Service opening and wages of manufacturing firms: Evidence from China.

Based on the 'Catalogue for the Guidance of Foreign Investment' and the input-output table issued by the National Bureau of Statistics, this paper constructs the service opening index from 1998 to 2013. With this indicator, we empirically study the impact of the service industry opening-up on firm wage. Our research yields a few findings. First, the service industry opening-up can significantly improve the level of firm wage. This result is still significantly valid after various robustness test and endogenous treatment. Moreover, after segmenting upstream service sources into details, the opening-up of the finance, telecommunication, and sales service sectors can promote the growth of firm wage. Second, the heterogeneity analysis shows that the service industry opening-up exerts a greater impact on firms' wage for firms in the central and western regions rather than eastern region, and for firms in the "post rich" regions rather than "pre-rich" regions, as well as firms in more severe market segmentation rather than regions with less market segmentation. Finally, according to the analysis of the impact mechanism, the opening-up of the service industry mainly promote firm wage through three channels: improving labor productivity, operating income, and human capital. Furthermore, the analysis of technical differences in service input displays that the service industry opening-up exerts a greater impact on firms' wage for firms in high-tech service industry. The analysis of labor income distribution shows that the opening-up of the service industry can also significantly increase the share of labor income of firm, especially in the opening-up of finance, telecommunication, and sales service industry.

IFI16 promotes the progression of clear cell renal cell carcinoma through the IL6/PI3K/AKT axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. METHODS: We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. RESULTS: IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). CONCLUSION: IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.

Clinical risk prediction model and external validation of positive surgical margin in laparoscopic radical prostatectomy based on MRI lesion location.

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.

Neural Stem Cells Transplanted into Rhesus Monkey Cortical Traumatic Brain Injury Can Survive and Differentiate into Neurons.

Cortical traumatic brain injury (TBI) is a major cause of cognitive impairment accompanied by motor and behavioral deficits, and there is no effective treatment strategy in the clinic. Cell transplantation is a promising therapeutic strategy, and it is necessary to verify the survival and differentiation of cells after transplantation in large animal models like rhesus monkeys. In this study, we transplanted neural stem cells (NSCs) and simultaneously injected basic fibroblast growth factor/epidermal growth factor (bFGF/EGF) into the cortex (visual and sensory cortices) of rhesus monkeys with superficial TBI. The results showed that the transplanted NSCs did not enter the cerebrospinal fluid (CSF) and were confined to the transplantation site for at least one year. The transplanted NSCs differentiated into mature neurons that formed synaptic connections with host neurons, but glial scar formation between the graft and the host tissue did not occur. This study is the first to explore the repairing effect of transplanting NSCs into the superficial cerebral cortex of rhesus monkeys after TBI, and the results show the ability of NSCs to survive long-term and differentiate into neurons, demonstrating the potential of NSC transplantation for cortical TBI.

Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids.

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

Analysis of the Risk Factors for Massive Hemorrhage after PCNL in the Oblique Supine Position.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is a proven and efficient treatment method; Nevertheless, it is essential to note that there is still a risk of significant bleeding. The purpose of this paper is to explore the risk factors for massive hemorrhage after PCNL in the oblique supine position and provide a basis for the development of measures to prevent massive hemorrhage. METHODS: The clinical data of 97 patients who underwent PCNL in the oblique supine position at Changshu No. 2 People's Hospital from January 2019 to December 2020 were retrospectively analyzed. Patients were placed in the massive hemorrhage group if their hemoglobin levels decreased by ≥20 g/L 24 h after the operation, and the other patients were placed in the nonmassive hemorrhage group. Differences in sex, age, body mass index (BMI), hypertension, diabetes, surgical side, perirenal fat stranding (PFS), calculus long diameter, surgical access, and operation time were compared between the two groups to determine the risk factors for massive bleeding. Multivariable logistic regression analysis was used to determine the risk factors for massive hemorrhage after PCNL. RESULTS: There were no significant differences in sex, BMI, hypertension, diabetes, surgical side, or calculus long diameter between the two groups (p > 0.05), and there were statistically significant differences in age, PFS, surgical access, and operation time (p < 0.05). Multivariate logistic regression analysis indicated that PFS and extensive surgical access were independent risk factors (p < 0.05). CONCLUSIONS: PFS and extensive surgical access were independent risk factors. Carefully reading computed tomography (CT) films before surgery and reducing the size of the surgical access area are important measures for reducing the risk of massive hemorrhages.

