Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+ T Cell-Related Immune Genes.

Objective: Triple-negative breast cancer (TNBC) poses a significant challenge for treatment efficacy. CD8+ T cells, which are pivotal immune cells, can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology. By leveraging these genes, our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy. Methods: Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases. In the initial stage, we identified 67 differentially expressed genes associated with immune response in CD8+ T cells. Subsequently, we narrowed our focus to three key genes, namely CXCL13, GBP2, and GZMB, which were used to construct a prognostic model. The accuracy of the model was assessed using the validation set data and receiver operating characteristic (ROC) curves. Furthermore, we employed various methods, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, and correlation analyses with CD274 (PD-L1) to explore the model's predictive efficacy in immunotherapeutic responses. Additionally, we investigated the potential underlying biological pathways that contribute to divergent treatment responses. Results: We successfully developed a model capable of predicting the prognosis of patients with TNBC. The areas under the curve (AUC) values for the 1-, 3-, and 5-year survival predictions were 0.618, 0.652, and 0.826, respectively. Employing this risk model, we stratified the samples into high- and low-risk groups. Through KEGG enrichment analysis, we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism, whereas the low-risk group demonstrated significant enrichment in cytokine pathways. Furthermore, immune landscape analysis revealed noteworthy variations between (PD-L1) expression and risk scores, indicating that our model effectively predicted the response of patients to immune-based treatments. Conclusion: Our study demonstrates the potential of CXCL13, GBP2, and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC. These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Interaction effect of midday napping duration and depressive symptoms on subjective memory impairment among older people in China: evidence from the China health and retirement longitudinal study database.

BACKGROUND: Subjective memory impairment (SMI) is common in older people. The aim of this study was to investigate the factors influencing SMI among older people in China, with specific focus on the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. METHODS: Using a dataset representative of the Chinese population from a longitudinal study of health and retirement in China, subjects with SMI were screened using the question "how do you feel about your memory now?" and the Mini-Mental State Examination. A logistic regression model was applied to explore the factors affecting SMI. Additive and multiplicative models were used to analyze the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. RESULTS: We enrolled 8,254 subjects included and the incidence of SMI was 63.9%. Depressive symptoms, nap time, and physical activity were influencing factors of SMI. Midday napping duration and depressive symptoms had positive additive interaction effects on the risk of SMI. When extended-length naps and depressive symptoms coexisted, the risk of SMI was 1.06 times greater than that for either alone (RERI, relative excess risk due to interaction = 0.27, 95% CI = 0.07-0.43; AP, attributable proportion = 0.14, 95% CI = 0.01-0.23; S, synergy index = 1.06, 95% CI = 0.57-1.62). When short naps and depressive symptoms coexisted, the risk of SMI was 1.2 times higher than that for either alone (RERI = 0.12, 95% CI=-0.14-0.39; AP = 0.13, 95% CI=-0.07-0.22; S = 1.20, 95% CI = 0.79-1.82). LIMITATIONS: Since this was a cross-sectional study, the cause-and-effect relationships between the associated variables cannot be inferred. CONCLUSIONS: The interaction effect that exists between nap time and depressive symptoms in older people is important for the identification and early intervention of people at risk for SMI.

Development and validation of a risk prediction model for frailty in patients with diabetes.

