The Protective Role of Vitamin E against Oxidative Stress and Immunosuppression Induced by Non-Esterified Fatty Acids in Bovine Peripheral Blood Leukocytes.

High levels of non-esterified fatty acids (NEFAs) during the transition period lead to increased oxidative stress and immunosuppression in cows. Feeding them a vitamin-E-supplemented diet reduces reactive oxygen species (ROS) levels in the blood and diminishes immunosuppression in the transition period. However, whether the restoration of immune cell function occurs through the direct action of vitamin E in cells is still a topic that requires further discussion. Therefore, in this experiment, we aimed to investigate the effect of NEFAs on peripheral blood leukocytes (PBLs) and whether vitamin E mitigates the impact of NEFAs. We employed three groups: (1) blank, (2) NEFA only, and (3) pre-culturing with vitamin E before NEFA treatment (VENEFA). In peripheral blood mononuclear cells (PBMCs), there were no differences in vitamin E content among the three groups. However, in the vitamin E pre-treatment group, the vitamin E levels of polymorphonuclear neutrophils (PMNs) were significantly higher than those in the other two groups. NEFA levels increased malondialdehyde (MDA) levels in PBMCs, but pre-treatment with vitamin E reduced accumulation of MDA levels. Regarding the expression of proinflammatory genes, NEFAs increased the expression of interleukin-1ß in PBMCs and colony-stimulating factor 2 in PMNs. Vitamin E pre-treatment restored the increase in interleukin-1ß levels caused by NEFAs in PBMCs. None of the groups affected the phagocytosis of PMNs. Few studies have confirmed that NEFAs cause oxidative stress in bovine PBLs. In summary, this study found that NEFAs induce oxidative stress in PBLs and alter the expression of inflammation-related genes; meanwhile, vitamin E can reduce some of the effects caused by NEFAs. This result may suggest that vitamin E can assist bovine PBLs in resisting the immune suppression caused by an NEB during the transition period.

[Clinical and genetic characteristics of a child with Developmental and epileptic encephalopathy 104 due to variant of ATP6V0A1 gene].

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104). METHODS: A child who had presented at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl's ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c.2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+PM2_Supporting+PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. CONCLUSION: The c.2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

Evaluation indices of the temperature difference of subgrade and the optimization of mitigation measures in cold regions.

With the construction and operation of railways in cold regions, the asymmetric deformation of subgrades due to the difference in the transverse ground temperature has become a prominent issue. A comprehensive evaluation of the transverse ground temperature difference and investigation of the corresponding mitigation measures should be conducted to avoid or minimize the damage resulting from this difference, thereby improving subgrade stability and reducing deformation. In this study, the time history variations in the homogeneity and symmetry indices of the ground temperature at typical instances that reflect the spatial and temporal changes in the temperature difference of the subgrade were proposed as evaluation indices. The feasibility of these evaluation indices was verified through numerical models with different types of anti-frost berms. Subsequently, the numerical models were used to analyze the ground temperature evaluation indices of a subgrade with expanded polystyrene (EPS) insulation board and polyurethane (PU) insulation board at different locations. Additionally, the performances of each mitigation measure in eliminating or reducing the ground temperature difference were assessed and compared. The results show that all the mitigation measures could improve the homogeneity and symmetry of the ground temperature distribution. The maximum mitigation rates for the homogeneity and symmetry are 97.87% and 45.90%, respectively. This study provides a comprehensive evaluation method for the temperature difference of subgrades constructed in cold regions and a theoretical reference for the selection of anti-frost measures in the design, operation, and maintenance of subgrades in cold regions.

Silencing LCN2 enhances RSL3-induced ferroptosis in T cell acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a life-threatening malignancy and therapeutic toxicity remains a huge challenge for survival rates. A novel iron-dependent form of cell death, ferroptosis, shows potentials in cancer therapy. This study aimed to identify ferroptosis-associated hub genes within a proteinprotein interaction (PPI) network. METHODS: We screened differential expressed genes (DEGs) in GSE46170 dataset and obtained ferroptosis-related genes from FerrDb database. Through overlapping between DEGs and ferroptosis-related genes, ferroptosis-associated DEGs were identified for further PPI network construction. Molecular complex detection (MCODE) algorithm in Cytoscape was employed to determine tightly connected protein clusters. Chord diagram of Gene Ontology (GO) was generated to reveal the potential biological process of hub genes. Through transfection with siRNA of lipocalin 2 (LCN2) into TALL cells, the regulatory role of LCN2 in ferroptosis was investigated. RESULTS: Venn diagram identified a total of 37 ferroptosis-associated DEGs between GSE46170 and ferroptosis-associated genes, which were mainly enriched in ferroptosis and necroptosis. Based on PPI network analysis, 5 hub genes (LCN2, LTF, HP, SLC40A1 and TFRC) were found. These hub genes were involved in iron ion transport and could distinguish T-ALL from normal individuals. Further experimental studies demonstrated that LCN2 was highly expressed in T-ALL, while silencing LCN2 promoted RSL3-induced ferroptotic cell death in T-ALL cells. CONCLUSION: This study identified novel ferroptosis-associated hub genes, which shed new insights into the underlying mechanism of ferroptosis in T-ALL and also provide promising therapeutic targets for T-ALL.

