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1.
Nat Commun ; 15(1): 3181, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609351

RESUMO

The dynamic control of electromagnetic waves is a persistent pursuit in modern industrial development. The state-of-the-art dynamic devices suffer from limitations such as narrow bandwidth, limited modulation range, and expensive features. To address these issues, we fuse origami techniques with metamaterial design to achieve ultra-wideband and large-depth reflection modulation. Through a folding process, our proposed metamaterial achieves over 10-dB modulation depth over 4.96 - 38.8 GHz, with a fractional bandwidth of 155% and tolerance to incident angles and polarizations. Its ultra-wideband and large-depth reflection modulation performance is verified through experiments and analyzed through multipole decomposition theory. To enhance its practical applicability, transparent conductive films are introduced to the metamaterial, achieving high optical transparency (>87%) from visible to near-infrared light while maintaining cost-effectiveness. Benefiting from lightweight, foldability, and low-cost properties, our design shows promise for extensive satellite communication and optical window mobile communication management.

2.
PeerJ ; 12: e16984, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426132

RESUMO

Background: Wheat (Tritium aestivum L.) production is critical for global food security. In recent years, due to climate change and the prolonged growing period of rice varieties, the delayed sowing of wheat has resulted in a loss of grain yield in the area of the middle and lower reaches of the Yangtze River. It is of great significance to screen for natural germplasm resources of wheat that are resistant to late sowing and to explore genetic loci that stably control grain size and yield. Methods: A collection of 327 wheat accessions from diverse sources were subjected to genome-wide association studies using genotyping-by-sequencing. Field trials were conducted under normal, delayed, and seriously delayed sowing conditions for grain length, width, and thousand-grain weight at two sites. Additionally, the additive main effects and multiplicative interaction (AMMI) model was applied to evaluate the stability of thousand-grain weight of 327 accessions across multiple sowing dates. Results: Four wheat germplasm resources have been screened, demonstrating higher stability of thousand-grain weight. A total of 43, 35, and 39 significant MTAs were determined across all chromosomes except for 4D under the three sowing dates, respectively. A total of 10.31% of MTAs that stably affect wheat grain size could be repeatedly identified in at least two sowing dates, with PVE ranging from 0.03% to 38.06%. Among these, six were for GL, three for GW, and one for TGW. There were three novel and stable loci (4A_598189950, 4B_307707920, 2D_622241054) located in conserved regions of the genome, which provide excellent genetic resources for pyramid breeding strategies of superior loci. Our findings offer a theoretical basis for cultivar improvement and marker-assisted selection in wheat breeding practices.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Fenótipo , Triticum/genética , Melhoramento Vegetal , Grão Comestível/genética
3.
Stroke ; 55(5): 1393-1404, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38533660

RESUMO

BACKGROUND: Blood-brain barrier damage has traditionally been considered to determine the occurrence and development of poststroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting blood-brain barrier damage has been proven clinically effective in ameliorating brain edema. METHODS: In mice with stroke models induced by transient middle cerebral artery occlusion (MCAO), the changes in glymphatic system (GS) function impairment were detected by ex vivo fluorescence imaging, 2-photon in vivo imaging, and magnetic resonance imaging within 1 week after MCAO, and the effects of GS impairment and recovery on the formation and resolution of brain edema were evaluated. In addition, in patients with ischemic stroke within 1 week after onset, changes in GS function and brain edema were also observed by magnetic resonance imaging. RESULTS: We found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after MCAO in mice, as brain edema reabsorption preceded blood-brain barrier closure. Strikingly, the time course of edema progression matched well with the GS dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aß (amyloid-ß) and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes. CONCLUSIONS: GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for treating brain edema in ischemic stroke. REGISTRATION: URL: https://www.chictr.org.cn/showproj.html?proj=162857; Unique identifier: NFEC-2019-189.

4.
Asian Biomed (Res Rev News) ; 18(1): 11-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38515630

RESUMO

Background: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China. Objective: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations. Methods: A reverse dot blot assay combined with a flow-through hybridization technique was developed for the simultaneous detection of 13 hotspot mutations of 4 hearing loss-related genes including GJB2, GJB3, SLC26A4, and the mitochondrial gene MT-RNR1. This method involved PCR amplification systems and a hybridization platform. Results: The technique can detect 13 hotspot mutations of 4 hearing loss-related genes. And a total of 213 blood samples were used to evaluate the availability of this method. Discussion: Our reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify hotspot mutations of 4 hearing loss-related genes in a Chinese population.