BACKGROUND: Frailty is the third most common complication of diabetes after macrovascular and microvascular complications. The aim of this study was to develop a validated risk prediction model for frailty in patients with diabetes. METHODS: The research used data from the China Health and Retirement Longitudinal Study (CHARLS), a dataset representative of the Chinese population. Twenty-five indicators, including socio-demographic variables, behavioral factors, health status, and mental health parameters, were analyzed in this study. The study cohort was randomly divided into a training set and a validation set at a ratio of 70 to 30%. LASSO regression analysis was used to screen the variables for the best predictors of the model based on a 10-fold cross-validation. The logistic regression model was applied to explore the associated factors of frailty in patients with diabetes. A nomogram was constructed to develop the prediction model. Calibration curves were applied to evaluate the accuracy of the nomogram model. The area under the receiver operating characteristic curve and decision curve analysis were conducted to assess predictive performance. RESULTS: One thousand four hundred thirty-six patients with diabetes from the CHARLS database collected in 2013 (n = 793) and 2015 (n = 643) were included in the final analysis. A total of 145 (10.9%) had frailty symptoms. Multivariate logistic regression analysis showed that marital status, activities of daily living, waist circumference, cognitive function, grip strength, social activity, and depression as predictors of frailty in people with diabetes. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The AUC values of the predictive model and the internal validation set were 0.912 (95%CI 0.887-0.937) and 0.881 (95% CI 0.829-0.934). Hosmer-Lemeshow test values were P = 0.824 and P = 0.608 (both > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA indicated that the nomogram had a good predictive performance. CONCLUSIONS: Comprehensive nomogram constructed in this study was a promising and convenient tool to evaluate the risk of frailty in patients with diabetes, and contributed clinicians to screening the high-risk population.

Association between bidirectional intergenerational support and successful aging in China: Evidence from CHARLS 2018.

Aging has gradually accelerated in China, and achieving successful aging of older adults has become a public health concern. Intergenerational support is crucial for Chinese older adults in later life due to the culture of filial piety. However, the association between successful aging and intergenerational support remains poorly understood in China. This study aimed to examine the association between patterns of intergenerational support and successful aging of older adults in China. The present study is a secondary analysis of data obtained from the follow-up survey of the China Health and Retirement Longitudinal Study 2018. Data were analyzed using descriptive statistics and logistic regressions. Bidirectional intergenerational support was associated with successful aging in the participants. In addition, there was an association between different intergenerational financial, caring, and emotional support patterns and elements of successful aging.

Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3ß and Nrf2/NQO1 pathways.

Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3ß (p-GSK3ß) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3ß and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

Structural characterization and protective effect against renal fibrosis of polysaccharide from Ligustrum lucidum Ait.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a traditional Chinese medicine that has been used for tonifying the kidney and liver for decades. AIM OF THE STUDY: This study aimed to explore and identify polysaccharides from FLL and elucidate its protective effect against renal fibrosis. MATERIALS AND METHODS: Polysaccharides were extracted and isolated from FLL. The purified fraction was identified by serial phytochemical work, such as gel-permeation chromatography, ion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance. Mice with unilateral ureteral obstruction (UUO) were applied as a renal fibrosis model. The male UUO mice were pretreated with heteropolysaccharide (Poly) 1 week prior to surgery and continuously treated for 7 days after the operation. Renal fibrosis was assessed by Periodic Acid-Schiff (PAS) staining and Masson's trichrome staining in paraffin-embedded slides. The murine mesangial cells SV40-MES13 upon angiotensin II (Ang II) treatment were developed as an in vitro fibrotic model. The cells were treated by Poly in the presence of Ang II. Molecular expression was detected by RT-PCR, immunoblotting, and immunofluorescence staining. RESULTS: We identified a heteropolysaccharide composed of arabinose and galactose (molar ratio, 0.73:0.27) with a predicted chemical structure characterized by a backbone composed of 1,5-α-Araf, 1,3,5-α-Araf, 1,6-α-Galp, and 1,3,6-ß-Galp and side chains comprised of T-α-Araf, T-α-Arap, and 1,3-α-Araf. Pretreatment of UUO mice with Poly effectively alleviated glomerulosclerosis and tubulointerstitial fibrosis. Moreover, Poly pretreatment down-regulated the expression of extracellular matrix (ECM) protein fibronectin (FN), profibrotic factor VEGF, proinflammatory cytokines MCP-1 and Rantes in the obstructed kidney. Similarly, the incubation of SV40-MES13 cells with Poly significantly inhibited Ang II-induced elevation in accumulation and expression level of FN and attenuated Ang II-evoked up-regulation in protein expression of MCP-1 and Rantes. CONCLUSIONS: Our study isolated and identified a naturally occurring heteropolysaccharide in FLL and revealed its potential in protecting the kidneys from fibrosis.

