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Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demonstrated that the knockdown of EIF4A3 significantly inhibited the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. The findings of mass spectrometry analysis revealed that EIF4A3 could interact with Flotillin-1 in LUAD cells and that EIF4A3 could positively regulate the expression of FLOT1 at the protein level. Meanwhile, transcriptome sequencing showed that EIF4A3 could influence the development of LUAD by affecting PI3K–AKT–ERK1/2–P70S6K and PI3K class III–mediated autophagy in the Apelin pathway. In addition, we confirmed that Flotillin-1 expression was upregulated in LUAD based on the existing literature, and knockdown of FLOT1 could inhibit the proliferation and migration of LUAD cells. In addition, the knockdown of Flotillin-1 reversed the increase of cell proliferation and migration caused by EIF4A3 overexpression. Furthermore, we found that the activation of PI3K–AKT–ERK1/2–P70S6K signaling pathway and PI3K class III–mediated autophagy caused by EIF4A3 overexpression was rescued by the knockdown of FLOT1. In a word, we proved that EIF4A3 positively regulates the expression of FLOT1 and plays a procancer role in LUAD. Implications: Our study revealed the role of EIF4A3 in prognosis and tumor progression in LUAD, indicating that EIF4A3 could be used as the molecular diagnostic and prognostic therapeutic target.

Background: Non-small cell lung cancer (NSCLC) is the most common malignancy and one of the most common causes of cancer-related death worldwide. Robotic-assisted thoracic surgery (RATS) has gradually become a prevalent surgical method for patients with NSCLC. Previous studies have found that body mass index (BMI) is associated with postoperative outcomes. This study aimed to investigate the effectiveness of RATS compared to video-assisted thoracic surgery (VATS) in the treatment of NSCLC with different BMI, in terms of perioperative outcomes. Methods: The baseline and perioperative data, including BMI, of 849 NSCLC patients who underwent minimally invasive anatomic lung resections from August 2020 to April 2021 were retrospectively collected and analyzed. Propensity score matching analysis was applied to minimize potential bias between the two groups (VATS and RATS), and the perioperative outcomes were compared. Subgroup analysis was subsequently performed. Results: Compared to VATS, RATS had more lymph nodes dissected {9 [inter-quartile range (IQR), 6-12] vs. 7 (IQR, 6-10), P

BackgroundBladder cancer is the ninth most common malignant tumor worldwide. As an effective evidence-based multidisciplinary protocol, the enhanced recovery after surgery (ERAS) program is practiced in many surgical disciplines. However, the function of ERAS after radical cystectomy remains controversial. This systematic review and meta-analysis aims to research the impact of ERAS on radical cystectomy.MethodsA systematic literature search on PubMed, EMBASE, SCOPUS, and the Cochrane Library databases was conducted in April 2022 to identify the studies that performed the ERAS program in radical cystectomy. Studies were selected, data extraction was performed independently by two reviewers, and quality was assessed using a random effects model to calculate the overall effect size. The odds ratio and standardized mean difference (SMD) with a 95% confidence interval (CI) served as the summary statistics for the meta-analysis. A sensitivity analysis was subsequently performed.ResultsA total of 25 studies with 4,083 patients were enrolled. The meta-analysis showed that the complications (OR = 0.76; 95% CI: 0.63–0.90), transfusion rate (OR = 0.59; 95% CI: 0.39–0.90), readmission rate (OR = 0.79; 95% CI: 0.64–0.96), length of stay (SMD = −0.79; 95% CI: −1.41 to −0.17), and time to first flatus (SMD = −1.16; 95% CI: −1.58 to −0.74) were significantly reduced in the ERAS group. However, no significance was found in 90-day mortality and urine leakage.ConclusionThe ERAS program for radical cystectomy can effectively decrease the risk of overall complications, postoperative ileus, readmission rate, transfusion rate, length of stay, and time to first flatus in patients who underwent radical cystectomy with relative safety.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202250075.

Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demonstrated that the knockdown of EIF4A3 significantly inhibited the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. The findings of mass spectrometry analysis revealed that EIF4A3 could interact with Flotillin-1 in LUAD cells and that EIF4A3 could positively regulate the expression of FLOT1 at the protein level. Meanwhile, transcriptome sequencing showed that EIF4A3 could influence the development of LUAD by affecting PI3K–AKT–ERK1/2–P70S6K and PI3K class III–mediated autophagy in the Apelin pathway. In addition, we confirmed that Flotillin-1 expression was upregulated in LUAD based on the existing literature, and knockdown of FLOT1 could inhibit the proliferation and migration of LUAD cells. In addition, the knockdown of Flotillin-1 reversed the increase of cell proliferation and migration caused by EIF4A3 overexpression. Furthermore, we found that the activation of PI3K–AKT–ERK1/2–P70S6K signaling pathway and PI3K class III–mediated autophagy caused by EIF4A3 overexpression was rescued by the knockdown of FLOT1. In a word, we proved that EIF4A3 positively regulates the expression of FLOT1 and plays a procancer role in LUAD.Implications:Our study revealed the role of EIF4A3 in prognosis and tumor progression in LUAD, indicating that EIF4A3 could be used as the molecular diagnostic and prognostic therapeutic target.

Correlation between EIF4A3 expression and clinicopathological characteristics in LUAD

EIF4A3 promotes the proliferation and migration of LUAD cells in vitro.

Information of antibodies

Sequence of small interfering RNA

The Metaverse depicts a parallel digitalized world where virtuality and reality are fused. It has economic and social systems like those in the real world and provides intelligent services and applications. In this paper, we introduce the Metaverse from a new technology perspective, including its essence, corresponding technical framework, and potential technical challenges. Specifically, we analyze the essence of the Metaverse from its etymology and point out breakthroughs promising to be made in time, space, and contents of the Metaverse by citing Maslow's Hierarchy of Needs. Subsequently, we conclude four pillars of the Metaverse, named ubiquitous connections, space convergence, virtuality and reality interaction, and human-centered communication, and establish a corresponding technical framework. Additionally, we envision open issues and challenges of the Metaverse in the technical aspect. The work proposes a new technology perspective of the Metaverse and will provide further guidance for its technology development in the future.

