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1.
Development ; 151(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602507

RESUMO

CFAP58 is a testis-enriched gene that plays an important role in the sperm flagellogenesis of humans and mice. However, the effect of CFAP58 on bull semen quality and the underlying molecular mechanisms involved in spermatogenesis remain unknown. Here, we identified two single-nucleotide polymorphisms (rs110610797, A>G and rs133760846, G>T) and one indel (g.-1811_ g.-1810 ins147bp) in the promoter of CFAP58 that were significantly associated with semen quality of bulls, including sperm deformity rate and ejaculate volume. Moreover, by generating gene knockout mice, we found for the first time that the loss of Cfap58 not only causes severe defects in the sperm tail, but also affects the manchette structure, resulting in abnormal sperm head shaping. Cfap58 deficiency causes an increase in spermatozoa apoptosis. Further experiments confirmed that CFAP58 interacts with IFT88 and CCDC42. Moreover, it may be a transported cargo protein that plays a role in stabilizing other cargo proteins, such as CCDC42, in the intra-manchette transport/intra-flagellar transport pathway. Collectively, our findings reveal that CFAP58 is required for spermatogenesis and provide genetic markers for evaluating semen quality in cattle.


Assuntos
Análise do Sêmen , Sêmen , Humanos , Bovinos , Masculino , Animais , Camundongos , Cabeça do Espermatozoide , Espermatozoides , Camundongos Knockout
2.
J Orthop Surg Res ; 19(1): 254, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649974

RESUMO

BACKGROUND: The one-hole split endoscopy (OSE) was first proposed and clinically applied in China in 2019. The aim of this study was to compare the clinical efficacy of one-hole split endoscopy (OSE) and unilateral biportal endoscopy (UBE) for treating lumbar spinal stenosis (LSS). METHODS: One hundred sixty patients with LSS who met the inclusion from November 2020 to August 2022 were analyzed and divided into OSE and UBE groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the two groups. After matching, surgical outcomes were recorded, and clinical data, including functional scores and imaging findings, were compared. Functional scores included the visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), the Japanese Orthopedic Association score (JOA), and the Oswestry Disability Index (ODI). Imaging data included dural sac cross-sectional area (DCSA), lumbar range of motion (ROM), and sagittal translation (ST). RESULTS: After PSM, 104 LSS patients were included in the study, and all covariates were well-balanced between the two groups. Among the matched patients, the OSE showed advantages over the UBE regarding operative time (62.42 ± 4.86 vs. 68.96 ± 4.56) and incision length (2.30 ± 0.14 vs. 2.70 ± 0.15) (P < 0.001). However, differences between the two groups in intraoperative blood loss, hospital length of stay, and complication rates were not statistically significant (P > 0.05). There was no statistically significant difference regarding VAS-BP, VAS-LP, JOA, and ODI between the two groups (P > 0.05). However, all clinical and functional scores significantly improved postoperatively (P < 0.05). Postoperative DCSA of both groups was significantly found to be improved (P < 0.05), ROM and ST remained within the normal range, and no cases of lumbar instability were recorded. According to the modified MacNab criteria, the excellent and good rates in the OSE and UBE groups were 94.23% and 90.38%, respectively, with no statistically significant difference (P = 0.713). CONCLUSION: OSE is an alternative technique to UBE for the treatment of LSS, with similar satisfactory clinical outcomes, shorter operative time, and smaller incision length. Further studies are needed for long-term efficacy.


Assuntos
Endoscopia , Vértebras Lombares , Pontuação de Propensão , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Estenose Espinal/diagnóstico por imagem , Masculino , Feminino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Endoscopia/métodos , Idoso , Resultado do Tratamento , Endoscópios
3.
Bioresour Bioprocess ; 11(1): 42, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653936