5.
Abdom Radiol (NY) ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526596

RESUMO

PURPOSE: To explore the diagnostic value of dual-source computed tomography (DSCT) and neutrophil to lymphocyte ratio (NLR) for differentiating gastric signet ring cell carcinoma (SRC) from mixed SRC (mSRC) and non-SRC (nSRC). METHODS: This retrospective study included patients with gastric adenocarcinoma who underwent DSCT between August 2019 and June 2021 at our Hospital. The iodine concentration in the venous phase (ICvp), standardized iodine concentration (NICVP), and the slope of the energy spectrum curve (kVP) were extracted from DSCT data. NLR was determined from laboratory results. DSCT (including ICVP, NICVP, and kVP) and combination (including DSCT model and NLR) models were established based on the multinomial logistic regression analysis. The receiver operator characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic value. RESULTS: A total of 155 patients (SRC [n = 45, aged 61.22 ± 11.4 years], mSRC [n = 60, aged 61.09 ± 12.7 years], and nSRC [n = 50, aged 67.66 ± 8.76 years]) were included. There were significant differences in NLR, ICVP, NICVP, and kVP among the SRC, mSRC, and nSRC groups (all P < 0.001). The AUC of the combination model for SRC vs. mSRC + nSRC was 0.964 (95% CI: 0.923-1.000), with a sensitivity of 98.3% and a specificity of 86.7%, higher than with DSCT (AUC: 0.959, 95% CI: 0.919-0.998, sensitivity: 90.0%, specificity: 89.9%) or NLR (AUC: 0.670, 95% CI: 0.577-0.768, sensitivity: 62.2%, specificity: 61.8%). CONCLUSION: DSCT combined with NLR showed high diagnostic efficacy in differentiating SRC from mSRC and nSRC.

6.
Theor Appl Genet ; 137(3): 58, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407646

RESUMO

KEY MESSAGE: SNP-based and InDel-based GWAS on multi-environment data identified genomic regions associated with barley grain size. Barley yield and quality are greatly influenced by grain size. Improving barley grain size in breeding programs requires knowledge of genetic loci and alleles in germplasm resources. In this study, a collection of 334 worldwide two-rowed barley accessions with extensive genetic diversity was evaluated for grain size including grain length (GL), grain width (GW), and thousand-grain weight (TGW) across six independent field trials. Significant differences were observed in genotype and environments for all measured traits. SNP- and InDel-based GWAS were applied to dissect the genetic architecture of grain size with an SLAF-seq strategy. Two approaches using the FarmCPU model revealed 38 significant marker-trait associations (MTAs) with PVE ranging from 0.01% to 20.68%. Among these MTAs, five were on genomic regions where no previously reported QTL for grain size. Superior alleles of TGW-associated SNP233060 and GL-associated InDel11006 exhibited significantly higher levels of phenotype. The significant MTAs could be used in marker-assisted selection breeding.


Assuntos
Hordeum , Hordeum/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Alelos , Grão Comestível/genética
7.
FASEB J ; 38(4): e23490, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38363581

RESUMO

Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.


Assuntos
Diabetes Mellitus , Células Secretoras de Insulina , Camundongos , Animais , Secreção de Insulina , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Cálcio/metabolismo , Etanol , Insulina/metabolismo
8.
Mol Metab ; 80: 101885, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38246588

RESUMO

OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.


Assuntos
Insulina , Lisina , Camundongos , Animais , Secreção de Insulina , Lisina/metabolismo , Insulina/metabolismo , Glucose/farmacologia , Trifosfato de Adenosina/metabolismo
9.
Taiwan J Obstet Gynecol ; 63(1): 46-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38216268