ObjectiveTo compare the efficacy of flexible ureteroscopy for single urinary stones with that of multiple urinary stones.MethodsA retrospective study was conducted on patients who underwent flexible ureteroscopy in Qilu Hospital of Shandong University from January 2016 to March 2021. Propensity score matching was used to match patients with no statistical difference in preoperative clinical data, and they were divided into solitary calculi and multiple calculi two groups. The postoperative hospital days, operation time, complications and stone free rate were compared between the two groups. And multiple stones were divided into high group (S-ReSc > 4) and non-high group (S-ReSc ≤ 4) for analysis.Results313 patients were counted. After propensity score matching, 198 patients were finally included in the study. There were 99 cases in the solitary stone group and the multiple stone group. There were no significant differences in postoperative hospital days, complications and stone free rate between the two groups. The operation time of patients with solitary stone group was significantly shorter than that of patients with multiple stones (65.00 min, 45.00 min VS 90.00 min, 50.00 min, P P = 0.013).ConclusionDespite the longer operation time, flexible ureteroscopy has similar outcomes in the treatment of multiple (S-Rec ≤ 4) compared to solitary calculi. Although, this doesn't apply when S-ReSc > 4.

Esophageal cancer (EC) is one of the most life-threatening malignancies worldwide. Esophageal squamous cell carcinoma (ESCC) is the dominant subtype, accounting for approximately 90% of new incident EC each year. Although multidisciplinary treatment strategies have advanced rapidly, patients with ESCC are often diagnosed at advanced stage and the long-term prognosis remains unsatisfactory. In recent decades, immunotherapy, such as immune checkpoint inhibitors (ICIs), tumor vaccines, and chimeric antigen receptor T-cell (CAR-T) therapy, has been successfully used in clinical practice as a novel therapy for treating tumors, bringing new hope to ESCC patients. However, only a small fraction of patients achieved clinical benefits due to primary or acquired resistance. Immune evasion plays a pivotal role in the initiation and progression of ESCC. Therefore, a thorough understanding of the mechanisms by which ESCC cells escape from anti-tumor immunity is necessary for a more effective multidisciplinary treatment strategy. It has been widely recognized that immune evasion is closely associated with the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic complex and comprehensive system including not only cellular components but also non-cellular components, which influence hallmarks and fates of tumor cells from the outside. Novel immunotherapy targeting tumor-favorable TME represents a promising strategy to achieve better therapeutic responses for patients with ESCC. In this review, we provide an overview of immune evasion in ESCC, mainly focusing on the molecular mechanisms that underlie the role of TME in immune evasion of ESCC. In addition, we also discuss the challenges and opportunities of precision therapy for ESCC by targeting TME.

Background: N-Alpha-Acetyltransferase 50 (NAA50) has acetyltransferase activity and is important for chromosome segregation. However, the function and mechanism of NAA50 expression in cancer development was still unclear. Here, we systematically researched the function and mechanism of NAA50 in pan-cancer, and further verified the results of NAA50 in lung adenocarcinoma (LUAD).Methods: In this study, using the online databases TIMER2.0, SangerBox3.0, HPA, UCSC, GEPIA, cBioPortal, UALCAN, TISIDB, CancerSEA and LinkedOmics, we focused on the relevance between NAA50 and oncogenesis, progression, methylation, immune infiltration, function and prognosis. In addition, the proliferation of cells was detected by CCK-8 and Edu assay. Finally, we analyzed the relationship between the expression of NAA50 and cell cycle related proteins.Results: Pan-cancer analysis indicated that NAA50 was overexpressed in most cancers. And there was a significant correlation between NAA50 expression and the prognosis of cancer patients. In the meantime, NAA50 gene changes occur in a variety of tumors. Compared with normal tissues, the methylation level of NAA50 promoter increased in most cancer tissues. In addition, the results exhibited that in most cancers, NAA50 was significantly positively correlated with bone myeloid-derived suppressor cell (MDSC) infiltration and negatively correlated with T cell NK infiltration. Moreover, functional enrichment indicated that NAA50 regulates cell cycle and proliferation in LUAD. In vitro experiments testified that knockout of NAA50 could significantly inhibit the proliferation of LUAD.Conclusion: NAA50 may be a potential biomarker and oncogene of pan-cancer, especially LUAD, which may promote the occurrence and development of tumors through different mechanisms. Furthermore, NAA50 was bound up with to immune cell infiltration in pan-cancer, meaning NAA50 may be an important therapeutic target for human cancers.

(1) Background: The study aimed to construct nomograms to improve the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in the Asian population. (2) Methods: This multicenter prospective study included a group of 293 patients from three hospitals. Univariable and multivariable logistic regression analysis was performed to identify potential risk factors and construct nomograms. Discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. The web-based dynamic nomograms were subsequently built based on multivariable logistic analysis. (3) Results: A total of 293 patients were included in our study with 201 negative and 92 positive results in PCa. Four independent predictive factors (age, prostate health index (PHI), prostate volume, and prostate imaging reporting and data system score (PI-RADS)) for PCa were included, and four factors (age, PHI, PI-RADS, and Log PSA Density) for CSPCa were included. The area under the ROC curve (AUC) for PCa was 0.902 in the training cohort and 0.869 in the validation cohort. The AUC for CSPCa was 0.896 in the training cohort and 0.890 in the validation cohort. (4) Conclusions: The combined diagnosis of PHI and PI-RADS can avoid more unnecessary biopsies and improve the detection rate of PCa and CSPCa. The nomogram with the combination of age, PHI, PV, and PI-RADS could improve the detection of PCa, and the nomogram with the combination of age, PHI, PI-RADS, and Log PSAD could improve the detection of CSPCa.

ObjectiveThis study aims to determine the optimal pelvic lymph node dissection (PLND) template for radical cystectomy (RC).MethodsA systematic search was conducted using the PubMed, Embase and Cochrane Library database in December 2021. Articles comparing recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), and postoperative complications among patients undergoing limited PLND (lPLND), standard PLND (sPLND), extended PLND (ePLND), or super-extended PLND (sePLND) were included. A Bayesian approach was used for network meta-analysis.ResultsWe included 18 studies in this systematic review, and 17 studies met our criteria for network meta-analysis. We performed meta-analyses and network meta-analyses to investigate the associations between four PLND templates and the RFS, DSS, OS, or postoperative complications. We found that the ePLND group and the sePLND group were associated with better RFS than the sPLND group (Hazard Ratio [HR]: 0.65, 95% Credible Interval [CrI]: 0.56 to 0.78) (HR: 0.67, 95% CrI: 0.56 to 0.83) and the lPLND group (HR: 0.67, 95% CrI: 0.50 to 0.91) (HR: 0.70, 95% CrI: 0.49 to 0.99). For RFS, Analysis of the treatment ranking revealed that ePLND had the highest probabilities to be the best template. There was no significant difference between the four templates in DSS, however, analysis of the treatment ranking indicated that sePLND had the highest probabilities to be the best template. And We found that the sePLND group and the ePLND group were associated with better OS than lPLND (HR: 0.58, 95% CrI: 0.36 to 0.95) (HR: 0.63, 95% CrI: 0.41 to 0.94). For OS, analysis of the treatment ranking revealed that sePLND had the highest probabilities to be the best template. The results of meta-analyses and network meta-analyses showed that postoperative complications rates did not differ significantly between any two templates.ConclusionPatients undergoing sePLND and ePLND had better RFS but not better DSS or OS than those undergoing lPLND or sPLND templates, however, RFS did not differ between patients undergoing sePLND or ePLND. Considering that sePLND involves longer operation time, higher risk, and greater degree of difficulty than ePLND, and performing sePLND may not result in better prognosis, so it seems that there is no need for seLPND. We think that ePLND might be the optimal PLND template for RC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022318475.

