. In this paper, vanadium oxide is deposited on pattern SiO2 via atomic layer deposition and then annealed to characterize and analyze the anti-reflection effect. Scanning electron microscope (SEM) images indicate that the as-deposited VOx film has the advantages of uniformity and controllability. After annealing treatment, the VO2@pattern SiO2 has fewer crevices compared with VO2 on the accompanied planar SiO2 substrate. Raman results show that there is tiny homogeneous stress in the VO2 deposited on pattern SiO2, which dilutes the shrinkage behavior of the crystallization process. The optical reflection spectra indicate that the as-deposited VOx@pattern SiO2 has an anti-reflection effect due to the combined mechanism of the trapping effect and the effective medium theory. After annealing treatment, the weighted average reflectance diminished to 1.46% in the visible near-infrared wavelength range of 650-1355 nm, in which the absolute reflectance is less than 2%. Due to the multiple scattering effect caused by the tiny cracks generated through annealing, the anti-reflection effect of VO2@pattern SiO2 is superior to that of VOx@pattern SiO2. The ultra-low reflection frequency domain amounts to 705 nm, and the lowest absolute reflectance emerges at 1000 nm with an astonishing value of 0.86%. The prepared anti-reflective materials have significant application prospects in the field of intelligent optoelectronic devices due to the controllability of atomic layer deposition (ALD) and phase transition characteristics of VO2.

13.
Chronic Dis Transl Med ; 9(3): 250-257, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37711862

RESUMO

Background: It is of great clinical significance to further explore new strategies and potential combined therapeutic targets for gastric cancer. This study aimed to investigate the synthetic lethal effect of RBBP8 molecular intervention combined with a poly ADP ribose polymerase (PARP) inhibitor in non-BRCA mutant gastric cancer and clarify the mechanism by which RBBP8 regulates homologous recombination repair. Methods: The role of RBBP8 in DNA damage repair was observed using bioinformatic analysis, western blot analysis, and immunofluorescence. The synthetic lethal effect was verified using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS)and flow cytometry apoptosis experiments. Results: Among the patients with gastric cancer treated with chemotherapy, the prognosis of patients with high RBBP8 expression levels was worse (homologous recombination [HR] = 1.54, p = 0.028). RBBP8 knockdown induced DNA damage and had a synergistic effect with PARP inhibitor treatment on cell viability inhibition and cell apoptosis in AGS (generic code for human gastric adenocarcinoma cells) (t = 11.154, p < 0.001) and N87 (t = 6.362, p < 0.001) cells. RBBP8 knockdown inhibited RAD51 activation and DNA terminal excision in homologous recombination repair. Conclusion: RBBP8 is involved in homologous recombination repair, and molecular intervention into RBBP8 could achieve a synthetic lethal effect with PARP inhibitor treatment in gastric cancer cells.

14.
BMC Geriatr ; 23(1): 582, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735635

RESUMO

BACKGROUND: Older people with hypertension may have more complex multisystem problems and a higher risk of morbidity and mortality. We aimed to examine the association of cognitive impairment (CI) and diabetes mellitus (DM) on all-cause mortality in the aged with hypertension (HTN). METHODS: This is a prospective cohort study with a sample of 1017 older people with hypertension aged 60 years or older who completed baseline examinations in 2009-2010 and followed up for ten years in 2020. The endpoint was death from any cause. Subjects were categorized as HTN only, HTN + DM, HTN + CI, and HTN + DM + CI. Cox regression model was used to determine the association of comorbidities on all-cause mortality. RESULTS: During the 10-year follow-up period, 196 deaths occurred. After adjusted for covariates, risk of death from any cause was significantly increased in the older people with increased comorbidities (P = 0.003). Compared with the HTN only, with HTN + CI, and HTN + DM + CI, the HRs (95% confidence intervals) for all-cause mortality were 1.61(1.13-2.30) and 1.79(1.07-2.99), respectively. In stratified analyses, the relationship between comorbidities level and the risk of all-cause mortality persisted. CONCLUSION: All-cause mortality risks increased with increasing the comorbidities. This study emphasizes the importance of comprehensive management of the older people with HTN in clinical practice and public health policy.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Hipertensão , Idoso , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , População do Leste Asiático , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade
15.
Nat Prod Bioprospect ; 13(1): 29, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698689

RESUMO

More and more evidence suggests that puerarin, a potential remedy for gut inflammation, may have an ameliorative effect on sleep disturbances. However, the relationship between puerarin and sleep disruption has not been extensively researched. This study aims to explore the role and mechanisms of puerarin in improving sleep disorders. We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests. Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver, lung, and kidney. Puerarin reversed multi-organ damage and inflammation. Further, puerarin activated paneth cells, resulting in increased lysozyme and TGF-ß production, and stimulating intestinal stem cell proliferation. Puerarin also effectively inhibited the expression of F4/80, iNOS, TNF-α, and IL-1ß in the small intestine, while it increased Chil3, CD206, and Arg-1 levels. Moreover, puerarin treatment significantly decreased P-P65, TLR4, Bcl-xl, and cleaved caspase-3 protein levels while increasing barrier protein levels, including ZO-1, Occludin, Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut. Overall, puerarin diminished systemic inflammation, particularly intestinal inflammation, and enhanced intestinal barrier integrity in mice with sleep disorders. Our findings suggest a potential new therapeutic pathway for sleep disorders.