Improved 2†µm broadband luminescence in Tm3+/Ho3+ doping tellurite glass.

Tm3+/Ho3+ doping tellurite glasses (TeO2-ZnO-La2O3) were prepared by applying melt-quenching technique, and the ∼2.0 µm band luminescence characteristics were examined. A broadband and relatively flat luminescence at 1600 to 2200 nm was observed in the tellurite glass co-doped by 1.0 mol% Tm2O3 and 0.085 mol% Ho2O3 under the excitation of 808 nm laser diode (LD), which is the result of spectral overlapping of 1.83 µm band of Tm3+ ions and 2.0 µm band of Ho3+ ions. Further, about 103% enhancement was acquired after the introduction of 0.1 mol% CeO2 and 7.5 mol% WO3 at the same time, which is primarily caused by the cross-relaxation between Tm3+ and Ce3+ ions together with the enhanced energy transfer from the Tm3+:3F4 level to Ho3+:5I7 level due to the increase in phonon energy. Spectral characteristics associated with the radiative transition of Ho3+ and Tm3+ ions on the basis of Judd-Ofelt theory, and the fluorescence decay behaviors after the addition of Ce3+ ions and WO3 component were analyzed to understand the broadband and luminescence enhancement. The findings in this work indicate that tellurite glass with optimal Tm3+-Ho3+-Ce3+ tri-doping combination and appropriate amount of WO3 is a prospective candidate for broadband optoelectronic devices operated in the infrared bands.

[Clinical and genetic analysis of three children with Menkes disease due to variants of ATP7A gene].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of three children with Menkes disease. METHODS: Three children who had presented at the Children's Medical Center, the Affiliated Hospital of Guangdong Medical University from January 2020 to July 2022 were selected as the study subjects. Clinical data of the children were reviewed. Genomic DNA was extracted from peripheral blood samples of the children, their parents and sister of child 1. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq), and bioinformatic analysis. RESULTS: Child 1 was a 1-year-and-4-month male, and children 2 and 3 were monozygotic twin males aged 1-year-and-10-month. The clinical manifestations of the three children have included developmental delay and seizures. WES showed that child 1 has harbored a c.3294+1G>A variant of the ATP7A gene. Sanger sequencing confirmed that his parents and sister did not carry the same variant, suggesting that it was de novo. Children 2 and 3 had carried a c.77266650_77267178del copy number variation. CNV-seq results showed that their mother has carried the same variant. By searching the HGMD, OMIM and ClinVar databases, the c.3294+1G>A was known to be pathogenic. No carrier frequency has been recorded in the 1000 Genomes, ESP, ExAC and gnomAD databases. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the ATP7A gene c.3294+1G>A variant was predicted to be pathogenic. The c.77266650_77267178del variant has involved exons 8 to 9 of the ATP7A gene. ClinGen online system score for it was 1.8, which was also considered to be pathogenic. CONCLUSION: The c.3294+1G>A and c.77266650_ 77267178del variants of the ATP7A gene probably underlay the Menkes disease in the three children. Above finding has enriched the mutational spectrum of Menkes disease and provided a basis for clinical diagnosis and genetic counseling.

Ketogenic Diet Attenuates Refractory Epilepsy of Harel-Yoon Syndrome With ATAD3A Variants: A Case Report and Review of Literature.