BackgroundA novel inflammatory marker called the systemic immune-inflammation index (SII) was applied to predict the prognosis of different cancers. However, the role of SII in prostate cancer (PCa) remains unclear. This systematic review aims to explore the prognostic role of SII in different stage PCa.MethodsWe comprehensively searched three public databases: PubMed, EMBASE, and the Cochrane Library. The hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted to evaluate the association between SII and the prognosis and clinicopathological characteristics in different stage PCa patients.ResultsTen studies and 7,986 patients were enrolled in our meta-analysis, 1,442 patients were diagnosed with metastatic-castration resistant prostate cancer (mCRPC), and 6544 patients were diagnosed with non-metastatic prostate cancer (nmPCa). According to the pooled results, we found that a high SII was associated with worse overall survival (OS) in mCRPC patients (HR = 1.94, 95% CI: 1.26–3.01, p = 0.003), and a high SII was associated with biochemical recurrence-free survival (BFS) in nmPCa patients (HR = 1.85, 95% CI: 1.06–3.24, p = 0.031). But there was no significant association observed between SII and progression-free survival (PFS) in mCRPC patients (HR = 1.90, 95% CI: 0.87–4.14, p = 0.107). And we found that the high SII was associated with advanced tumor stage of PCa (OR = 2.19, 95% CI: 1.11–4.33, p = 0.024), presence of lymph node involvement (OR = 2.72, 95% CI: 1.96–3.76, p < 0.001) and Gleason score (OR = 1.27, 95% CI: 1.13–1.44, p < 0.001).ConclusionHigh SII was associated with bad OS in mCRPC patients, and associated with bad BFS and some adverse pathological features in nmPCa patients. We think SII can be a prognostic predictor for PCa patients. The application of SII will advance the diagnosis and treatment of different stage prostate cancer.

An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of electromagnetic navigation bronchoscopy (ENB)-guided thoracoscopic sublobectomy for stage IA SMPLC.Patients with SMPLC who underwent ENB-guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted.Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7 cm (range from 0.5 to 1.1 cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p 0.01) and negatively correlated with the distance from the nodule to the pleura (p = 0.02). All nodules were completely resected. Operation time, drainage volume on the third postoperative day, and catheter time were significantly correlated with the resected lesion numbers (p = 0.009, p = 0.004, and p = 0.01, respectively).ENB-guided uniportal video-assisted thoracoscopic sublobectomy provides accurate preoperative localization and avoids unnecessary lung resection of patients with stage IA SMPLC. However, complete resection of multilocation nodules (more than four lesions) increases the risk of postoperative complications. A new combined treatment strategy for SMPLC should be explored.

Emerging studies have indicated that long non-coding RNAs (lncRNAs) play important roles in skeletal muscle growth and development. Nevertheless, it remains challenging to understand the function and regulatory mechanisms of these lncRNAs in muscle biology and associated diseases. Here, we identify a novel lncRNA, Mir22hg, that is significantly upregulated during myoblast differentiation and is highly expressed in skeletal muscle. We validated that Mir22hg promotes myoblast differentiation in vitro. Mechanistically, Mir22hg gives rise to mature microRNA (miR)-22-3p, which inhibits its target gene, histone deacetylase 4 (HDAC4), thereby increasing the downstream myocyte enhancer factor 2C (MEF2C) and ultimately promoting myoblast differentiation. Furthermore, in vivo, we documented that Mir22hg knockdown delays repair and regeneration following skeletal muscle injury and further causes a significant decrease in weight following repair of an injured tibialis anterior muscle. Additionally, Mir22hg gives rise to miR-22-3p to restrict HDAC4 expression, thereby promoting the differentiation and regeneration of skeletal muscle. Given the conservation of Mir22hg between mice and humans, Mir22hg might constitute a promising new therapeutic target for skeletal muscle injury, skeletal muscle atrophy, as well as other skeletal muscle diseases.

BackgroundIn recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes.MethodsA comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.ResultsA total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14–2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48–2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized.ConclusionsThis meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

The alteration in skeletal muscle fiber is a critical factor affecting livestock meat quality traits and human metabolic diseases. Long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs with a length of more than 200 nucleotides. However, the mechanisms underlying the regulation of lncRNAs in skeletal muscle fibers remain elusive. To understand the genetic basis of lncRNA-regulated skeletal muscle fiber development, we performed a transcriptome analysis to identify the key lncRNAs affecting skeletal muscle fiber and meat quality traits on a pig model. We generated the lncRNA expression profiles of fast-twitch Biceps femoris (Bf) and slow-twitch Soleus (Sol) muscles and identified the differentially expressed (DE) lncRNAs using RNA-seq and performed bioinformatics analyses. This allowed us to identify 4581 lncRNA genes among six RNA libraries and 92 DE lncRNAs between Bf and Sol which are the key candidates for the conversion of skeletal muscle fiber types. Moreover, we detected the expression patterns of lncRNA MSTRG.42019 in different tissues and skeletal muscles of various development stages. In addition, we performed a correlation analyses between the expression of DE lncRNA MSTRG.42019 and meat quality traits. Notably, we found that DE lncRNA MSTRG.42019 was highly expressed in skeletal muscle and its expression was significantly higher in Sol than in Bf, with a positive correlation with the expression of Myosin heavy chain 7 (MYH7) (r = 0.6597, p = 0.0016) and a negative correlation with meat quality traits glycolytic potential (r = &minus, 0.5447, p = 0.0130), as well as drip loss (r = &minus, 0.5085, p = 0.0221). Moreover, we constructed the lncRNA MSTRG.42019&ndash, mRNAs regulatory network for a better understanding of a possible mechanism regulating skeletal muscle fiber formation. Our data provide the groundwork for studying the lncRNA regulatory mechanisms of skeletal muscle fiber conversion, and given the importance of skeletal muscle fiber types in muscle-related diseases, our data may provide insight into the treatment of muscular diseases in humans.