A Study on the Molecular Mechanism of High Altitude Heart Disease in Children.

Objective: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD. Methods: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau. Results: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO. Conclusion: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.

Corrigendum: The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

[This corrects the article DOI: 10.3389/fpsyg.2020.00247.].

Amelioration of Fructus Ligustri Lucidi and its phenol glycosides on hypercalciuria via stimulating PTH1R/PKA/TRPV5 signaling.

BACKGROUND: Our early studies performed on aged rats, ovariectomized (OVX) rats and diabetic mice, indicated the calciotropic role of Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait., in mediating calcium homeostasis which was partially attributed to its stimulation on renal calcium reabsorption. PURPOSE: This study aimed to explicate the underlying molecular mechanism and explore the potential bioactive ingredients in FLL. STUDY DESIGN AND METHODS: The OVX C57BL/6 J mice were orally administered with low (FL, 75 mg/kg), middle (FM, 225 mg/kg) or high (FH, 675 mg/kg) dose of extract of Fructus Ligustri Lucidi for 10 weeks. The biological properties of trabecular bone were measured by micro-CT and H&E staining. The molecular expression was assessed by immunoblotting and immunostaining. The potential active components were identified by cell membrane chromatography (CMC) and explored in renal tubular cells with Fluo-3/AM fluorescent staining to indicate intracellular calcium level. The male mice fed with high calcium diet (1.2% Ca) and orally treated with active components for 3 weeks. RESULTS: Treatment of OVX mice with FLL extract suppressed the elevation in urinary calcium level (FH, 0.081 ± 0.012, vs. OVX, 0.189 ± 0.038 mg/mg), and increased bone mineral density (FH, 62.41 ± 2.57, vs. OVX, 43.72 ± 8.43 mg/ccm) and percentage of trabecular bone area. It also decreased circulating PTH level (FH, 66.69 ± 10.94, vs. OVX, 303.50 ± 26.56 pg/ml) and up-regulated TRPV5 expression in renal cortex of OVX mice as well as enhanced the expression of PTH receptor (PTH1R) and the ratio of p-PKA/PKA. The PKA inhibitor H89 abolished the induction of serum, prepared from rats treated with FLL extract, on PKA/TRPV5 signaling in renal tubular cells. The CMC identified phenol glycosides, including salidroside and oleuropein, which increased intracellular calcium content, promoted expression of PTH1R and TRPV5 and ratio of p-PKA/PKA as well as decreased calcium excretion in urine of mice fed with high calcium diet. CONCLUSION: Salidroside and oleuropein are major ingredients contributing to the anti-hypercalciuria effects of FLL via acting on PTH1R/PKA/TRPV5 signaling in kidney. Further translational research would be required.

Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS.

Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the Tmax of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC0-t of xanthohumol and isoxanthohumol were 138.83 ± 6.03 and 38.77 ± 4.46 ng/ml·h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.

Xanthohumol ameliorates memory impairment and reduces the deposition of ß-amyloid in APP/PS1 mice via regulating the mTOR/LC3II and Bax/Bcl-2 signalling pathways.

OBJECTIVES: Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. METHODS: APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aß in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. KEY FINDINGS: Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1ß levels both in serum and hippocampus. Xanthohumol also significantly reduced Aß deposition in the hippocampus and activated autophagy and anti-apoptotic signals. CONCLUSIONS: Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.

