The early career resilience experience of generation Z newly graduated registered nurses in standardized training in the emergency department: a qualitative study in Shanghai.

BACKGROUND: The period of standardized training is a transitional stage when Generation Z newly graduated registered nurses (Gen Z NGRNs) change their role from student to nurse. Affected by the COVID-19, they lack clinical practice and practicum experience in emergency departments in their university studies. At the beginning of career, they are under great pressure. Resilience is one of the factors that reduce their stress level and increases endurance. It is of interest to understand how this representative group of nurses gained and played the experience of resilience early in their careers. OBJECTIVE: To explore Gen Z NGRNs' experience and process of resilience, to provide a new perspective and theoretical basis for psychological rehabilitation or intervention of medical staff who experienced transition shock. METHODS: This study employed a qualitative design based on the phenomenological approach. 18 nurses from a third-level class-A hospital in Shanghai who participated in standardized training in emergency department were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation. RESULTS: The investigation uncovered three themes and ten subthemes. Pressure and challenge contained high workload and high risk coexist, death's stress response, more emergencies and high professional requirements. Coping and adaptation contained team help, psychological restructuring, peer support, transformational leadership. Reflection and planning contained enhance learning, appreciate life. CONCLUSIONS: Our study described the embodiment and coping experience of the physical and mental stress faced by Gen Z NGRNs during their standardized training in the emergency department. It is emphasized that nurse educators should pay attention to the character and actual needs of Gen Z NGRNs, explore and formulate strategies, so as to guide NGRNs to quickly adapt and grow in the new role. The ultimate goal is to increase nurse retention and improve the quality of nursing.

Correlation analysis between occupational stress and metabolic syndrome in workers of a petrochemical enterprise: based on two assessment models of occupational stress.

BACKGROUND: Occupational stress is becoming a common phenomenon around the world. Being in a high occupational stress state for a long time may destroy the metabolic balance of the body, thereby increasing the risk of metabolic diseases. There is limited evidence regarding the correlation between occupational stress and metabolic syndrome (MetS), particularly in the petrochemical workers. METHODS: A total of 1683 workers of a petrochemical enterprise in China were included in the survey by cluster sampling method. The occupational stress assessment was carried out by the Job Content Questionnaire and the Effort-Reward Imbalance Questionnaire, and the general demographic characteristics, work characteristics, occupational hazards, lifestyle and health examination data of the participants were collected. Logistic regression and multiple linear regression were used to analyze the correlations and influencing factors between occupational stress and its dimensions with MetS and its components. RESULTS: A total of 1683 questionnaires were sent out, and 1608 were effectively collected, with an effective recovery rate of 95.54%. The detection rates of occupational stress in Job Demand-Control (JDC) and Effort-Reward Imbalance (ERI) models were 28.4% and 27.2%, respectively. In this study, 257 participants (16.0%) were diagnosed with MetS. Compared with the non-MetS group, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG) and fasting blood-glucose (FBG) levels were significantly higher in the MetS group, and high density lipoprotein-cholesterol (HDL-C) levels were significantly lower (P < 0.001). The results of multiple linear regression showed that after adjusting for nation, marital status, education, work system, smoking and drinking, and further adjusting for occupational hazards, the D/C ratio was significantly negatively correlated with SBP in the JDC model. Social support was negatively correlated with WC. In the ERI model, there was a significant positive correlation between over-commitment and FBG. CONCLUSIONS: The detection rates of occupational stress and MetS were high in workers of a petrochemical enterprise. In the JDC model, occupational stress was negatively correlated with SBP, and social support was negatively correlated with WC. In the ERI model, there was a significantly positive correlation between over-commitment and FBG.

The value of FDG combined with PiB PET in the diagnosis of patients with cognitive impairment in a memory clinic.