Background Prolonged air leak (PAL) remains one of the most frequent postoperative complications after pulmonary resection. This study aimed to develop a predictive nomogram to estimate the risk of PAL for individual patients after minimally invasive pulmonary resection. Methods Patients who underwent minimally invasive pulmonary resection for either benign or malignant lung tumors between January 2020 and December 2021 were included. All eligible patients were randomly assigned to the training cohort or validation cohort at a 3:1 ratio. Univariate and multivariate logistic regression were performed to identify independent risk factors. All independent risk factors were incorporated to establish a predictive model and nomogram, and a web-based dynamic nomogram was then built based on the logistic regression model. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve. The calibration power was evaluated using the Hosmer-Lemeshow test and calibration curves. The nomogram was also evaluated for clinical utility by the decision curve analysis (DCA). Results A total of 2213 patients were finally enrolled in this study, among whom, 341 cases (15.4%) were confirmed to have PAL. The following eight independent risk factors were identified through logistic regression: age, body mass index (BMI), smoking history, percentage of the predicted value for forced expiratory volume in 1 second (FEV1% predicted), surgical procedure, surgical range, operation side, operation duration. The area under the ROC curve (AUC) was 0.7315 [95% confidence interval (CI): 0.6979–0.7651] for the training cohort and 0.7325 (95% CI: 0.6743–0.7906) for the validation cohort. The P values of the Hosmer-Lemeshow test were 0.388 and 0.577 for the training and validation cohorts, respectively, with well-fitted calibration curves. The DCA demonstrated that the nomogram was clinically useful. An operation interface on a web page (https://lirongyangql.shinyapps.io/PAL_DynNom/) was built to improve the clinical utility of the nomogram. Conclusion The nomogram achieved good predictive performance for PAL after minimally invasive pulmonary resection. Patients at high risk of PAL could be identified using this nomogram, and thus some preventive measures could be adopted in advance.

BackgroundWith the widespread adoption of prostatic-specific antigen (PSA) screening, the detection rates of prostate cancer (PCa) have increased. Due to the low specificity and high false-positive rate of serum PSA levels, it was difficult to diagnose PCa accurately. To improve the diagnosis of PCa and clinically significant prostate cancer (CSPCa), we established novel models on the basis of the prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) in the Asian population.MethodsWe retrospectively collected the clinical indicators of patients with TPSA at 4–20 ng/ml. Furthermore, mpMRI was performed using a 3.0-T scanner and reported in the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS). Univariable and multivariable logistic analyses were performed to construct the models. The performance of different models based on PSA derivatives, PHI derivatives, PI-RADS, and a combination of PHI derivatives and PI-RADS was evaluated.ResultsAmong the 128 patients, 47 (36.72%) patients were diagnosed with CSPCa and 81 (63.28%) patients were diagnosed with non-CSPCa. Of the 81 (63.28%) patients, 8 (6.25%) patients were diagnosed with Gleason Grade 1 PCa and 73 (57.03%) patients were diagnosed with non-PCa. In the analysis of the receiver operator characteristic (ROC) curves in TPSA 4–20 ng/ml, the multivariable model for PCa was significantly larger than that for the model based on the PI-RADS (p = 0.004) and that for the model based on the PHI derivatives (p = 0.031) in diagnostic accuracy. The multivariable model for CSPCa was significantly larger than that for the model based on the PI-RADS (p = 0.003) and was non-significantly larger than that for the model based on the PHI derivatives (p = 0.061) in diagnostic accuracy. For PCa in TPSA 4–20 ng/ml, a multivariable model achieved the optimal diagnostic value at four levels of predictive variables. For CSPCa in TPSA 4–20 ng/ml, the multivariable model achieved the optimal diagnostic value at a sensitivity close to 90% and 80%.ConclusionsThe models combining PHI derivatives and PI-RADS performed better in detecting PCa and CSPCa than the models based on either PHI or PI-RADS.

The effectiveness of robotic-assisted lobectomy (RAL) for patients with non-small-cell lung cancer (NSCLC) has not been fully evaluated.This retrospective study compared the perioperative outcomes of NSCLC patients who underwent RAL and video-assisted lobectomy (VAL) using propensity score matching (PSM) analysis. Subgroup analyses were then performed.A total of 822 NSCLC patients (359 RAL cases and 463 VAL cases) were included, and there were 292 patients in each group after PSM. Compared with the VAL group, the RAL group had a significantly higher number of lymph nodes (LNs) harvested (10 vs. 8, p 0.001) and more LN stations examined (6 vs. 5, p 0.001). The operative duration (95 minutes vs. 115 minutes, p 0.001) and intraoperative estimated blood loss (65 mL vs. 80 mL, p 0.001) were significantly reduced, and the drainage volume on postoperative day (POD) 1 (240 mL vs. 200 mL, p 0.001) and hospitalization costs (¥81084.96 vs. ¥66142.55, p 0.001) were significantly higher in the RAL group. Subgroup analysis indicated that the incidence of postoperative complications (17.9% vs. 26.7%, p = 0.042) was significantly reduced in the RAL group for overweight and obese patients (body mass index [BMI] ≥24 kg/mRAL might have potential advantages in terms of lymph node assessment, reducing intraoperative blood loss, and shortening operation duration. Overweight and obese patients could benefit more from RAL because of reduced risk of postoperative complications.

In mammals, a vast majority of ovarian follicles undergo atresia, which is caused by granulosa cell (GC) apoptosis. GCs in follicles are exposed to low oxygen. Hypoxia triggers reactive oxygen species (ROS) generation, which leads to cell oxidative stress and apoptosis. Sulforaphane (SFN), a phytochemical isothiocyanate enriched in cruciferous vegetables, has exhibited a crucial role in mitigating oxidative stress. To explore the effect of SFN on porcine GC apoptosis in a hypoxic environment, we handled the established hypoxia model (1% O

Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and ob/ob mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of Cidec. Consistently, overexpression of Cidec in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of Cidec through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of Cidec via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.

Review question / Objective: We intend to perform a systematic review and meta-analysis to further identify the safety and feasibility of the non-routine chest tube drainage strategy after video-assisted thoracoscopic pulmonary resection. Condition being studied: Comparison of perioperative outcomes between with and without routine chest tube drainage after video-assisted thoracoscopic pulmonary resection. Information sources: Electronic databases : Pubmed, EMBASE and Cochrane Library. We also manually searched the reference lists of excluded publications to identify any further potential nonduplicate studies.

Although many long non-coding RNAs (lncRNAs) have been identified in muscle, some of their physiological functions and regulatory mechanisms remain elusive. Here we report the functional identification and characterization of a novel lncRNA 2310043L19Rik (lnc-231), which is highly expressed in muscle. The expression level of lnc-231 in skeletal muscle of young mice is higher than that in aged mice. Functional analysis showed that overexpression of lnc-231 restrained differentiation and promoted proliferation of myoblast, while inhibition of lnc-231 revealed completely opposite effects in vitro. RNA molecules of lnc-231 acted mechanistically as competing endogenous RNAs (ceRNA) to target miR-125a-5p, whereas miR-125a-5p binds to the 3’-UTR of E2F3 mRNA to inhibit its function. Collectively, lncRNA 2310043L19Rik promotes proliferation and inhibits differentiation of myoblast cells by attenuating the function of miR-125a-5p.