Analysis of the Risk Factors for Massive Hemorrhage after PCNL in the Oblique Supine Position

Background: Percutaneous nephrolithotomy (PCNL) is a proven and efficient treatment method; Nevertheless, it is essential to note that there is still a risk of significant bleeding. The purpose of this paper is to explore the risk factors for massive hemorrhage after PCNL in the oblique supine position and provide a basis for the development of measures to prevent massive hemorrhage. Methods: The clinical data of 97 patients who underwent PCNL in the oblique supine position at Changshu No. 2 People’s Hospital from January 2019 to December 2020 were retrospectively analyzed. Patients were placed in the massive hemorrhage group if their hemoglobin levels decreased by ≥20 g/L 24 h after the operation, and the other patients were placed in the nonmassive hemorrhage group. Differences in sex, age, body mass index (BMI), hypertension, diabetes, surgical side, perirenal fat stranding (PFS), calculus long diameter, surgical access, and operation time were compared between the two groups to determine the risk factors for massive bleeding. Multivariable logistic regression analysis was used to determine the risk factors for massive hemorrhage after PCNL. Results: There were no significant differences in sex, BMI, hypertension, diabetes, surgical side, or calculus long diameter between the two groups (p > 0.05), and there were statistically significant differences in age, PFS, surgical access, and operation time (p < 0.05). Multivariate logistic regression analysis indicated that PFS and extensive surgical access were independent risk factors (p < 0.05). Conclusions: PFS and extensive surgical access were independent risk factors. Carefully reading computed tomography (CT) films before surgery and reducing the size of the surgical access area are important measures for reducing the risk of massive hemorrhages (AU)

Deep learning-based activity recognition and fine motor identification using 2D skeletons of cynomolgus monkeys.

Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction. However, action recognition currently used in non-human primate (NHP) research relies heavily on intense manual labor and lacks standardized assessment. In this work, we established two standard benchmark datasets of NHPs in the laboratory: MonkeyinLab (MiL), which includes 13 categories of actions and postures, and MiL2D, which includes sequences of two-dimensional (2D) skeleton features. Furthermore, based on recent methodological advances in deep learning and skeleton visualization, we introduced the MonkeyMonitorKit (MonKit) toolbox for automatic action recognition, posture estimation, and identification of fine motor activity in monkeys. Using the datasets and MonKit, we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome (RTT). MonKit was used to assess motor function, stereotyped behaviors, and depressive phenotypes, with the outcomes compared with human manual detection. MonKit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency, thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.

Analysis of the efficacy of a single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy.

BACKGROUND: Radical cystectomy and urinary diversion are the standard surgical treatments for patients with muscle-invasive or high-risk, or recurrent non-muscle-invasive bladder cancer. Although this approach significantly prolongs patient survival, it can lead to postoperative complications. This study aims to compare the efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma to those of cutaneous ureterostomy with two stomas and an ileal conduit as a means of urinary diversion after radical cystectomy. The findings of this study will provide valuable information for healthcare providers in selecting the appropriate urinary diversion method for their patients. METHODS: The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomy were retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs,and postoperative quality of life were compared between the three groups of patients. RESULTS: A significant difference in the operative time was found between the three groups (P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or bladder cancer index (BCI) score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant (P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients (P = 0.006). CONCLUSION: A single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy may result in shorter surgery time, increased success rates for initial catheter removal, and lower medical expenses. However, to confirm these findings, further prospective randomized clinical trials are necessary.