RESUMO

Fungal endophytes, as an untapped resource of glycoside hydrolase biocatalysts, need to be further developed. Mogroside V, the primary active compound in Siraitia grosvenorii fruit, can be converted into other various bioactive mogrosides by selective hydrolysis of glucose residues at C3 and C24 positions. In present study, 20 fungal strains were randomly selected from our endophytic fungal strain library to assess their capability for mogroside V transformation. The results revealed that relatively high rate (30%) endophytic fungal strains exhibited transformative potential. Further analysis indicated that endophytic fungi could produce abundant mogrosides, and the pathways for biotransforming mogroside V showed diverse. Among the given fungal endophytes, Aspergillus sp. S125 almost completely converted mogroside V into the end-products mogroside II A and aglycone within just 2 days of fermentation; Muyocopron sp. A5 produced rich intermediate products, including siamenoside I, and the end-product mogroside II E. Subsequently, we optimized the fermentation conditions for Aspergillus sp. S125 and Muyocopron sp. A5 to evaluate the feasibility of large-scale mogroside V conversion. After optimization, Aspergillus sp. S125 converted 10 g/L of mogroside V into 4.5 g/L of mogroside II A and 3.6 g/L of aglycone after 3 days of fermentation, whereas Muyocopron sp. A5 selectively produced 4.88 g/L of siamenoside I from 7.5 g/L of mogroside V after 36 h of fermentation. This study not only identifies highly effective biocatalytic candidates for mogrosides transformation, but also strongly suggests the potential of plant endophytic fungi as valuable resources for the biocatalysis of natural compounds.

4.
Adv Mater ; 36(21): e2312303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372628

RESUMO

Multi-dimensional multiplexed metasurface holography extends holographic information capacity and promises revolutionary advancements for vivid imaging, information storage, and encryption. However, achieving multifunctional metasurface holography by forward design method is still difficult because it relies heavily on Jones matrix engineering, which places high demands on physical knowledge and processing technology. To break these limitations and simplify the design process, here, an end-to-end inverse design framework is proposed. By directly linking the metasurface to the reconstructed images and employing a loss function to guide the update of metasurface, the calculation of hologram can be omitted; thus, greatly simplifying the design process. In addition, the requirements on the completeness of meta-library can also be significantly reduced, allowing multi-channel hologram to be achieved using meta-atoms with only two degrees of freedom, which is very friendly to processing. By exploiting the proposed method, metasurface hologram containing up to 12 channels of multi-wavelength, multi-plane, and multi-polarization is designed and experimentally demonstrated, which exhibits the state-of-the-art information multiplexing capacity of the metasurface composed of simple meta-atoms. This method is conducive to promoting the intelligent design of multifunctional meta-devices, and it is expected to eventually accelerate the application of meta-devices in colorful display, imaging, storage and other fields.

5.
Small ; 20(5): e2304966, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752777

RESUMO

The advent of 3D printing has facilitated the rapid fabrication of microfluidic devices that are accessible and cost-effective. However, it remains a challenge to fabricate sophisticated microfluidic devices with integrated structural and functional components due to limited material options of existing printing methods and their stringent requirement on feedstock material properties. Here, a multi-materials multi-scale hybrid printing method that enables seamless integration of a broad range of structural and functional materials into complex devices is reported. A fully printed and assembly-free microfluidic biosensor with embedded fluidic channels and functionalized electrodes at sub-100 µm spatial resolution for the amperometric sensing of lactate in sweat is demonstrated. The sensors present a sensitive response with a limit of detection of 442 nm and a linear dynamic range of 1-10 mm, which are performance characteristics relevant to physiological levels of lactate in sweat. The versatile hybrid printing method offers a new pathway toward facile fabrication of next-generation integrated devices for broad applications in point-of-care health monitoring and sensing.


Assuntos
Técnicas Biossensoriais , Dispositivos Lab-On-A-Chip , Microfluídica , Técnicas Biossensoriais/métodos , Impressão Tridimensional , Lactatos
6.
Heliyon ; 9(12): e22797, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125451

RESUMO

The aim of this systematic review is to assess the effects of structured resistance training programs on the throwing performance and injury risk of baseball players, irrespective of their age or sex. The literature search was carried out on 18/10/2023, utilizing databases that include PubMed, Scopus, and the Web of Science. Our inclusion criteria encompassed research involving baseball players of all ages and sex who had undergone resistance-based training interventions. For comparison, we considered active control groups, irrespective of their exposure to additional training programs. The outcomes under investigation were related to throwing performance (i.e., throwing velocity and accuracy) and injuries associated with throwing. In our review, we exclusively included studies with a two- or multi-arm design. We evaluated the risk of bias using the PEDro scale. Out of the initial pool of 509 studies, we carefully examined 27 full-text articles and ultimately selected and analyzed 16 studies for inclusion in our review. Out of the 12 studies that compared and presented the inferential statistics for the post-training effects of the experimental versus control groups, it was observed that 8 of these studies demonstrated a significantly more favorable impact of the experimental group on enhancing throwing velocity when compared to the control group. Out of the three studies that compared the experimental and control groups in terms of throwing accuracy, only one study showed a significant improvement in the experimental group compared to the control group after the intervention. In conclusion, this systematic review indicates that resistance-based training interventions appear to be effective in enhancing throwing velocity. However, the evidence regarding the efficacy of these interventions in improving throwing accuracy is less robust. It is worth noting that while some experimental conditions may lead to an increase in injury rates, there is limited data available on this aspect, with only a few studies reporting on this variable.