Dementia is a severe disease threatening ageing societies, which not only causes great harm to patients both physically and psychologically but also places a heavy burden on patients’ families. Medications have been used for the treatment of dementia but with little success. However, serious games, as a new form of dementia therapy, stand out from various therapeutic methods and pave the way for dementia treatment. In the field of serious games for dementia care (SGDC) in ageing societies, there exists abundant research related to this topic. While, a detailed review of the development route and a category framework for characteristics of dementia are still needed. Besides, due to the large number of games, it is difficult to select out effective ones. Yet, there is no unified and comprehensive assessment methods for SGDC. So a reliable assessment model is worth studying. In this paper, we review these existing research work on SGDC from two perspectives: (1) the development of SGDC; (2) the different symptoms in different dementia stages. We also propose a comprehensive and professional assessment model of the therapeutic effectiveness of SGDC to compensate for the simplicity of existing assessment methods. Finally, a discussion related to SGDC is presented., We review the existing research on Serious Games for Dementia Care (SGDC) from two perspectives: (1) the development of SGDC; (2) the different symptoms in different dementia stages. We also propose and discuss a comprehensive and professional assessment model of the therapeutic effectiveness of SGDC to compensate for the simplicity of existing assessment methods.

Children's non-neurogenic voiding dysfunction (NVD) is a syndrome characterized by lower urinary tract symptoms (LUTs) because of the inability to relax the external sphincter. Patients with NVD always suffer from urinary tract infections (UTI), incontinence, constipation. The aim of this study is to assess the efficacy of biofeedback treatment for children's NVD.PubMed, Embase, Cochrane library database were searched for all relevant studies. Two independent reviewers decided whether to include the study, conducted quality evaluation, and extracted article data. A random-effects model was used to calculate overall effect sizes. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. And sensitivity analysis was subsequently performed.Fifteen studies and 1274 patients were included in the systemic review, seven RCTs and 539 patients were included in meta-analysis. Meta-analysis showed efficacy of biofeedback treatment in following aspects, (1) relieving UTI (RR: 1.71, 95% CI: 1.11 to 2.64), (2) reducing PVR (MD: 9.51, 95% CI: 2.03 to 16.98), (3) increasing maximum urine flow rate (MD: 4.28, 95% CI: 2.14 to 6.42) and average urine flow rate (MD: 1.49, 95% CI: 0.53 to 2.46), (4) relieving constipation (RR: 1.59, 95% CI: 1.12 to 2.26)，(5) improving abnormal voiding pattern (RR: 1.75, 95% CI: 1.30 to 2.36) and abnormal EMG during voiding (RR: 1.55, 95% CI: 1.25 to 1.91). The improvement of UTI symptoms, maximum urine flow rate and average urine flow rate took a longer time (12 months). In terms of daytime incontinence (RR: 1.20, 95% CI [0.96, 1.50], p = 0.11), nighttime incontinence (RR: 1.20, 95% CI [0.62, 2.32], p = 0.58), no significant difference was found between biofeedback treatment and standard urotherapy. The qualitative analysis showed that biofeedback treatment was beneficial for NVD.Compared with standard urotherapy, biofeedback treatment is effective for some symptoms, such as UTI and constipation, and can improve some uroflowmetric parameters, such as PVR. Biofeedback treatment seems to have a better long-term effect.

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan–Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive malignancy and accounts for the majority of cancer-related death worldwide. It is often diagnosed at an advanced stage and entails a poor prognosis for those afflicted. The mechanisms of its pathogenesis and progress remain unclear and require urgent elucidation. This study aimed to identify specific genes and potential pathways associated with the progression and prognosis of EAC using bioinformatics analyses. METHODS: EAC microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs) using bioinformatics analysis. The DEGs in TCGA were then analyzed to construct a co-expression network by weighted correlation network analysis (WGCNA), and module-clinical trait relationships were analyzed to explore the genes that associated with clinicopathological parameters of EAC. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed for the cancer-related genes, and a DEG-based protein-protein interaction (PPI) network was used to extract hub genes through Cytoscape plugins. The consensus survival analysis for EAC (OSeac) was performed to identify the prognosis-related genes. The immune infiltration was evaluated by tumor immune estimation resource (TIMER) algorithms, and a risk score prognostic model was established using univariate, multivariate Cox proportional hazards regression, and lasso regression analysis. RESULTS: Ultimately, 190 cancer-related DEGs were identified, 6 of which were found to play vital roles in the progression of EAC, including ACTA2, BGN, CALD1, COL1A1, COL4A1, and DCN. The risk score prognostic model consisted of 6 other genes that had an important impact on the prognosis of EAC, including CLDN3, EPB41L4A, ESM1, MT1X, PAQR5, and PLAU. The area under the curve of the prognostic model for predicting the survival of patients at 1, 2, and 3 years was 0.707, 0.702, and 0.726, respectively. CONCLUSIONS: This study identified several genes with the potential to become useful targets for the diagnosis and treatment of EAC. The 6-gene-related risk score prognostic model and nomogram based on these genes may be a reliable tool for predicting the prognosis of patients with EAC.

Chicken blastodermal cells (BCs) are pluripotent stem cells derived from early embryos and may be easily obtained and manipulated. However, in vitro cultured BCs have extremely low germline capacity, which may limit their applications. Research on the germ cell differentiation of mammalian pluripotent cells using chemical-inducing agents has gained popularity, and tremendous achievements have been made. Whether chemical-inducing agents allow acquirement of germline competence in BCs is, however, questionable. In this study, retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) promoted the expression of germline-specific genes and restored the germline competence of in vitro cultured BCs. Moreover, BCs induced with RA and BMP4 could efficiently produce gonadal chimeric chick embryos. These results may greatly enhance the potential applications of BCs in biotechnology and basic research.