BACKGROUND: Harel-Yoon syndrome is a disease caused by variants in the ATAD3A gene, which manifest as global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. The aim of this study is to summarize the clinical and gene mutation characteristics of a child with refractory epilepsy caused by ATAD3A gene mutation. METHODS: The whole-exome sequencing combined with copy number variation analysis could help to understand the genetic diversity and underlying disease mechanisms in ATAD3A gene mutation. RESULTS: We report a Chinese boy with Harel-Yoon syndrome presenting with refractory epilepsy, hypotonia, global developmental delay, and congenital cataract through whole-exome sequencing. Genetic analysis showed a missense mutation, c.251T>C(p.Thr84Met) in the ATAD3A gene (NM_001170535.1). Further copy number variation analysis identified a novel heterozygous deletion on chromosome1p36.33, which spans ATAD3A exon 1 and 2 regions. Multiple antiepileptic drugs failed to control his seizures. Eventually, seizure was controlled through ketogenic diet (KD). CONCLUSION: Our case shows the potential diagnostic role of whole-exome sequencing in Harel-Yoon syndrome and expands the ATAD3A gene mutation spectrum. Multiple antiepileptic drugs failed to control refractory epilepsy in Harel-Yoon syndrome. The KD therapy may be effective for patients with refractory epilepsy who carry the ATAD3A variants.

Family and Relationship Quality among Young Adults with Different Sexual Orientations in Urban China: The Mediating Effects of Life Satisfaction and Self-Esteem.

This study explored the ambivalent effects of family on the close relationship quality of Chinese young adults. From a national estimate of the urban population across mainland China, 5,089 participants aged 20-39 were recruited for this study. A three-dimensional conceptualization was applied to identify three groups with different sexual orientations in this study. Group A comprised participants who identified as sexual minority people; Group B comprised participants who identified as heterosexuals but were not exclusively attracted to one sex and/or individuals who had had same-sex sexual experiences; Group C comprised participants who identified as heterosexuals. Groups A and B reported lower close relationship satisfaction and psychological well-being than Group C. Life satisfaction and self-esteem partially mediated the association between family and close relationship satisfaction for all groups. However, this relationship was weaker for Group B, and closeness to family benefitted Group B's life satisfaction to a lesser extent, indicating that the nuanced relationship with family influenced the sexual minority people with heterosexual identities. We recommend future directions and practices in local research and policy-making.

Ball milling transformed electroplating sludges with different components to spinels for stable electrocatalytic ammonia production under ambient conditions.

Electroplating sludge is classified as hazardous waste, but it is also a potential raw resource since it contains plenty of transition metals. However, the component of electroplating sludge is unstable, which hinders recycling. This work investigates the possibility to synthesize spinels with stable catalytic performances by different electroplating sludges. The obtained catalysts are used in electrocatalytic N2 reduction to produce ammonia. As a result, CuCr2O4, ZnCr2O4, and NiCr2O4 spinels are successfully synthesized by a ball-milling and calcination method. These spinels result in ammonia yields of 7.30-8.86 µg h-1 mg-1cat. Among the three spinels, CuCr2O4 shows the highest yield of 8.86 µg h-1 mg-1cat at -0.9 V. Its faradaic efficiency reaches 0.57%. In addition, no by-product N2H4 is detected, indicating a high selectivity. The catalytic process is carried out by both distal and alternating pathways, in which metal doping and oxygen vacancy function as binding sites for N2 adsorption and reduction. Above results indicate that electroplating sludges with unstable components are feasible to produce spinels for stable electrocatalytic ammonia production under ambient temperature. This is in favor of high-value-added utilization of hazardous waste, and devotes to circular economy.

The Impact of Team Knowledge Heterogeneity on Entrepreneurial Opportunity Identification: A Moderated Mediation Model.

PURPOSE: Due to the low success rate of entrepreneurship, the correct identification of entrepreneurial opportunities is one of the important concerns in the field of entrepreneurship research. Therefore, this study focuses on the influence mechanism of entrepreneurial opportunity identification, so as to enrich the influence path of entrepreneurial opportunity identification and provide suggestions for improving the success rate of entrepreneurship. METHODS: After screening and judging the quality of the questionnaires, the valid questionnaires were numbered and matched with 106 team samples. The researchers carried out telephone communication with participants to ask for their attendance, and then took samples on-site at the appointed time and place. RESULTS: The results show that: (1) team knowledge heterogeneity has a significant positive impact on entrepreneurial opportunity identification. (2) Social capital plays a mediating role between team knowledge heterogeneity and entrepreneurial opportunity identification. (3) Promotional regulatory focus, a type of regulation that tends to adopt a radical approach to achieve goals, positively moderates the mediating effect of team knowledge heterogeneity on entrepreneurial opportunity identification through social capital. However, preventive regulatory focus, a type of regulation that tends to adopt a cautious and vigilant way to achieve goals, has no moderating effect. DISCUSSION: In order to improve the correct identification of entrepreneurial opportunities, it is necessary to establish team with knowledge heterogeneity rationally and excavate different levels of social capital behind heterogeneous members. In addition, it also reveals that team style can retain certain promotive in the process of entrepreneurship, which is conducive to the feasibility and profitability of entrepreneurial opportunity identification.

Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-ß/Smad Signaling.

BACKGROUND: Troponin C-1 (TNNC1) has been previously characterized as an oncogenic gene. AIMS: This study aimed to reveal the roles of TNNC1 in gastric cancer and the potential underlying mechanisms. METHODS: TNNC1 siRNAs and TNNC1 overexpression plasmid were used to alter its expression in AGS, MKN45, and HGC-27 cells. CCK-8 assay, colony formation, EdU assay, flow cytometry, transwell assay, and scratch test were conducted to measure the phenotype changes. In vivo effects of TNNC1 silence were confirmed by using a xenograft mouse model. Bioinformatics analysis was conducted to screen out the transcription factor and downstream signaling of TNNC1. RESULTS: TNNC1 was highly expressed in gastric cancer tissues and cell lines, and its expression was associated with poor prognosis. TNNC1 silence suppressed the proliferation, migration, and invasion of AGS and MKN45 cells. However, TNNC1 silence induced apoptosis by mediating the cleavage of caspase-3 and caspase-9. Overexpression of TNNC1 in HGC-27 cells led to the contrary effects. The anti-tumor effects of TNNC1 silence were also confirmed in a xenograft animal model. E2F1 was validated as an upstream transcription factor of TNNC1. Effects of TNNC1 silence on AGS cell migration and invasion were attenuated by E2F1 overexpression. Besides, TGF-ß/Smad was a downstream signaling pathway of TNNC1. The anti-tumor impacts of TNNC1 silence were weaken by SB431542 (a specific inhibitor of TGF-ß signaling) while accelerated by TGF-ß. CONCLUSION: TNNC1 activated by E2F1 functioned as an oncogenic gene through regulating TGF-ß/Smad signaling. TNNC1 was suggested as a potential molecular drug target of gastric cancer.

Hydrodynamics Regulate Longitudinal Plankton Community Structure in an Alpine Cascade Reservoir System.

Previous studies report significant changes on biotic communities caused by cascade reservoir construction. However, factors regulating the spatial-temporal plankton patterns in alpine cascade reservoir systems have not been fully explored. The current study explored effects of environmental factors on the longitudinal plankton patterns, through a 5-year-long study on the environmental factors and communities of phytoplankton and zooplankton in an alpine cascade reservoir system located upstream of Yellow River region. The findings showed that phytoplankton and zooplankton species numbers in the studied cascade reservoir system were mainly regulated by the hydrological regime, whereas nutrient conditions did not significantly affect the number of species. Abundance and biovolume of phytoplankton in cascade reservoirs were modulated by the hydrological regime and nutrient conditions. The drainage rate, N:P ratio, and sediment content in cascade reservoirs were negatively correlated with abundance and biovolume of phytoplankton. Abundance and biovolume of zooplankton were not significantly correlated with the hydrological regime but showed a strong positive correlation with nutrient conditions in cascade reservoirs. Shannon-Wiener index (H') and the Pielou index (J) of phytoplankton were mainly regulated by the hydrological regime factors, such as drainage rate and sediment content in cascade reservoirs. However, temperature and nutrient conditions were the main factors that regulated the Shannon-Wiener index (H') and the Pielou index (J) of zooplankton. Species number, abundance, and biovolume of phytoplankton showed a significant positive correlation with those of zooplankton. Hydrodynamics and nutrient conditions contributed differently in regulating community structure of phytoplankton or zooplankton. These findings provide an understanding of factors that modulate longitudinal plankton community patterns in cascade reservoir systems.

miR-33a-5p inhibits the progression of esophageal cancer through the DKK1-mediated Wnt/ß-catenin pathway.