RESUMO

OBJECTIVE: Despite continuous progress in treatment, recurrence and metastasis limit further improvement in the prognosis of breast cancer (BC) patients. Our aim was to search for a crucial prognostic biomarker of BC. MATERIALS AND METHODS: Patient data were selected from The Cancer Genome Atlas (TCGA) and GTEx databases. Several online public databases, including Gene Expression Profiling Interactive Analysis (GEPIA), miRWalk, miRDB, and LncBase Predicted v.2, were used to identify potential upstream miRNAs and lncRNAs. These findings were validated through in vitro experiments. RESULTS: A total of 1, 097 invasive BC samples and 572 normal breast tissues (including 113 samples from TCGA and 459 samples from GTEx) were collected for the study. CCT4 was not only significantly overexpressed in BC compared with normal breast tissues but also had important prognostic significance (P < 0.001). By intersecting miRWalk and miRDB and conducting correlation analysis, hsa-miR-30c-2-3p was identified as the most probable upstream miRNA of CCT4. Following an extensive assessment that included survival analysis, correlation analysis, and common binding-site prediction, LINC01234 was chosen as the most likely upstream lncRNA. In vitro experiments showed that LINC01234-siRNA inhibited the proliferation, invasion, and migration abilities of BC cells. Western blot analysis further confirmed that LINC01234 promoted malignant behaviors of BC cells via the CCT4/mTOR signaling pathway. CONCLUSION: The LINC01234/hsa-miR-30c-2-3p/CCT4/mTOR axis was identified as a potential ceRNA regulatory mechanism in BC. These findings established the foundation for systematically unveiling the pathological mechanisms of BC and provided new insights for targeted therapy of BC patients.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , MicroRNAs/genética , Prognóstico , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , Chaperonina com TCP-1/genética , Chaperonina com TCP-1/metabolismo
10.
Mol Genet Genomic Med ; 12(1): e2338, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38083988

RESUMO

BACKGROUND: Developmental and epileptic encephalopathy 9 (DEE9) is characterized by early infantile seizures and mild-to-severe neuropsychiatric symptoms. Despite being an X-linked dominant disorder, DEE9 mainly affects heterozygous females or mosaic males, while hemizygous males are less affected. PCDH19 gene has been documented as the causative gene. METHODS: Karyotyping analysis and copy number variation sequencing (CNV-seq) were performed on a pregnant woman with epilepsy, together with her husband, son, and fetus. RESULTS: A disease-causing microdeletion, seq[GRCh37] del(X)(q21.31q22.1) (90310001-100360000), was identified in the pregnant woman and her female fetus. The microdeletion includes the entire PCDH19 gene and is classified as "pathogenic" according to the American College of Medical Genetics and Genomics guidelines. CONCLUSION: In this case study, we have not only identified the epilepsy type of the woman as DEE9 but have also made an unfavorable prognosis for her fetus. Our findings from this prenatal case provide valuable clinical resources for prenatal diagnosis and genetic counseling, while also implying the potential of CNV-seq as a viable method for uncovering PCDH19-related epilepsy.


Assuntos
Epilepsia Generalizada , Feminino , Humanos , Gravidez , Variações do Número de Cópias de DNA , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/genética , Mães , Mutação , Diagnóstico Pré-Natal , Protocaderinas
11.
Am J Cancer Res ; 13(11): 5065-5081, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058820

RESUMO

There is no strong evidence indicating the optimal treatment for breast cancer (BC) and no specific prognostic model. The aim of this study was to establish nomograms to predict the overall survival (OS) of BC patients receiving chemoradiotherapy and surgery, thereby quantifying survival benefits and improving patient management. A total of 1877 patients with primary nonmetastatic BC who received chemoradiotherapy and surgery from 2010 to 2019 were identified from the Surveillance, Epidemiology and End Results (SEER) database as the training cohort, 804 as the internal validation cohort, and 796 patients from the First Affiliated Hospital of Zhengzhou University (n=324) and Jiaxing Maternal and Child Health Hospital (n=472) as the external validation cohort. Least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analyses were performed in the training cohort to determine independent prognostic factors for BC, and a nomogram was constructed to predict 3-year, 5-year, and 8-year OS. The final model incorporated 7 factors that significantly affect OS: race, location, positive regional nodes, T stage, N stage, subtype, and grade. The calibration curves showed good consistency between the predicted survival and actual outcomes. Time-dependent receiver operating characteristic (ROC) curves and the time-dependent area under the curve (AUC) confirmed that the accuracy and clinical usefulness of the constructed nomograms were favorable. Decision curve analysis (DCA) and net reclassification improvement (NRI) also demonstrated that this nomogram was more suitable for clinical use than the 7th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system and the previous prediction model. In the training cohort and the internal validation cohort, the concordance indices (C-index) of the nomogram for predicting OS (0.723 and 0.649, respectively) were greater than those of the 7th AJCC TNM staging system and the previous prediction model. In addition, based on Kaplan-Meier (K-M) survival curves, the survival differences among different risk stratifications were statistically significant, indicating that our risk model was accurate. In this study, we determined independent prognostic factors for OS in patients with primary nonmetastatic BC treated with chemoradiotherapy and surgery. A new and accurate nomogram for predicting 3-, 5-, and 8-year OS in this patient population was developed and validated for potential clinical applicability.