The current study examined the liver transcriptomic profiles of the Large White different in developmental periods. It was performed on pigs of two developmental stages: 70-day fetus (P70) and 70-day piglets (D70). The objective of the study was to identify genes associated with Large White liver lipid metabolism, growth and development. We sequenced eight sRNA libraries of liver samples from four Large White at P70 and D70 respectively. We totally obtained 19,202 genes. 4916 of them were found to be differentially expressed (DEGs) (p 0.05, fold change ≥ 1), of which 2502 were up-regulated and 2414 were down-regulated. GO enrichment and KEGG pathway analysis indicated that ACACA, ACADM, ACAA2 and HADH were simultaneously enriched in diverse pathways related to lipid metabolism, and so they were considered to be the promising candidate genes which could affect the porcine liver lipid metabolism. Notably, the gene insulin-like growth factor 1 (IGF1) which participated in somatotropic axis signaling was found to be up-regulated in D70 compared with P70. miRWalk and TargetScan softwares were used to screen the miRNAs which bound to the 3' untranslated region (3'UTR) of IGF1. After integration analysis with miRNAs sequencing data, miR-18b and miR-130b-3p were selected for further study. MiR-18b and miR-130b-3p were down-regulated in D70 compared with P70. Dual luciferase assays indicated that miR-18b and miR-130b-3p could obviously decrease (p 0.05) the fluorescence activity of the group transfected with the wild-type vector of IGF1 3'UTR, while the relative luciferase activity of the group transfected with the mutant vector of IGF1 3'UTR did not change significantly. Taken together, it indicated that miR-18b and miR-130b-3p could target IGF1 directly.

DDRGK domain-containing protein 1 (DDRGK1) is an important component of the newly discovered ufmylation system and its absence has been reported to induce extensive endoplasmic reticulum (ER) stress. Recently, emerging evidence indicates that the ufmylation system is correlated with autophagy, although the exact mechanism remains largely unknown. To explore the regulation mechanism of DDRGK1 on autophagy, in this study, we established an immortalized mouse embryonic fibroblast (MEF) cell lines harvested from the DDRGK1F/F:ROSA26-CreERT2 mice, in which DDRGK1 depletion can be induced by 4-hydroxytamoxifen (4-OHT) treatment. Here, we show that DDRGK1 deficiency in MEFs has a dual effect on autophagy, which leads to a significant accumulation of autophagosomes. On one hand, it promotes autophagy induction by impairing mTOR signaling; on the other hand, it blocks autophagy degradation by inhibiting autophagosome–lysosome fusion. This dual effect of DDRGK1 depletion on autophagy ultimately aggravates apoptosis in MEFs. Further studies reveal that DDRGK1 loss is correlated with suppressed lysosomal function, including impaired Cathepsin D (CTSD) expression, aberrant lysosomal pH, and v-ATPase accumulation, which might be a potential trigger for impairment in autophagy process. Hence, this study confirms a crucial role of DDRGK1 as an autophagy regulator by controlling lysosomal function. It may provide a theoretical basis for the treatment strategies of various physiological diseases caused by DDRGK1 deficiency.

Muscle fibers are closely related to human diseases and livestock meat quality. However, the genetics basis of microRNAs (miRNAs) in regulating muscle fibers is not completely understood. In this study, we constructed the whole genome-wide miRNA expression profiles of porcine fast-twitch muscle [biceps femoris (Bf)] and slow-twitch muscle [soleus (Sol)], and identified hundreds of miRNAs, including four skeletal muscle-highly expressed miRNAs, ssc-miR-378, ssc-let-7f, ssc-miR-26a, and ssc-miR-27b-3p. Moreover, we identified 63 differentially expressed (DE) miRNAs between biceps femoris vs. soleus, which are the key candidate miRNAs regulating the skeletal muscle fiber types. In addition, we found that the expression of DE ssc-miR-499-5p was significantly correlated to the expression of Myoglobin (r = 0.6872, P < 0.0001) and Myosin heavy chain 7 (MYH7; r = 0.5408, P = 0.0020), and pH45 min (r = 0.3806, P = 0.0380) and glucose content (r = -0.4382, P = 0.0154); while the expression of DE ssc-miR-499-3p was significantly correlated to the expression of Myoglobin (r = 0.5340, P = 0.0024) and pH45 min (r = 0.4857, P = 0.0065). Taken together, our data established a sound foundation for further studies on the regulatory mechanisms of miRNAs in skeletal muscle fiber conversion and meat quality traits in livestock, and could provide a genetic explanation of the role of miRNAs in human muscular diseases.

Emerging studies have indicated that long non-coding RNAs (lncRNAs) play important roles in skeletal muscle growth and development. Nevertheless, it remains challenging to understand the function and regulatory mechanisms of these lncRNAs in muscle biology and associated diseases. Here, we identify a novel lncRNA, Mir22hg, that is significantly upregulated during myoblast differentiation and is highly expressed in skeletal muscle. We validated that Mir22hg promotes myoblast differentiation in vitro. Mechanistically, Mir22hg gives rise to mature microRNA (miR)-22-3p, which inhibits its target gene, histone deacetylase 4 (HDAC4), thereby increasing the downstream myocyte enhancer factor 2C (MEF2C) and ultimately promoting myoblast differentiation. Furthermore, in vivo, we documented that Mir22hg knockdown delays repair and regeneration following skeletal muscle injury and further causes a significant decrease in weight following repair of an injured tibialis anterior muscle. Additionally, Mir22hg gives rise to miR-22-3p to restrict HDAC4 expression, thereby promoting the differentiation and regeneration of skeletal muscle. Given the conservation of Mir22hg between mice and humans, Mir22hg might constitute a promising new therapeutic target for skeletal muscle injury, skeletal muscle atrophy, as well as other skeletal muscle diseases., Graphical abstract, A novel lncRNA, Mir22hg, is highly expressed in skeletal muscle and could give rise to mature miR-22-3p to inhibit HDAC4 expression, thereby activating the downstream MEF2C pathway to promote skeletal muscle differentiation and regeneration.

A high level of reactive oxygen species (ROS) is widely considered one of the major causes of oocyte quality decline. Peroxynitrite is known as a powerful oxidant, which could induce multiple physical diseases. Recently, emerging pieces of evidences indicate that melatonin effectively promotes the development of oocytes, although the specific work mechanism remains to be further clarified. In this study, it was shown that peroxynitrite increased the level of ROS in porcine oocytes, which induced the apoptosis of oocytes, thereby leading to the obstruction of spindle assembly, depolymerization of actin, and decrease of polar body expulsion. These negative effects contributed to the failure of meiosis and ultimately blocked the maturation of porcine oocytes. As expected, it was found that melatonin effectively removed the accumulated ROS in oocytes, preventing oocytes from peroxynitrite-induced oocyte maturation failure, which might provide a novel approach to improve female livestock reproduction and cure female infertility in clinical practice.