Esophageal cancer (EC) is one of the most lethal malignancies in humans, and multiple miRNAs have been identified to modulate EC progression by targeting different targets. However, the effect and related mechanism of microRNA-33a-5p (miR-33a-5p) on EC development remain elusive. In this study, we explored the clinical value, function, and possible mechanism of miR-33a-5p in EC. We uncovered that miR-33a-5p and DKK1 are involved in the progression of EC. Significantly, the expression levels of miR-33a-5p were reduced and DKK1 levels were elevated in serum and tissues of clinical EC samples and in EC cell lines. The downregulation of miR-33a-5p and DKK1 upregulation were related to high TNM staging and poor differentiation of patients. The area under the curves (AUCs) of miR-33a-5p and DKK1 for the occurrence of EC were 0.914 and 0.900, respectively. Down-regulation of miR-33a-5p or overexpression of DKK1 indicated a worse prognosis. The miR-33a-5p overexpression or DKK1 depletion induced apoptosis and repressed proliferation, migration, and invasion of EC cells. The repression of miR-33a-5p by inhibitor or DKK1 overexpression presented the conversed effects on EC cells. Mechanically, miR-33a-5p suppressed DKK1 expression, and miR-33a-5p targeted DKK1 to affect the biological behavior of EC through the Wnt/ß-catenin pathway. Meanwhile, miR-33a-5p inhibited the tumor growth of EC in vivo. Thus, we concluded that miR-33a-5p inhibited the progression of EC through the DKK1-mediated Wnt/ß-catenin pathway. MiR-33a-5p and DKK1 can be used as potential therapeutic targets of EC.

Enhanced ultra-wide NIR fluorescence in tellurite glass doped with Er3+-Tm3+-Nd3+-Ag NPs.

Tellurite glasses with combination of Er3+/Tm3+/Nd3+ ions and silver nanoparticles (Ag NPs) were prepared by using single-step melt-quenching technology, and the enhanced effect of Ag NPs on the ultra-broadband near-infrared (NIR) fluorescence was studied. Under the 808 nm LD excitation, two ultra-broadband NIR fluorescence of 1300-1600 nm and 1600-2100 nm underwent an obvious enhancement of about 52% compared to the tri-doping tellurite glass free of Ag NPs. The intensified local electric field induced by Ag NPs together with the energy transfer from Ag species to doped ions is responsible for this enhancement. The enhanced ultra-broadband NIR fluorescence of 1300-1600 nm with the full width at half maximum (FWHM) of 230 nm, originating from the spectral overlapping of 1.34 µm (4F3/2→4I13/2 of Nd3+), 1.47 µm (3H4→3F4 of Tm3+) and 1.53 µm (4I13/2→4I15/2 of Er3+) three bands, is promising in developing new ultra-broadband photonic devices such as fiber amplifiers and tunable lasers.

A novel TSC1 frameshift mutation c.1550_1551del causes tuberous sclerosis complex by aberrant splicing and nonsense-mediated mRNA degradation (NMD) simultaneously in a Chinese family.

BACKGROUND: Tuberous sclerosis complex (TSC), belongs to autosomal dominant genetic disorder, which affects multiple organ systems in the body, including the skin, brain, lungs, kidneys, liver, and eyes. Mutations in TSC1 or TSC2 was proved to be associated with these conditions. METHODS: Gene-panel Sequence of NGS was used to detect the mutation in a Chinese family. The research further investigates whether aberrant splicing and nonsense-mediated mRNA degradation (NMD) could serve as a mechanism cause by TSC1 mutation. MINI-Gene assay apply by pcMINI-TSC1wt/mut plasmids delivered in HeLa and 293T cell lines. Recombinant plasmids expressing wild-type and mutant-type EGFP-TSC1 were constructed and transiently transfected into human embryonic kidney cells 293T by lipofectamine. Real-time PCR and Western Blot were performed to analyze the expression of mRNAs and proteins of EGFP-TSC1 and NMD factor UPF1. RESULTS: The gene test verified a novel heterozygous TSC1 frameshift mutation (TSC1 c.1550_1551del) in the proband and her mother. From MINI-Gene assay, the agarose gel showed that both the mutant and wild-type mRNA possess two main bands, indicating two splicing modes, named band A and B, respectively. The mutation c.1550_1551del has not produced new splicing site, but there is a selective splicing in varying degree significantly after mutation. On the contrary, function validation assay showed that cells transfected with the mutant TSC1 plasmids expressed significantly lower TSC1 in mRNAs and proteins levels, compared with the wild-type TSC1 plasmid transfection. A translation inhibitor cycloheximide and small interfering RNA of UPF1 (siRNA-UPF1) increased mRNA or protein expression of TSC1 significantly in cells transfected with the mutant plasmids. CONCLUSION: Our study demonstrated that the novel TSC1 frameshift mutation (TSC1 c.1550_1551del) trigger aberrant splicing and NMD simultaneously, causing decrease of hamartin, then, leading to tuberous sclerosis complex formation.

miR-133 inhibits proliferation and promotes apoptosis by targeting LASP1 in lupus nephritis.