12.
Cancer ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37916832

RESUMO

INTRODUCTION: Breast cancer is a significant contributor to female mortality, exerting a public health burden worldwide, especially in China, where risk-prediction models with good discriminating accuracy for breast cancer are still scarce. METHODS: A multicenter screening cohort study was conducted as part of the Cancer Screening Program in Urban China. Dwellers aged 40-74 years were recruited between 2014 and 2019 and prospectively followed up until June 30, 2021. The entire data set was divided by year of enrollment to develop a prediction model and validate it internally. Multivariate Cox regression was used to ascertain predictors and develop a risk-prediction model. Model performance at 1, 3, and 5 years was evaluated using the area under the curve, nomogram, and calibration curves and subsequently validated internally. The prediction model incorporates selected factors that are assigned appropriate weights to establish a risk-scoring algorithm. Guided by the risk score, participants were categorized into low-, medium-, and high-risk groups for breast cancer. The cutoff values were chosen using X-tile plots. Sensitivity analysis was conducted by categorizing breast cancer risk into the low- and high-risk groups. A decision curve analysis was used to assess the clinical utility of the model. RESULTS: Of the 70,520 women enrolled, 447 were diagnosed with breast cancer (median follow-up, 6.43 [interquartile range, 3.99-7.12] years). The final prediction model included age and education level (high, hazard ratio [HR], 2.01 [95% CI, 1.31-3.09]), menopausal age (≥50 years, 1.34 [1.03-1.75]), previous benign breast disease (1.42 [1.09-1.83]), and reproductive surgery (1.28 [0.97-1.69]). The 1-year area under the curve was 0.607 in the development set and 0.643 in the validation set. Moderate predictive discrimination and satisfactory calibration were observed for the validation set. The risk predictions demonstrated statistically significant differences between the low-, medium-, and high-risk groups (p < .001). Compared with the low-risk group, women in the high- and medium-risk groups posed a 2.17-fold and 1.62-fold elevated risk of breast cancer, respectively. Similar results were obtained in the sensitivity analyses. A web-based calculator was developed to estimate risk stratification for women. CONCLUSIONS: This study developed and internally validated a risk-adapted and user-friendly risk-prediction model by incorporating easily accessible variables and female factors. The personalized model demonstrated reliable calibration and moderate discriminative ability. Risk-stratified screening strategies contribute to precisely distinguishing high-risk individuals from asymptomatic individuals and prioritizing breast cancer screening. PLAIN LANGUAGE SUMMARY: Breast cancer remains a burden in China. To enhance breast cancer screening, we need to incorporate population stratification in screening. Accurate risk-prediction models for breast cancer remain scarce in China. We established and validated a risk-adapted and user-friendly risk-prediction model by incorporating routinely available variables along with female factors. Using this risk-stratified model helps accurately identify high-risk individuals, which is of significant importance when considering integrating individual risk assessments into mass screening programs for breast cancer. Current clinical breast cancer screening lacks a constructive clinical pathway and guiding recommendations. Our findings can better guide clinicians and health care providers.

13.
Explore (NY) ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38007308

RESUMO

OBJECTIVE: To study whether perioperative electroacupuncture (EA) can improve postoperative gastrointestinal recovery in patients receiving thoracoscopic lung surgery. METHODS: This study was a single-center, prospective, randomized open-label trial. 180 patients who underwent video-assisted thoracoscopic segmentectomy or lobectomy were randomized to EA group (three sessions, 24 h prior to surgery, postoperative 4 h and 24 h) or usual care group (UC group). The primary outcomes were time to first flatus and defecation. Secondary outcomes included incidence and degree of abdominal distention, postoperative nausea and vomiting (PONV) and pain scores within 72 h after surgery, postoperative morphine use, time to ambulation, and length of hospital stay. RESULTS: Time to first flatus (15.4 ± 3.2 h vs. 17.0 ± 3.7 h, P = 0.004) and time to first defecation (75.9 ± 7.9 vs. 79.7 ± 8.1 h, P = 0.002) in the EA group were significantly shorter than the UC group. The incidences of abdominal distension and PONV postoperative 24 h were significantly reduced in the EA group (P < 0.05). There was no difference in postoperative pain intensity, morphine use, time to ambulation, and length of hospital stay between the two groups (P>0.05). CONCLUSION: Electroacupuncture is a simple intervention for accelerating postoperative gastrointestinal recovery and may be considered as an adjunct strategy in enhanced recovery protocols in thoracoscopic lung surgery.