7.
Artigo em Inglês | MEDLINE | ID: mdl-37855357

RESUMO

BACKGROUND: In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet ß-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic ß-cells. AIMS: Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic ßcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention. METHODS: The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells. RESULTS: High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets. CONCLUSION: Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

8.
Herit Sci ; 11(1): 223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869744

RESUMO

In recent years, the conservation and protection of ancient cultural heritage have received increasing attention, and non-destructive testing (NDT), which can minimize the damage done to the test subject, plays an integral role therein. For instance, NDT through active infrared thermal imaging can be applied to ancient polyptychs, which can realize accurate detection of damage and defects existing on the surface and interior of the polyptychs. In this study, infrared thermography is used for non-invasive investigation and evaluation of two polyptych samples with different pigments and artificial defects, but both reproduced based on a painting by Pietro Lorenzetti (1280/85-1348) using the typical tempera technique of the century. It is noted that, to avoid as far as possible secondary damages done to the ancient cultural heritages, repeated damage-detection experiments are rarely carried out on the test subjects. To that end, numerical simulation is used to reveal the heat transfer properties and temperature distributions, as to perform procedural verification and reduce the number of experiments that need to be conducted on actual samples. Technique-wise, to improve the observability of the experimental results, a total variation regularized low-rank tensor decomposition algorithm is implemented to reduce the background noise and improve the contrast of the images. Furthermore, the efficacy of image processing is quantified through the structural-similarity evaluation.

9.
Front Psychol ; 14: 1227931, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529314

RESUMO

Background and objectives: Concern exists regarding the potential negative consequences of smartphone addiction among adolescents. This study investigated the effect of use motivations and alexithymia on smartphone addiction among adolescents with two insecure attachment styles, namely, anxious and avoidant attachment. These attachment styles were regarded as mediating variables. Methods: Self-report measures were used to assess use motivations, alexithymia, insecure attachment and smartphone addiction. Data were collected from 748 junior high school students (382 males and 366 females) in northeastern China. Structural equation modeling was used to test our hypothesis that use motivations and alexithymia are directly associated with smartphone addiction and also through the mediation of attachment insecurities. Results: The structural equation modeling results showed a strong and positive correlation between use motivation and smartphone addiction, with avoidant attachment mediating such a relationship. Meanwhile, the two components of alexithymia, difficulty identifying feelings and externally oriented thinking, positively predicted smartphone addiction, with avoidant attachment serving as a mediator of this effect. In addition, the mediation analysis results demonstrated that attachment anxiety mediated the connection between escape drive, extrinsically focused thought, and smartphone addiction. Conclusion: Findings describe how attachment insecurities, smartphone use motivations, and alexithymia can interact with one another to predict smartphone addiction. Smartphone use motivation types and alexithymia symptoms should be taken into consideration when designing targeted intervention programs for smartphone addiction to address the different attachment needs of adolescents, which would be helpful to reduce their smartphone addiction behaviors.

10.
EMBO J ; 42(19): e112814, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37635626

RESUMO

The regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.


Assuntos
Proteínas de Saccharomyces cerevisiae , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/metabolismo , Fagossomos/metabolismo , Fosforilação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
11.
World J Gastroenterol ; 29(22): 3519-3533, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37389231

RESUMO

BACKGROUND: It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival. AIM: To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification. METHODS: Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective ß-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). RESULTS: A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48). CONCLUSION: TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.