Discussion on the Pathogenesis of Central Precocious Puberty / 中国生物化学与分子生物学报

Precocious puberty (PP) is a common childhood sexual dysplasia. Central precocious puberty (CPP) is a disease in which the hypothalamic-pituitary-gonadal (HPG) axis is activated in early age, leading to the early release of gonadotrophin releasing hormone, the early development of gonads, and the early onset of puberty. The occurrence of puberty is regulated by gene and environment. Current clinical studies have found that gain-of-function mutations in the KISS1 gene, and loss-of-function mutations in KISS1R (also named GPR54), MKRN3 and DLK1 genes are all important single-gene causes of central precocious puberty. KISS1 is a tumor metastasis suppressor gene. KISS1R codes a G protein-coupled receptor which with its ligand, kisspeptin, forms an excitatory neuroregulator system for GnRH secretion. They play a role in the upstream of the HPG axis. MKRN3 is a maternal-imprinted gene. DLK1 is a gene that regulates the growth of cell. They play a role in the downstream of HPG axis. Recently, the incidence of central precocious puberty has become higher and higher, which is related to the excessive exposure of environmental endocrine disruptors (EEDs) due to the continuous development of social economy. A number of investigations have found that children’s exposure to EEDs is significantly related to the incidence of precocious puberty. In humans, these EEDs also affect the metabolism of gut microbes. This paper aims to review the current studies on the single-gene pathogenesis, epigenetics, gut microbiota and environmental factors of central precocious puberty, so as to provide help for the treatment and prevention of this disease.

Psychometric Properties of a Simplified Chinese Version of the Secondary Trauma Questionnaire in a Potentially Traumatized Study Sample.

BACKGROUND: Screening for secondary traumatic stress (STS) is lacking in China. It is unclear whether Western models of STS can be adapted satisfactorily for use in non-Western regions. The 20-item Secondary Trauma Questionnaire (STQ) is a self-report measure of traumatic stress symptoms in individuals who have been influenced indirectly by suicide or violent injury of people important to the respondents. METHODS: Here, we assessed the psychometric properties of a newly developed Chinese version of the STQ in a potentially traumatized sample (N = 875) composed of doctors, nurses, teachers, civic administration staff, and social workers in China. We performed reliability and validity analyses. Subsequently, we split the total sample into two subsamples for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for measurement invariance analyses. RESULTS: The full scale demonstrated good internal consistency (Cronbach's α = 0.95-0.97), convergent validity, discriminant validity, and factorial validity. CFA affirmed a one-factor structure; the configural, metric, scalar, and strict invariances of the STQ were acceptable across genders. CONCLUSION: The present results indicate that the STQ is a reliable and valid self-report assessment for use with potentially traumatized people in China, and further supports the notion that the STQ is amenable to additional future cross-cultural adaptation.

Corrigendum: The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

[This corrects the article DOI: 10.3389/fpsyg.2020.00247.].

Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway.

To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway.

The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

The Depression Anxiety Stress Scale-21 (DASS-21) is an instrument in the assessment of mental health status. The current study recruited 1,532 Chinese hospital workers [74.4% female; mean age = 31.97 (SD = 9.70) years] to examine the reliability, latent structure, and measurement invariance of the DASS-21 between genders. The Cronbach's α values were greater than 0.90 for total score. This study examined four possible models of the DASS-21 using the confirmatory factor analysis (CFA) in Chinese hospital workers. The results from CFA revealed that the latent structure of the DASS-21 in medical staffs is best represented by a one-factor model. Then we used the one-factor model to examine measurement invariance across genders by using a multiple-group categorical CFA. All values of root mean square error approximation (RMSEA) were less than 0.08, all Comparative Fix Index (CFI) and Tucker-Lewis Index values were greater than 0.90, all ΔCFI (changes in CFI) values were less than 0.010, and ΔRMSEA (the changes in RMSEA) were less than 0.015. These findings supported the gender invariance of the DASS-21 among Chinese hospital workers.

Monotropein attenuates oxidative stress via Akt/mTOR-mediated autophagy in osteoblast cells.