14.
Front Endocrinol (Lausanne) ; 14: 1217613, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745721

RESUMO

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma. Methods: Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed. Results: Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD. Conclusion: In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Metástase Linfática , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia
15.
Bull Entomol Res ; 113(5): 665-675, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37555240

RESUMO

Environment-induced epigenetics are involved in diapause regulation, but the molecular mechanism that epigenetically couples nutrient metabolism to diapause regulation remains unclear. In this study, we paid special attention to the significant differences in the level of N6-adenosine methylation (m6A) of dihydroxyacetone phosphate acyltransferase (DHAPAT) and phosphatidate phosphatase (PAP) genes in the lipid metabolism pathway of the bivoltine silkworm (Bombyx mori) strain Qiufeng developed from eggs incubated at a normal temperature (QFHT, diapause egg producer) compared to those from eggs incubated at a low temperature (QFLT, non-diapause egg producer). We knocked down DHAPAT in the pupal stage of the QFLT group, resulting in the non-diapause destined eggs becoming diapausing eggs. In the PAP knockdown group, the colour of the non-diapause destined eggs changed from light yellow to pink 3 days after oviposition, but they hatched as normal. Moreover, we validated that YTHDF3 binds to m6A-modified DHAPAT and PAP mRNAs to promote their stability and translation. These results suggest that RNA m6A methylation participates in the diapause regulation of silkworm by changing the expression levels of DHAPAT and PAP and reveal that m6A epigenetic modification can be combined with a lipid metabolism signal pathway to participate in the regulation of insect diapause traits, which provides a clearer image for exploring the physiological basis of insect diapause.


Assuntos
Bombyx , Diapausa de Inseto , Diapausa , Feminino , Animais , Bombyx/genética , Diapausa de Inseto/genética , Fosfatidato Fosfatase/metabolismo , RNA/metabolismo , Metabolismo dos Lipídeos , Adenosina/metabolismo , Óvulo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
16.
J Affect Disord ; 340: 802-811, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37597777

RESUMO

BACKGROUND: The previous studies an association between dietary patterns and psychiatric symptoms. However, few studies have examined the association of quality of dietary patterns and anxiety, depressive symptoms in the Chinese population. METHODS: Between 2017 and 2019, a population-based, cross-sectional survey was carried out in China. Uniformed questionnaires collected the demographic characteristics and food data. The dietary quality of the adults was evaluated using the revised Diet Balance Index 2016 (DBI-16). We measured anxiety and depression symptoms using the the Generalized Anxiety Disorder (GAD)-7 and Patient Health Questionnaire (PHQ)-9. RESULTS: A total of 73,737 participants were recruited during the survey period. 17.6 % and 13.7 % of residents suffer from anxiety and depression symptoms, respectively. The DBI-16 indicates that participants with anxiety or depression symptoms had higher scores of low bound score (LBS, refers to inadequate food intake) and dietary quality distance (DQD, refers to unbalanced food intake) than those without anxiety or depression. The logistic regression models showed that high levels of LBS and DQD problems were more strongly associated with anxiety (LBS:OR = 1.20, DQD:OR = 1.30) and depressive symptoms (LBS:OR = 1.21, DQD:OR = 1.44). On the contrary, higher bound score (HBS, refers to excessive food intake) was significantly negatively correlated with symptoms of anxiety and depression. Moreover, each increase in the food group was associated with 4 % lower odds of anxiety and 6 % lower odds of depression symptoms. LIMITATIONS: Cross-sectional design and self-reporting of psychological symptoms and dietary information limit the generalizability of the results. CONCLUSION: The dietary quality of adults aged 40 years and over in China is suboptimal, with excessive and inadequate food intake simultaneously. Dietary imbalance, and low dietary diversity may be related to anxiety and depressive symptoms.