AIMS: To analyze the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with amyloid PET in cognitive impairment diagnosis. METHODS: A total of 187 patients with dementia or mild cognitive impairment (MCI) who underwent 11 C-Pittsburgh compound B (PiB) and FDG PET scans in a memory clinic were included in the final analysis. RESULTS: Amyloid-positive and amyloid-negative dementia patient groups showed a significant difference in the proportion of individuals presenting temporoparietal cortex (p < 0.001) and posterior cingulate/precuneus cortex (p < 0.001) hypometabolism. The sensitivity and specificity of this hypometabolic pattern for identifying amyloid pathology were 72.61% and 77.97%, respectively, in patients clinically diagnosed with AD and 60.87% and 76.19%, respectively, in patients with MCI. The initial diagnosis was changed in 32.17% of patients with dementia after considering both PiB and FDG results. There was a significant difference in both the proportion of patients showing the hypometabolic pattern and PiB positivity between dementia conversion patients and patients with a stable diagnosis of MCI (p < 0.05). CONCLUSION: Temporoparietal and posterior cingulate/precuneus cortex hypometabolism on FDG PET suggested amyloid pathology in patients with cognitive impairment and is helpful in diagnostic decision-making and predicting AD dementia conversion from MCI, particularly when combined with amyloid PET.

Functional analysis of polymorphism haplotypes of MGMT in residents of high background radiation area.

To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a D' of 0.928 (r2 = 0.581) for -808 T>C and -19 C>T, 0.928 (r2 = 0.581) for -797 G>A and -19 C>T in Han Chinese HBRA residents. Complete LD with a D' of 1.0 (r2 = 1.0) was observed between -808 T>C and -797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (-637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying -19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the -19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.

Analysis of occupational stress and its correlation with oxidative-antioxidant levels among employees of a power grid enterprise in Guangdong.

BACKGROUND: Occupational stress and its health effects on occupational populations have attracted extensive attention from researchers in public health. The stressors faced by employees of power grid enterprises are increasing progressively, which is easy to cause occupational stress. The balance of the body's oxidative-antioxidant levels plays an essential role in maintaining the body's health status. This study aims to explore occupational stress and its correlation with oxidative-antioxidant levels in employees of a power grid enterprise. METHODS: A cluster random sampling method was used to investigate the basic information of 528 employees in a power grid enterprise and investigate the two occupational stress models of employees by using the Job Content Questionnaire based on the job demand-control-support (JDC) model, and the Effort-Reward Imbalance Questionnaire based on the effort-reward imbalance (ERI) model, respectively. Peripheral blood samples were collected from the employees to measure the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD). The correlation between different models of occupational stress level and the body's oxidation-antioxidation level was further explored. RESULTS: The detection rate of high JDC model occupational stress was 50.6% and the detection rate of high ERI model occupational stress was 50.9%. The JDC model occupational stress was significantly associated with high-temperature and high-altitude operation, visual display terminal operation, monthly income, and exercise (all P < 0.05). The ERI model occupational stress was significantly associated with visual display terminal operation (all P < 0.05). The results of the generalized additive model showed that SOD levels had a non-linear relationship with the D/C ratio as well as the E/R ratio. With the D/C ratio close to 1, SOD levels raised rapidly. When the E/R ratio exceeded 1, the SOD level raised rapidly (all P<0.05) . TAC levels were negatively associated with the E/R ratio (P < 0.05). CONCLUSION: The detection rates of occupational stress in both models among employees in a power grid enterprise are higher. ERI model occupational stress was associated with body TAC and SOD levels, and JDC model occupational stress was associated with body SOD levels.