Ex utero monkey embryogenesis from blastocyst to early organogenesis.

The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.

Efficient Modulation of Exon Skipping via Antisense Circular RNAs.

Splice-switching antisense oligonucleotides (ASOs) and engineered U7 small nuclear ribonucleoprotein (U7 Sm OPT) are the most commonly used methods for exon skipping. However, challenges remain, such as limited organ delivery and repeated dosing for ASOs and unknown risks of by-products produced by U7 Sm OPT. Here, we showed that antisense circular RNAs (AS-circRNAs) can effectively mediate exon skipping in both minigene and endogenous transcripts. We also showed a relatively higher exon skipping efficiency at the tested Dmd minigene than U7 Sm OPT. AS-circRNA specifically targets the precursor mRNA splicing without off-target effects. Moreover, AS-circRNAs with adeno-associated virus (AAV) delivery corrected the open reading frame and restored the dystrophin expression in a mouse model of Duchenne muscular dystrophy. In conclusion, we develop an alternative method for regulating RNA splicing, which might be served as a novel tool for genetic disease treatment.

Molecular and cellular mechanisms of the first social relationship: A conserved role of 5-HT from mice to monkeys, upstream of oxytocin.

Maternal affiliation by infants is the first social behavior of mammalian animals. We report here that elimination of the Tph2 gene essential for serotonin synthesis in the brain reduced affiliation in mice, rats, and monkeys. Calcium imaging and c-fos immunostaining showed maternal odors activation of serotonergic neurons in the raphe nuclei (RNs) and oxytocinergic neurons in the paraventricular nucleus (PVN). Genetic elimination of oxytocin (OXT) or its receptor reduced maternal preference. OXT rescued maternal preference in mouse and monkey infants lacking serotonin. Tph2 elimination from RN serotonergic neurons innervating PVN reduced maternal preference. Reduced maternal preference after inhibiting serotonergic neurons was rescued by oxytocinergic neuronal activation. Our genetic studies reveal a role for serotonin in affiliation conserved from mice and rats to monkeys, while electrophysiological, pharmacological, chemogenetic, and optogenetic studies uncover OXT downstream of serotonin. We suggest serotonin as the master regulator upstream of neuropeptides in mammalian social behaviors.

Phenotypes and genetic etiology of spontaneous polycystic kidney and liver disease in cynomolgus monkey.

Introduction: Polycystic kidney disease (PKD) is a common autosomal dominant or recessive genetic disease, often accompanied by polycystic liver disease (PLD). Many cases of PKD in animals have been reported. However, little is known about the genes that cause PKD in animals. Methods: In this study, we evaluated the clinical phenotypes of PKD in two spontaneously aged cynomolgus monkeys and explored the genetic etiology using whole-genome sequencing (WGS). Ultrasonic and histological consequences were further investigated in PKD- and PLD-affected monkeys. Results: The results indicated that the kidneys of the two monkeys had varying degrees of cystic changes, and the renal cortex was thinned and accompanied by fluid accumulation. As for hepatopathy, inflammatory cell infiltration, cystic effusion, steatosis of hepatocytes, and pseudo-lobular were found. Based on WGS results, the variants of PKD1:(XM_015442355: c.1144G>C p. E382Q) and GANAB: (NM_001285075.1: c.2708T>C/p. V903A) are predicted to be likely pathogenic heterozygous mutations in PKD- and PLD-affected monkeys. Discussion: Our study suggests that the cynomolgus monkey PKD and PLD phenotypes are very similar to those in humans, and are probably caused by pathogenic genes homologous to humans. The results indicate that cynomolgus monkeys can be used as the most appropriate animal model for human PKD pathogenesis research and therapeutic drug screening.

Extracapsular extension of transitional zone prostate cancer miss-detected by multiparametric magnetic resonance imaging.