Assuntos
Transtornos de Ansiedade , Ansiedade , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Dieta , China/epidemiologia
17.
Gene ; 881: 147626, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37423399

RESUMO

Diapause of the silkworm (Bombyx mori) is an important ecological adaptation strategy regulated by multiple signaling pathways. As an evolutionarily conserved signaling pathway, the insulin/IGF signaling (IIS) pathway is essential in regulating lifespan, energy accumulation, and stress resistance in diapause insects. However, the regulatory mechanism of IIS on diapause in B. mori is still not fully understood. To investigate the role of the IIS pathway in regulating diapause, we first analyzed the transcription levels of the insulin receptor (BmINR) and its downstream gene adenylate cyclase 6 (BmAC6). The diapause-terminated eggs of a bivoltine strain QiuFeng (V2-QF) were incubated at 25 °C in natural room light for preparing diapause egg producers (DEPs) and at 17 °C in total darkness for preparing non-diapause egg producers (NDEPs), respectively. Then we investigated the effects of BmINR and BmAC6 on diapause phenotype and expression of diapause-related genes by RNA interference (RNAi) and overexpression techniques. The results showed that the mRNA expression levels of BmINR and BmAC6 in the head and ovary of NDEPs were higher than those in DEPs during the early and middle pupal stages. Furthermore, when BmINR was knocked down in the NDEPs, approximately 14.43% of eggs were in light red color and subsequently changed into gray-purple color after 48 h post-oviposition, then stayed in a diapause state. On the other hand, overexpression of BmINR or BmAC6 via recombinant baculoviruses did not cause any obvious phenotypic alterations in NDEPs, but it upregulated the expression of genes related to carbohydrate metabolism, which provides energy for embryonic growth and development. Therefore, it can be concluded that BmINR and BmAC6 genes regulate embryonic diapause in bivoltine B. mori.


Assuntos
Bombyx , Animais , Feminino , Insulina/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Transdução de Sinais , Pupa/genética , Pupa/metabolismo , Óvulo/metabolismo
18.
Int Immunopharmacol ; 122: 110660, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37478665

RESUMO

JAK kinase includes four family members: JAK1, JAK2, JAK3, and TYK2. It forms the JAK-STAT pathway with signal transmitters and activators of subscription (STAT). This pathway is one of the main mechanisms by which many cytokine receptors transduce intracellular signals, it is associated with the occurrence of various immune, inflammatory, and tumor diseases. JAK inhibitors block the signal transduction of the JAK-STAT pathway by targeting JAK kinase. Based on whether they target multiple subtypes of JAK kinase, JAK inhibitors are categorized into pan-JAK inhibitors and selective JAK inhibitors. Compared with pan JAK inhibitors, selective JAK inhibitors are associated with a specific member, thus more targeted in therapy, with improved efficacy and reduced side effects. Currently, a number of JAK inhibitors have been approval for disease treatment. This review summarized the current application status of JAK inhibitors that have been marketed, advances of JAK inhibitors currently in phase Ш clinical trials, and the structure-activity relationship of them, with an intention to provide references for the development of novel JAK inhibitors.


Assuntos
Inibidores de Janus Quinases , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
19.
J Assist Reprod Genet ; 40(9): 2219-2231, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37480419

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies. METHOD: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth. RESULTS: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period. CONCLUSION: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors.


Assuntos
Síndrome de Down , Teste Pré-Natal não Invasivo , Gravidez , Feminino , Humanos , Síndrome de Down/diagnóstico , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Trissomia/diagnóstico , Trissomia/genética , Variações do Número de Cópias de DNA/genética , Gravidez de Gêmeos/genética , Aberrações Cromossômicas , Aneuploidia , China/epidemiologia
20.
Eur J Pharmacol ; 955: 175933, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481199

RESUMO

Ketogenic diet (KD) is a classical nonpharmacological therapy that has recently been shown to benefit cerebral ischemia, but the mechanism remains unclear. This study investigated the neuroprotective effects of KD pretreatment and ß-hydroxybutyrate (BHB, bioactive product of KD) post-treatment in a mouse model of temporary middle cerebral artery occlusion (tMCAO). Neurological function, infarct volume, as well as inflammatory reactions are evaluated 24 h after ischemia. Results showed that both KD pretreatment or BHB post-treatment improved the Bederson score and Grip test score, reduced infarct volume and the extravasation of IgG, suppressed the over-activation of microglia, and modulated the expression of cytokines. Mechanically, we found that both KD pretreatment or BHB post-treatment significantly stimulated the expression of interleukin-1 receptor-associated kinase M (IRAKM) and then inhibited the nuclear translocation of NF-κB. IRAKM deletion (Irakm-/-) exacerbated tMCAO-induced neurovascular injuries, and aggravated neuroinflammatory response. Moreover, KD pretreatment or BHB post-treatment lost their neuroprotection in the tMCAO-treated Irakm-/- mice. Our results support that KD pretreatment and BHB post-treatment alleviate ischemic brain injury in mice, possibly via an IRAKM-dependent way.

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