Assuntos
Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Masculino , Humanos , Pessoa de Meia-Idade , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/etiologia , Estudos Retrospectivos , Sobrevivência de Enxerto , Pressão na Veia Porta
12.
Nature ; 617(7960): 292-298, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37165239

RESUMO

The development of new materials and their compositional and microstructural optimization are essential in regard to next-generation technologies such as clean energy and environmental sustainability. However, materials discovery and optimization have been a frustratingly slow process. The Edisonian trial-and-error process is time consuming and resource inefficient, particularly when contrasted with vast materials design spaces1. Whereas traditional combinatorial deposition methods can generate material libraries2,3, these suffer from limited material options and inability to leverage major breakthroughs in nanomaterial synthesis. Here we report a high-throughput combinatorial printing method capable of fabricating materials with compositional gradients at microscale spatial resolution. In situ mixing and printing in the aerosol phase allows instantaneous tuning of the mixing ratio of a broad range of materials on the fly, which is an important feature unobtainable in conventional multimaterials printing using feedstocks in liquid-liquid or solid-solid phases4-6. We demonstrate a variety of high-throughput printing strategies and applications in combinatorial doping, functional grading and chemical reaction, enabling materials exploration of doped chalcogenides and compositionally graded materials with gradient properties. The ability to combine the top-down design freedom of additive manufacturing with bottom-up control over local material compositions promises the development of compositionally complex materials inaccessible via conventional manufacturing approaches.

13.
J Xray Sci Technol ; 31(4): 713-729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37092210

RESUMO

BACKGROUND: Chest CT scan is an effective way to detect and diagnose COVID-19 infection. However, features of COVID-19 infection in chest CT images are very complex and heterogeneous, which make segmentation of COVID-19 lesions from CT images quite challenging. OBJECTIVE: To overcome this challenge, this study proposes and tests an end-to-end deep learning method called dual attention fusion UNet (DAF-UNet). METHODS: The proposed DAF-UNet improves the typical UNet into an advanced architecture. The dense-connected convolution is adopted to replace the convolution operation. The mixture of average-pooling and max-pooling acts as the down-sampling in the encoder. Bridge-connected layers, including convolution, batch normalization, and leaky rectified linear unit (leaky ReLU) activation, serve as the skip connections between the encoder and decoder to bridge the semantic gap differences. A multiscale pyramid pooling module acts as the bottleneck to fit the features of COVID-19 lesion with complexity. Furthermore, dual attention feature (DAF) fusion containing channel and position attentions followed the improved UNet to learn the long-dependency contextual features of COVID-19 and further enhance the capacity of the proposed DAF-UNet. The proposed model is first pre-trained on the pseudo label dataset (generated by Inf-Net) containing many samples, then fine-tuned on the standard annotation dataset (provided by the Italian Society of Medical and Interventional Radiology) with high-quality but limited samples to improve performance of COVID-19 lesion segmentation on chest CT images. RESULTS: The Dice coefficient and Sensitivity are 0.778 and 0.798 respectively. The proposed DAF-UNet has higher scores than the popular models (Att-UNet, Dense-UNet, Inf-Net, COPLE-Net) tested using the same dataset as our model. CONCLUSION: The study demonstrates that the proposed DAF-UNet achieves superior performance for precisely segmenting COVID-19 lesions from chest CT scans compared with the state-of-the-art approaches. Thus, the DAF-UNet has promising potential for assisting COVID-19 disease screening and detection.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico por imagem , Tomografia Computadorizada por Raios X
14.
Epigenetics ; 18(1): 2183339, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36866611

RESUMO

DNA methylation and gene alternative splicing drive spermatogenesis. In screening DNA methylation markers and transcripts related to sperm motility, semen from three pairs of full-sibling Holstein bulls with high and low motility was subjected to reduced representation bisulphite sequencing. A total of 948 DMRs were found in 874 genes (gDMRs). Approximately 89% of gDMR-related genes harboured alternative splicing events, including SMAD2, KIF17, and PBRM1. One DMR in exon 29 of PBRM1 with the highest 5mC ratio was found, and hypermethylation in this region was related to bull sperm motility. Furthermore, alternative splicing events at exon 29 of PBRM1 were found in bull testis, including PBRM1-complete, PBRM1-SV1 (exon 28 deletion), and PBRM1-SV2 (exons 28-29 deletion). PBRM1-SV2 exhibited significantly higher expression in adult bull testes than in newborn bull testes. In addition, PBRM1 was localized to the redundant nuclear membrane of bull sperm, which might be related to sperm motility caused by sperm tail breakage. Therefore, the hypermethylation of exon 29 may be associated with the production of PBRM1-SV2 in spermatogenesis. These findings indicated that DNA methylation alteration at specific loci could regulate gene splicing and expression and synergistically alter sperm structure and motility.