18.
Zootaxa ; 5297(4): 451-482, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37518783

RESUMO

Thirty species of the genus Calamotropha Zeller, 1863 from China are reviewed. Five species are described as new: C. bleszynskii Kim & Li, sp. nov., C. duovirgata Kim & Li, sp. nov., C. nigerifera Kim & Li, sp. nov., C. parallela Kim & Li, sp. nov. and C. parvispina Kim & Li, sp. nov.; two species are newly recorded for China: C. alcesta Bleszynski, 1961 and C. punctivenella (Hampson, 1896). The female of C. sperlingi Li, 2019 is described for the first time. Calamotropha multicornuella Chen & Song, 2002 syn. nov. is synonymized with C. sienkiewiczi Bleszynski, 1961, and C. sawtoothella Chen & Song, 2002 syn. nov. is synonymized with C. latella (Snellen, 1890). Images of adults and genitalia of 28 known species with available specimens are provided, except images of genitalia provided by Li & Li in 2012. A key to the known Calamotropha species in China is included.

19.
Biochem Biophys Res Commun ; 676: 78-83, 2023 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-37499367

RESUMO

Our previous studies demonstrated that mice with global CD47 deficiency are lean and resistant to diet or aging-associated obesity and metabolic complications. This protective effect is partially through modulating brown fat function. To definitively determine the role of brown fat CD47 in age-related metabolic homeostasis, inducible brown adipocyte-specific cd47 deficient mice were generated by crossbreeding cd47 floxed mice with UCP1-CreERT2 mice and characterized in this study. Efficient knockdown of CD47 in brown fat was achieved in both male and female mice through tamoxifen administration. Intriguingly, our findings indicated that male mice lacking CD47 in brown fat displayed a notable reduction in body weight starting at 23 weeks of age when housed at a temperature of 22 °C, in comparison to control mice. This reduction in weight was accompanied by improved glucose tolerance. Remarkably, this phenotype persisted even when the male mice were housed under thermoneutral conditions (30 °C). Conversely, female knockout mice did not exhibit significant changes in weight throughout the study. In addition to the enhanced glucose homeostasis, brown fat CD47 deficiency in male mice also prevented age-related hypertriglyceridemia and non-alcoholic fatty liver disease. Furthermore, the brown fat tissue of male knockout mice exhibited reduced whitening, while maintaining comparable levels of thermogenic markers. This suggests the involvement of a thermogenesis-independent mechanism. Altogether, these findings highlight a sex difference in the impact of brown adipocyte CD47 deficiency on age-related weight changes and glucose homeostasis.


Assuntos
Adipócitos Marrons , Antígeno CD47 , Feminino , Camundongos , Animais , Masculino , Adipócitos Marrons/metabolismo , Antígeno CD47/genética , Antígeno CD47/metabolismo , Caracteres Sexuais , Camundongos Knockout , Tecido Adiposo Marrom/metabolismo , Homeostase , Glucose/metabolismo , Termogênese/genética , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos
20.
Eur J Nucl Med Mol Imaging ; 50(12): 3630-3646, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37474736

RESUMO

PURPOSE: The goal of this work is to demonstrate the feasibility of directly generating attenuation-corrected PET images from non-attenuation-corrected (NAC) PET images for both rest and stress-state static or dynamic [13N]ammonia MP PET based on a generative adversarial network. METHODS: We recruited 60 subjects for rest-only scans and 14 subjects for rest-stress scans, all of whom underwent [13N]ammonia cardiac PET/CT examinations to acquire static and dynamic frames with both 3D NAC and CT-based AC (CTAC) PET images. We developed a 3D pix2pix deep learning AC (DLAC) framework via a U-net + ResNet-based generator and a convolutional neural network-based discriminator. Paired static or dynamic NAC and CTAC PET images from 60 rest-only subjects were used as network inputs and labels for static (S-DLAC) and dynamic (D-DLAC) training, respectively. The pre-trained S-DLAC network was then fine-tuned by paired dynamic NAC and CTAC PET frames of 60 rest-only subjects to derive an improved D-DLAC-FT for dynamic PET images. The 14 rest-stress subjects were used as an internal testing dataset and separately tested on different network models without training. The proposed methods were evaluated using visual quality and quantitative metrics. RESULTS: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods were consistent with clinical CTAC in terms of various images and quantitative metrics. The S-DLAC (slope = 0.9423, R2 = 0.947) showed a higher correlation with the reference static CTAC as compared to static NAC (slope = 0.0992, R2 = 0.654). D-DLAC-FT yielded lower myocardial blood flow (MBF) errors in the whole left ventricular myocardium than D-DLAC, but with no significant difference, both for the 60 rest-state subjects (6.63 ± 5.05% vs. 7.00 ± 6.84%, p = 0.7593) and the 14 stress-state subjects (1.97 ± 2.28% vs. 3.21 ± 3.89%, p = 0.8595). CONCLUSION: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods achieve comparable performance with clinical CTAC. Transfer learning shows promising potential for dynamic MP PET.


Assuntos
Amônia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Tomografia por Emissão de Pósitrons/métodos
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