Glycolytic potential (GP) calculated based on glucose, glycogen, glucose-6-phosphate, and lactate contents is a critical factor for multiple meat quality characteristics. However, the genetic basis of glycolytic metabolism is still unclear. In this study, we constructed six RNA-Seq libraries using longissimus dorsi (LD) muscles from pigs divergent for GP phenotypic values and generated the whole genome-wide gene expression profiles. Furthermore, we identified 25,880 known and 220 novel genes from these skeletal muscle libraries, and 222 differentially expressed genes (DEGs) between the higher and lower GP groups. Notably, we found that the Lactate dehydrogenase B (LDHB) and Fructose-2, 6-biphosphatase 3 (PFKFB3) expression levels were higher in the higher GP group than the lower GP group, and positively correlated with GP and lactic acid (LA), and reversely correlated with pH value at 45 min postmortem (pH45min). Besides, LDHB and PFKFB3 expression were positively correlated with drip loss measured at 48 h postmortem (DL48h) and drip loss measured at 24 h postmortem (DL24h). Collectively, we identified a serial of DEGs as the potential key candidate genes affecting GP and found that LDHB and PFKFB3 are closely related to GP and GP-related traits. Our results lay a solid basis for in-depth studies of the regulatory mechanisms on GP and GP-related traits in pigs.

Simple Summary Myostatin (MSTN) is a transcriptional growth factor that inhibits the development and growth of skeletal muscle. The MSTN-deficient animals display an increase in skeletal muscle mass known as double-muscling. Therefore, MSTN becomes an important target for improving lean meat production in livestock husbandry. There are many local pig breeds in China, but because of the slow growth, poor feed conversion, and low lean meat percentage and other unsatisfactory qualities, pure local breeds are rarely used on commercial farms. The objective of this study is to evaluate the effects of MSTN single allele mutation on carcass composition in Meishan crossbred pigs and demonstrate a way to increase lean meat yield while maintaining prolificacy and good meat quality of local pig crossbreeds. This has significant implications for the widespread use and conservation of local pig breeds in China. Abstract The Meishan pig is a traditional Chinese native breed, known for its excellent reproduction performance that is widely used in commercial pig production through two-way or three-way crossbreeding systems. However, the lean meat yield of Meishan crossbred pigs is still very low and cannot meet the market demand. To evaluate the lean meat yield of Meishan crossbred pigs, six wild-type Meishan sows were artificially inseminated by using the MSTN+/− Duroc boar semen in this experiment. Some reproductive performance-related traits of Meishan sows were recorded to ensure that semen from MSTN knockout Duroc boar did not affect offspring production, including total births, live births, sex, and litter weight. In total, 73 piglets were obtained and 63 were alive. Male to female ratio was close to 1: 1. because of factors such as disease, only 43 pigs were utilized, including 28 MSTN mutant pigs (MSTN+/−) and 15 MSTN homozygous pigs (MSTN+/+). We compared the growth performance and carcass performance of these full or half-sib populations and found that there were no differences between MSTN+/− and MSTN+/+ genotypes for live animal measures including average daily gain (ADG), body dimensions, or ultrasonic measurement of fat thickness when pigs were harvested after 120 days of feeding. Conversely, the MSTN+/− pigs had higher dressing percentage and lean meat percentage, lower level of carcass fat, larger longissimus muscle area, less percentage of skin and skeleton, thinner average backfat thickness, and lower intramuscular fat (IMF) content than MSTN+/+ pigs. In conclusion, the production of MSTN+/− mutant progeny from Meishan females resulted in improved carcass composition, providing a feasible solution to improve the lean meat yield of Chinese local fat-type pig breeds.

The intronic microRNA, miR-125b, plays a vital role in promyelocytic and hematopoietic stem cells, and in the development and apoptosis of cancer cells. In this study, we showed that miR-125b regulates granulosa cell (GC) apoptosis in the yak ovary. Bioinformatic analyses and luciferase reporter assays demonstrated that bone morphogenetic protein receptor type 1B (BMPR1B) is an miR-125b target. miR-125b overexpression induced apoptosis in yak GC, and affected the mRNA and protein expression of BMPR1B and the ratio of Bcl2/Bax. Silencing of miR-125b decreased the rate of yak GC apoptosis and increased the ratio of Bcl2/Bax. In addition, the effects of an miR-125b inhibitor were overturned by cotransfection with siRNA-BMPR1B2 (siRNA-299) in yak GC. Together, these results demonstrated that miR-125b regulates GC apoptosis in the yak ovary by targeting BMPR1B.

The different skeletal muscle fiber types exhibit distinctively different physiological and metabolic properties, and have been linked to both human metabolic diseases and meat quality traits in livestock. Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression, but regulatory mechanisms of skeletal muscle fibers involved in circRNAs remain poorly understood. Here, we constructed circRNA expression profiles of three fast-twitch biceps femoris (Bf) and three slow-twitch soleus (Sol) muscles in pigs using RNA-seq and identified 16,342 distinct circRNA candidates. Notably, 242 differentially expressed (DE) circRNAs between Bf and Sol muscles were identified, including 105 upregulated and 137 downregulated circRNAs, and are thus potential candidates for the regulation of skeletal muscle fiber conversion. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of host genes of DE circRNAs revealed that host genes were mainly involved in skeletal muscle fiber-related GO terms (e.g., muscle contraction, contractile fiber part, and Z disk) and skeletal muscle fiber-related signaling pathways (e.g., AMPK and cGMP-PKG). We also constructed co-expression networks of DE circRNA-miRNA-mRNA using previously acquired high-throughput sequencing mRNA and miRNA data, from which 112 circRNA-miRNA and 95 miRNA-mRNA interactions were identified. Multiple circRNAs essentially serve as a sponge for miR-499-5p, which is preferentially expressed in slow-twitch muscle and reduces the severity of Duchenne muscular dystrophy (DMD). Taken together, a series of novel candidate circRNAs involved in the growth and development of porcine skeletal muscle was identified. Furthermore, they provide a comprehensive circRNA resource for further in-depth research on the regulatory mechanisms of circRNA in the formation of skeletal muscle fiber, and may provide insights into human skeletal muscle diseases.

Small molecules discovered during the recent years can be used to regulate the growth of embryonic stem cells (ES cells). Chicken blastodermal cells (cBCs) play an important role in both basic and transgenic researches as an important ES cell. However, the regulatory mechanism of small molecules involved in the self-renewal and pluripotency of cBCs remains unknown. This study revealed that the small molecule, SC1, can maintain cBCs in an undifferentiated, pluripotent state in serum- and feeder-free E8 media without leukaemia inhibitory factor. Furthermore, SC1 inhibits downregulation of pluripotency-related genes caused by retinoic acid and promotes the proliferation of cBCs. Furthermore, the results of this study indicated that SC1 functions by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation, thus promoting the expression of pluripotency-related genes and maintaining the pluripotency of cBCs. The results also demonstrated that SC1 sustains the self-renewal capacity and pluripotency of cBCs cells by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation. This kind of regulatory mechanism might be conserved in avian ES cells. Other molecules, similar to SC1, might provide insights into the molecular mechanisms that control the fate of stem cells and ultimately help in-vivo stem cell biology and therapy.