Assuntos
Metilação de DNA , Sêmen , Masculino , Bovinos , Animais , Processamento Alternativo , Motilidade dos Espermatozoides/genética , Espermatozoides
15.
Front Endocrinol (Lausanne) ; 14: 1145847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998481

RESUMO

Objective: To identify risk factors for impaired glucose regulation (IGR) and assess their impact on community residents, this study used a questionnaire to conduct cross-sectional surveys and analysis. Methods: Overall, 774 residents of an urban community in northern China (Jian city) participated in this study. Trained investigators conducted surveys using questionnaires. Based on their medical history, respondents were divided into three glucose status groups as follows: normal (NGT), IGR, and diabetes mellitus (DM). Statistical analysis of survey data was performed using SPSS v. 22.0. Results: Age, hypertension, family history of diabetes (FHD), dyslipidemia, obesity, and cardiovascular and cerebral disease (CVD) were positively correlated with IGR in men and women. IGR was negatively correlated with a sedentary lifestyle in men and positively correlated with being overweight in women. The number of type 2 diabetes mellitus (T2D) risk factors per subject was positively correlated with age in the NGT group. Glucose status deteriorated with increasing age and the number of risk factors. FHD was the strongest risk factor in both men and women. Conclusions: Prevention of IGR includes weight control, physical activity, and prevention of hypertension and dyslipidemia, especially in subjects with FHD.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Masculino , Humanos , Feminino , Glucose , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Fatores de Risco , Hipertensão/complicações
16.
Front Endocrinol (Lausanne) ; 14: 1123124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843575

RESUMO

The UFM1 conjugation system(UFMylation)is a novel type of ubiquitin-like system that plays an indispensable role in maintaining cell homeostasis under various cellular stress. Similar to ubiquitination, UFMylation consists of a three-step enzymatic reaction with E1-like enzymes ubiquitin-like modifier activating enzyme5 (UBA5), E2-like enzymes ubiquitin-fold modifier-conjugating enzyme 1(UFC1), and E3-like ligase UFM1-specific ligase 1 (UFL1). As the only identified E3 ligase, UFL1 is responsible for specific binding and modification of the substrates to mediate numerous hormone signaling pathways and endocrine regulation under different physiological or pathological stress, such as ER stress, genotoxic stress, oncogenic stress, and inflammation. Further elucidation of the UFL1 working mechanism in multiple cellular stress responses is essential for revealing the disease pathogenesis and providing novel potential therapeutic targets. In this short review, we summarize the recent advances in novel UFL1 functions and shed light on the potential challenges ahead, thus hopefully providing a better understanding of UFMylation-mediated cellular stress.


Assuntos
Proteínas , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/genética , Proteínas/metabolismo , Ubiquitinação , Ubiquitina/metabolismo
17.
Int J Biol Macromol ; 234: 123714, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36806767

RESUMO

Streptococcus agalactiae, as one of the main pathogens of clinical and subclinical mastitis, affects animal welfare and leads to huge economic losses to farms due to the sharp decline in milk yield. However, both the real pathogenic mechanisms of S. agalactiae-induced mastitis and the regulator which controls the inflammation and autophagy are largely unknown. Served as a substrate of ubiquitin-like proteins of E3 ligase, CDK5RAP3 is widely involved in the regulation of multiple signaling pathways. Our findings revealed that CDK5RAP3 was significantly down-regulated in mastitis infected by S. agalactiae. Surprisingly, inflammasome activation was triggered by CDK5RAP3 knockdown: up-regulated NLRP3, IL1ß and IL6, and cleaved caspase1 promoting by NF-κB, thereby resulting in pyroptosis. Additionally, the accumulation of autophagy markers (LC3B and p62) after CDK5RAP3 knockdown suggested that the autophagolysosome degradation pathway was inhibited, thereby activating the NF-κB pathway and NLRP3 inflammasome. Hence, our findings suggest that downregulation or ablation of CDK5RAP3 inhibits autophagolysosome degradation, causes inflammation by activating the NF-κB /NLRP3 inflammasome, and triggers cell death. In conclusion, CDK5RAP3 holds the key to understanding the interaction between autophagy and immune responses, its anti-inflammatory role in this study will throw new light on the clinical drug discovery to cure S. agalactiae mastitis.