OBJECTIVES: To demonstrate the importance of extracapsular extension (ECE) of transitional zone (TZ) prostate cancer (PCa), examine the causes of its missed detection by Mp-MRI, and develop a new predictive model by integrating multi-level clinical variables. MATERIALS AND METHODS: This retrospective study included 304 patients who underwent laparoscopic radical prostatectomy after 12 + X needle transperineal transrectal ultrasound (TRUS)-MRI-guided targeted prostate biopsy from 2018 to 2021 in our center was performed. RESULTS: In this study, the incidence rates of ECE were similar in patients with MRI lesions in the peripheral zone (PZ) and TZ (P = 0.66). However, the missed detection rate was higher in patients with TZ lesions than in those with PZ lesions (P < 0.05). These missed detections result in a higher positive surgical margin rate (P < 0.05). In patients with TZ lesions, detected MP-MRI ECE may have grey areas: the longest diameters of the MRI lesions were 16.5-23.5 mm; MRI lesion volumes were 0.63-2.51 ml; MRI lesion volume ratios were 2.75-8.86%; PSA were 13.85-23.05 ng/ml. LASSO regression was used to construct a clinical prediction model for predicting the risk of ECE in TZ lesions from the perspective of MRI and clinical features, including four variables: the longest diameter of MRI lesions, TZ pseudocapsule invasion, ISUP grading of biopsy pathology, and number of positive biopsy needles. CONCLUSIONS: Patients with MRI lesions in the TZ have the same incidence of ECE as those with lesions in the PZ, but a higher missed detection rate.

Identification and validation of an immune-related lncRNAs signature to predict the overall survival of ovarian cancer.

Ovarian cancer (OC) is the most lethal gynecological cancer in women. Studies had reported that immune-related lncRNAs signatures were valuable in predicting the survival and prognosis of patients with various cancers. In our study, the prognostic value of immune-related lncRNAs was investigated in OC patients from TCGA-RNA-seq cohort (n=378) and HG-U133_Plus_2 cohort (n=590), respectively. Pearson correlation analysis was implemented to screen the immune-related lncRNA and then univariate Cox regression analysis was performed to explore their prognostic value in OC patients. Five prognostic immune-related lncRNAs were identified as prognostic lncRNAs. Besides, they were inputted into a LASSO Cox regression to establish and validate an immune-related lncRNA prognostic signature in TCGA-RNA-Seq cohort and HG-U133_Plus_2 cohort, respectively. Based on the best cut-off value of risk score, patients were divided into high- and low-risk groups. Survival analysis suggested that patients in the high-risk group had a worse overall survival (OS) than those in the low-risk group in both cohorts. The association between clinicopathological feathers and risk score was then evaluated by using stratification analysis. Moreover, we constructed a nomogram based on risk score, age and stage, which had a strong ability to forecast the OS of the OC patients. The influence of risk score on immune infiltration and immunotherapy response were assessed and the results suggested that patients with high-risk score might recruit multiple immune cells and stromal cells, leading to facilitating immune surveillance evasive. Ultimately, we demonstrated that the risk model was associated with chemotherapy response of multiple antitumor drugs, especially for paclitaxel, metformin and veliparib, which are commonly used in treating OC patients. In conclusion, we constructed a novel immune-related lncRNA signature, which had a potential prognostic value for OC patients and might facilitate personalized counselling for immunotherapy and chemotherapy.

General synthesis strategy of ZrO2 nanofilms with few-atom layered thickness for boosting triethylamine detection.

ZrO2, a traditional inert transition metal oxide (TMO), can be prepared into ZrO2 nanofilms (NFs) with a single-layer thickness of only 2.5 nm through the generally applicable two-dimensional TMO synthesis strategy reported by us, and has displayed remarkable sensitivity and selectivity properties for triethylamine gas detection.

Advances in the pathogenesis of Rett syndrome using cell models.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders. MeCP2 protein loss-of-function in neural lineage cells is the main cause of RTT pathogenicity. As it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models, cell models cultured in vitro play indispensable roles. Here we reviewed the research progress in the pathogenesis of RTT at the cellular level, summarized the preclinical-research-related applications, and prospected potential future development.