Lupus nephritis (LN) is a chronic autoimmune disease. Recently, microRNA (miR)-133 has been demonstrated to play an important role in renal cell carcinoma. Our current study was designed to test the role of miR-133 and its potential target in LN. First, significant correlation of LASP1 and miR-133 levels was observed in the human LN tissue. Modification of miR-133 level in the human mesangial cells (HMCs) by either overexpression or knockdown demonstrated a suppressive role of miR-133 in cell proliferation and an inductive role in cell apoptosis. Modification of LASP1 level in the HMCs demonstrated the opposing effects of LASP1 to miR-133 on proliferation and apoptosis. In addition, luciferase assay showed miR-133 directly regulates LASP1 expression through its binding site in the 3'UTR of LASP1. At last, our data showed that the changes in properties, such as suppression in proliferation and induction in apoptosis, induced by overexpression of miR-133 were restored by additional expression of LASP1. In summary, our obtained data demonstrated that miR-133 suppresses proliferation and promotes apoptosis through its binding with LASP1 in human mesangial cells. This study revealed a new mechanism involving the interaction of miR-133 and LASP1 in the pathogenesis of LN.

Gender Role Characteristics and Entrepreneurial Self-Efficacy: A Comparative Study of Female and Male Entrepreneurs in China.

This study, based on Bem's (1974) gender schema theory, investigates gender differences in and the relationship between gender role characteristics and entrepreneurial self-efficacy (ESE) of 261 female and 265 male entrepreneurs in China. The results show that male and female entrepreneurs did not differ significantly in ESE or in masculine gender role characteristics, but differed significantly in feminine gender role characteristics. Examining four different stages in the entrepreneurial life cycle, we find that for female entrepreneurs, feminine characteristics had a positive influence on ESE in the searching and planning stages of entrepreneurship, and masculine characteristics had a positive influence on ESE in the searching stage. For male entrepreneurs, feminine characteristics had a positive influence on ESE in the searching and planning stages, and masculine characteristics had a positive influence on ESE in the marshaling and implementing stages. In addition, one feminine characteristic, "Friendly," showed a positive association with male entrepreneurs' ESE in the marshaling stage. Overall, the feminine gender role factor of "Friendly" and the masculine gender role factor of "Compete" played a greater role on ESE than other characteristics. Implications of the findings are discussed. This study contributes a new perspective to extant research on entrepreneurial self-efficacy and female entrepreneurship.

Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2h4 Mice.

Background: There is growing evidence that sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite synthesized intracellularly by two closely related sphingosine kinases (SphKs), SphK1 and SphK2, is involved in inflammation. However, the role of SphKs/S1P/S1P receptors (S1PRs) in autoimmune thyroiditis (AIT) has not been studied to date. Methods: This study examined whether SphK1/S1P/S1PR1 signaling is aberrantly altered in thyroid tissues and serum of both AIT patients and a spontaneously autoimmune thyroiditis (SAT) mouse model. Murine CD4+T cells were employed to further investigate the downstream signaling of SphK1/S1P/S1PR1. Furthermore, a total of 102 NOD.H-2h4 mice, randomly divided into different groups, were used to investigate the therapeutic effect of S1PR1 blockade and its potential mechanism. Results: We found that components of the SphK1/S1P/S1PR1 pathway were abnormally expressed in patients with Hashimoto thyroiditis and in a SAT mouse model. In addition, S1P could activate signal transducer and activator of transcription 3 (STAT3) through S1PR1 and its downstream signaling pathways in CD4+T cells of NOD.H-2h4 mice. Furthermore, an in vivo study demonstrated that blocking S1PR1 by FTY720 administration could reduce the incidence and severity of thyroiditis and goiter in SAT mice in a time-dependent manner. The proportions of STAT3-related and inflammation-related cell subtypes, such as T helper 1, T helper 17, and follicular T helper cells, were elevated in the SAT group when compared to the control group, and these cell subtypes decreased after FTY720 administration. Furthermore, the downstream inflammatory cytokines of STAT3 were also downregulated after FTY720 administration. Conclusion: The present study shows that blocking Sphk1/S1P/S1PR1 signaling can ameliorate the severity of AIT, providing evidence of a promising therapeutic target for AIT.

Erratum: Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer's disease.

[This corrects the article DOI: 10.3892/etm.2017.5620.].