Oxidative stress is a crucial pathogenic factor in osteoporosis. Autophagy is a cellular self-digestion process that can selectively remove damaged organelles under oxidative stress, and thus presents a potential therapeutic target against osteoporosis. Monotropein is an iridoid glycoside which can increase osteoblastic bone formation and be applied for medicinal purpose in China. The aim of this work is to investigate whether autophagy participates the protection effects of monotropein in osteoblasts under oxidative stress and the possible mechanism of such involvement. Here, monotropein was capable of inhibiting the H2O2-induced reactive oxygen species generation in osteoblasts. Monotropein induced autophagy and protected osteoblasts from cytotoxic effects of H2O2, as assessed by viability assays, apoptosis and western blotting. Moreover, it significantly attenuated H2O2-evoked oxidative stress as measured by malondialdehyde, catalase, and superoxide dismutase levels. Importantly, monotropein reduced the phosphorylation of protein kinase B (Akt), mammalian target of rapamycin (mTOR) and its two downstream proteins (p70S6K and 4EBP1). The autophagy level increased in osteoblasts treated with monotropein as represented by an increased in both Beclin1 expression and the LC3-II/LC3-I ratio. However, the Akt activator (SC79) and mTOR activator (MHY1485) suppressed the autophagy level induced by monotropein in H2O2-treated cells. Consequently, the antioxidant effects of monotropein were mediated, at least in part, by enhancing autophagy through the Akt/mTOR pathway. These results suggested that monotropein might be a promising candidate for osteoporosis treatment.

Effect of histone H3Ser10 phophorylation on oocyte meiotic in porcine / 医学研究生学报

ObjectiveThe mechanism of histone phosphorylation modification in oocyte meiosis is less studied. This study is designed to investigate the pattern of histone H3 phophorylation and regulation of maturation process in the porcine oocytes.MethodsThe histone H3Ser10 (H3S10) phosphorylation expression was examined on the porcine oocyte meiotic process. The porcine cumulus oocyte complexes (COCs) were divided into four groups, one group was cultured as control group, and the other 3 groups were supplemented with 5, 10, and 30 μmol/L ZM447439, and cultured in vitro for 27 h, respectively, 5, 10, and 30 μmol/L ZM4474349 treatment group. The proportion of each meiotic stage was counted. The phosphorylation pattern of histone H3S10 and the expression level of protein kinase Aurora B were detected at the porcine oocytes.ResultsCompared with histone H3S10 phosphorylation level of oocyte GVBD phase, the MI and AI phases were significantly increased (P<0.05), and H3S10 phosphorylation level of AI phase was remarkedly higher than that of MII phase (P<0.05). Compared with the control group, the proportion of oocytes at the GVBD phase in the 10 and 30 μmol/L ZM4447439 treatment group [(32.14±0.51)%, (95.34±0.59)%]was higher than that of the control group [(2.56±0.03)%, P<0.05], the proportion of oocytes at the MI phase [(66.88±0.13)%, (4.66±0.04)%] significantly decreased than that of the control group [(87.42±0.14)%, P<0.05], and the proportion of oocytes at the AI stage [(1.01±0.03)%, (0.000±0.00)%] significantly decreased compared with the control group[(10.02 ± 0.21)%, P<0.05]. Compared with the control group (0), oocytes H3S10 dephosphorylation modification ratio in the 10 μmol/L and 30 μmol/L ZM4474349 treatment group [(35.2±0.39)%, (95.4±0.65)%]significantly increased (P<0.05). Compared with the control group, the relative expression level of Aurora B in the 10 and 30 μmol/L ZM4447439 treatment group was significantly reduced (P<0.05).ConclusionHstone H3S10 phosphorylation plays arolein the maturation of mammalian oocytes. AuroraB kinase inhibitors (ZM447439) treatment can reduce H3S10 phosphorylation and Aurora B expression level and lead to oocytesmaturation disorder.

Enzymatic synthesis of nucleoside analogues from uridines and vinyl esters in a continuous-flow microreactor.

We achieved the effective controllable regioselective acylation of the primary hydroxyl group of uridine derivatives catalyzed by Lipase TL IM from Thermomyces lanuginosus with excellent conversion and regioselectivity. Various reaction parameters were studied. These regioselective acylations performed in continuous flow microreactors are a proof-of-concept opening the use of enzymatic microreactors in uridine derivative biotransformations.