Meiosis is essential for gametogenesis and exhibits sex-specific property during embryonic development. Retinoic acid (RA) signalling initiates germ cell meiosis by activating Stra8 (stimulated by RA gene 8). Although additional factors are involved in regulating the meiotic initiation of germ cells, their regulatory mechanisms are unclear. In this study, we found that Polycomb repressive complex 1 (PRC1) is largely expressed in chicken ovarian germ and somatic cells during early stages of meiosis. We demonstrated that PRC1 regulates Stra8, pluripotent factors and paracrine factors (Notch ligands) leading to a synergistic effect on the suppression of germ cell meiotic initiation. Finally, we observed that repression of PRC1 resulted in precocious meiotic initiation and apoptosis of ovarian cells in vivo. These results aid in understanding the regulation of meiotic initiation in germ cells by PRC1 and provide evidence to support the hypothesis that regulation of meiotic initiation is conserved in higher vertebrates.

Simple Summary The improvement of porcine meat quality is one of the most challenging tasks in pig breeding. The identification and utilization of major genes and variations affecting meat quality traits has become a research hotspot in molecular breeding of pigs. In this study, we analyzed the characteristics of porcine Prospero-related homeobox 1 (Prox1) gene to lay a solid foundation for further functional study. The expression pattern of Prox1, as well as the correlation and association analysis of Prox1 with meat quality traits, indicates that Prox1 can be targeted to improve porcine meat quality traits. Abstract Prox1 is involved in muscle fiber conversion, adult-onset obesity, and type 2 diabetes. However, information regarding porcine Prox1 and its relationship with meat quality traits is still unknown. In this study, we characterized the full-length cDNA and proximal promoter of two transcript variants of porcine Prox1. Moreover, Prox1 was expressed abundantly in the skeletal muscle and its expression was higher in the soleus muscle than that in the biceps femoris muscle. Its expression pattern in the high and low meat color (redness) value a* groups was similar to that of myoglobin and MyHC I, but opposed to that of MyHC IIB. Importantly, there was a significant positive correlation between Prox1 expression and meat color (redness) value a* (r = 0.3845, p = 0.0394), and a significant negative correlation between Prox1 expression and drip loss (r = −0.4204, p = 0.0232), as well as the ratio of MyHC IIB to MyHC I expression (r = −0.3871, p = 0.0380). In addition, we found that the polymorphisms of three closely linked SNPs in Prox1 promoter 1 were significantly associated with pH24h in a pig population. Taken together, our data provide valuable insights into the characteristics of porcine Prox1 and indicate that Prox1 is a promising candidate gene affecting meat quality traits.

The rapid development of the Internet of things (IoT) promotes the close combination of cyberspace and physical space, thus humans can dynamically manage their own life in social space to achieve a smart life. However, as more and more physical objects (eg, people, devices) accessing to the IoT, a lot of sensitive information related to our privacy integrates with the IoT. Therefore, the security and privacy have become a key issue for the IoT. In order to avoid the data leakage and illegal access in the IoT, people have proposed the access control scheme for physical objects. The secure access control of physical objects in the IoT is the cornerstone of IoT security. This paper mainly analyzed the requirements of access control for physical objects in the IoT. For different needs, we further summarized the corresponding schemes of access control, then we discussed the challenges and future development of physical objects in the IoT.

As the follicle develops, the thickening of the granulosa compartment leads to progressively deficient supply of oxygen in granulosa cells (GCs) due to the growing distances from the follicular vessels. These conditions are believed to cause hypoxia in GCs during folliculogenesis. Upon hypoxic conditions, several types of mammalian cells have been reported to undergo cell cycle arrest. However, it remains unclear whether hypoxia exerts any impact on cell cycle progression of GCs. On the other hand, although the GCs may live in a hypoxic environment, their mitotic capability appears to be unaffected in growing follicles. It thus raises the question whether there are certain intraovarian factors that might overcome the inhibitory effects of hypoxia. The present study provides the first evidence suggesting that cobalt chloride (CoCl2)-mimicked hypoxia prevented G1-to-S cell cycle progression in porcine GCs. In addition, we demonstrated that the inhibitory effects of CoCl2 on GCs cell cycle are mediated through hypoxia-inducible factor-1 alpha/FOXO1/Cdkn1b pathway. Moreover, we identified insulin-like growth factor-I (IGF-I) as an intrafollicular factor required for cell cycle recovery by binding to IGF-I receptor in GCs suffering CoCl2 stimulation. Further investigations confirmed a role of IGF-I in preserving G1/S progression of CoCl2-treated GCs via activating the cyclin E/cyclin-dependent kinase2 complex through the phoshatidylinositol-3 kinase/protein kinase B (AKT)/FOXO1/Cdkn1b axis. Although the present findings were based on a hypoxia mimicking model by using CoCl2, our study might shed new light on the regulatory mechanism of GCs cell cycle upon hypoxic stimulation.

The Meishan pig is a traditional Chinese native breed, known for its excellent reproduction performance that is widely used in commercial pig production through two-way or three-way crossbreeding systems. However, the lean meat yield of Meishan crossbred pigs is still very low and cannot meet the market demand. To evaluate the lean meat yield of Meishan crossbred pigs, six wild-type Meishan sows were artificially inseminated by using the MSTN+/&minus, Duroc boar semen in this experiment. Some reproductive performance-related traits of Meishan sows were recorded to ensure that semen from MSTN knockout Duroc boar did not affect offspring production, including total births, live births, sex, and litter weight. In total, 73 piglets were obtained and 63 were alive. Male to female ratio was close to 1: 1. because of factors such as disease, only 43 pigs were utilized, including 28 MSTN mutant pigs (MSTN+/&minus, ) and 15 MSTN homozygous pigs (MSTN+/+). We compared the growth performance and carcass performance of these full or half-sib populations and found that there were no differences between MSTN+/&minus, and MSTN+/+ genotypes for live animal measures including average daily gain (ADG), body dimensions, or ultrasonic measurement of fat thickness when pigs were harvested after 120 days of feeding. Conversely, the MSTN+/&minus, pigs had higher dressing percentage and lean meat percentage, lower level of carcass fat, larger longissimus muscle area, less percentage of skin and skeleton, thinner average backfat thickness, and lower intramuscular fat (IMF) content than MSTN+/+ pigs. In conclusion, the production of MSTN+/&minus, mutant progeny from Meishan females resulted in improved carcass composition, providing a feasible solution to improve the lean meat yield of Chinese local fat-type pig breeds.