Assuntos
Inflamassomos , Mastite , Animais , Feminino , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Inflamação/patologia , Mastite/genética , Mastite/patologia , Proteínas de Ciclo Celular , Proteínas Supressoras de Tumor
18.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36617259

RESUMO

Cold climate shapes the genome of animals and drives them to carry sufficient genetic variations to adapt to changes in temperature. However, limited information is available about the genome-wide pattern of adaptations to cold environments in cattle. In the present study, we used 777K SNP genotyping (15 Chinese cattle breeds, 198 individuals) and whole genome resequencing data (54 cattle breeds of the world, 432 individuals) to disentangle divergent selection signatures, especially between the cold-adapted (annual average temperature of habitat, 6.24 °C to 10.3 °C) and heat-adapted (20.2 °C to 24.73 °C) Chinese native cattle breeds. Genomic analyses revealed a set of candidate genes (e.g., UQCR11, DNAJC18, EGR1, and STING1) were functionally associated with thermogenesis and energy metabolism. We also characterized the adaptive loci of cattle exposed to cold temperatures. Our study finds new candidate genes and provides new insights into adaptations to cold climates in cattle.


Cold climates can affect cattle performance, survival, and health. Local cattle breeds have been adapted to the local environments including extremely cold temperatures after a long period of natural and artificial selection. Selection and local adaptation are shaping populations. However, identifying loci associated with cold adaptation has been a major challenge. We used high-density SNP arrays and resequencing data to comprehensively analyze and compare the genomic selection signatures of Chinese northern and southern cattle, and elucidated several adaptive genes and alleles involved in cold adaptation. The complexity of genetic adaptation mechanism among different low-temperature adapted cattle breeds was also emphasized.


Assuntos
Clima Frio , Genoma , Bovinos , Animais , Genômica , Aclimatação , Variação Genética , Seleção Genética , Polimorfismo de Nucleotídeo Único
19.
Proc Natl Acad Sci U S A ; 120(1): e2215126120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574691

RESUMO

Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13-Mec1 interaction revealed two previously unrecognized protein regions, the Mec1-Binding Region (MBR) on Atg13 and the Atg13-Binding Region (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS.


Assuntos
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Quinases/metabolismo , Glucose/metabolismo , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
20.
Global Spine J ; 13(6): 1509-1521, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34530635

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVE: To compare the clinical efficacy of posterior lumbar laminectomy decompression under full endoscopic technique (Endo-LOVE) and percutaneous endoscopic medial foraminal decompression (PE-MFD) in the treatment of degenerative lumbar spinal stenosis (DLSS). METHODS: Between April 2017 and April 2018, 96 patients with DLSS underwent Endo-LOVE or PE-MFD, including 58 with Endo-LOVE and 38 with PE-MFD. After propensity score matching (PSM), patient characteristics, operation time, intraoperative fluoroscopy times, postoperative bedridden time, hospital stay and postoperative complications were recorded and compared. The clinical efficacy was evaluated according to Oswestry disability index (ODI), visual analogue scale (VAS), lumbar disease JOA and modified MacNab criteria. RESULTS: A total of 96 patients with DLSS were included in the study. After PSM, the 2 groups were comparable in patient demographic and baseline characteristics. The operation time and intraoperative fluoroscopy times in PE-MFD group were significantly more than those in Endo-LOVE group (P < .05). The operation time in PE-MFD group was significantly less than that in Endo-LOVE group (P < .05).The intraoperative fluoroscopy times in PE-MFD group were significantly more than that in Endo-LOVE group (P < .05). The ODI, VAS and lumbar disease JOA in the 2 groups were significantly improved comparing with those before operation (P < .05). According to the modified MacNab criteria, the excellent and good rates of the 2 groups were 93.5% in Endo-LOVE group and 87.1% in PE-MFD group (P > .05). CONCLUSION: Endo-LOVE and PE-MFD technique can both effectively treat DLSS, and the short-term follow-up results are positive. Endo-LOVE technique has the advantages of fast puncture positioning, less radiation exposure and wider indications. However, PE-MFD needs more radiation exposure and has the possibility of incomplete decompression for complex multiplanar spinal stenosis.

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