A Validation Study of the Hong Kong Brief Cognitive Test for Screening Patients with Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The Hong Kong Brief Cognitive Test (HKBC), a brief instrument designed to screen for cognitive impairment in older adults, has been validated in Cantonese-speaking populations and has shown better performance than the Mini-Mental State Examination (MMSE) in detecting both mild and major neurocognitive disorder (NCD). OBJECTIVE: This study aimed to validate the HKBC for detecting patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) in a Mandarin-speaking Chinese population. METHODS: Two hundred forty-eight patients with aMCI, 67 patients with mild AD and 306 healthy controls (HCs) were recruited for this study and completed both the HKBC and the MMSE. The performance of the HKBC and MMSE in distinguishing patients with aMCI from HCs and distinguishing patients with AD from patients with aMCI was compared in the whole population and in age- and education-stratified subgroups. RESULTS: The optimal HKBC cutoff score for distinguishing patients with aMCI from HCs was 23, and the optimal cutoff score for distinguishing patients with AD from patients with aMCI was 17. The HKBC significantly outperformed the MMSE at differentiating patients with aMCI from HCs in the whole population (z = 12.38, p < 0.01) and all subgroups stratified by age or education. Regarding the discrimination of patients with AD from patients with aMCI, the HKBC showed better performance than the MMSE in the oldest subgroup (z = 2.18, p = 0.03). CONCLUSION: The HKBC is a sensitive and specific screening tool for detecting aMCI and AD in the Chinese population across age groups and educational levels.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Paired box 8 facilitates the c-MYC related cell cycle progress in TP53-mutation uterine corpus endometrial carcinoma through interaction with DDX5.

As a molecular marker of the female reproductive system, Paired Box 8 is widely used in pathological diagnosis of gynecological tumors, but it is not clear whether its expression level is related to the development of uterine corpus endometrial carcinoma and molecular subtype classifications. Here, we show that PAX8 is up-regulated in TP53 mutation category of UCEC, which is result from the low methylation level of PAX8 in UCEC. We have identified that genes connected to ribosome, lysosome, ribosome biogenesis and cell cycle as PAX8 targets and demonstrate that modulation of the PAX8-DDX5 interaction influences c-MYC related cell cycle and cell growth. Our work defines DDX5 as a critical PAX8 co-factor, places the PAX8-DDX5 interaction in biological context, and highlights PAX8 as a key point for development of novel anti-MYC therapies in TP53-mutation UCEC.

Dynamic analysis and application in medical digital image watermarking of a new multi-scroll neural network with quartic nonlinear memristor.

Memristor is widely used in various neural bionic models because of its excellent characteristics in biological neural activity simulation. In this paper, a piecewise nonlinear function is used to transform the quartic memristor, which is introduced into the ternary Hopfield neural network (HNN) with self-feedback, and a piecewise quartic memristive chaotic neural network model with multi-scroll is constructed. Through simulation analysis, the number of scroll layers changes with memristor parameters and has significant coexistence of multi-scroll attractors and high initial value sensitivity has been found. Using its excellent unpredictability, a digital watermarking algorithm based on wavelet transform is improved and used in the protection of personal medical data. The results show that it not only improves the confidentiality and convenience, but also ensures its robustness and has good encryption effect.

ATM and TP53 polymorphisms modified susceptibility to radiation-induced lens opacity in natural high background radiation area, China.

Purpose: A population-based case-control study was conducted in Yangjiang and Enping areas in South China to assess whether the risk of lens opacity induced by natural high background radiation exposure is modulated by polymorphisms of ATM and TP53.Materials and methods: A total of 133 cases who were diagnosed with cortical and posterior subcapsular (PSC) opacity were recruited, and 419 healthy controls were selected through counter-matching in terms of radiation status. Genomic DNA from all the participants was genotyped with the Illumina platform for four single nucleotide polymorphisms of ATM (rs189037, rs373759, and rs4585) and TP53 (rs1042522). The cumulative lens dose received during the entire life was estimated based on annual indoor and outdoor radiation doses and gender- and age-specific occupancy factors. Non-conditional logistic regression was performed to calculate odds ratio (OR) and 95% confidence intervals (95% CI).Results:ATM rs189037 and TP53 rs1042522 were significantly related to cortical and PSC opacity. The risk of opacity was higher when individuals carried the A allele of ATM rs189037 and C allele of TP53 rs1042522, compared with GG genotype. ATM rs189037 A allele carriers (AG/AA) and TP53 rs1042522 C allele carriers (CG/CC) combined with a cumulative lens dose of 100 mGy or higher showed statistically significant opacity risks (OR = 5.51, 95% CI: 1.47-20.66; OR = 2.69, 95% CI: 1.10-6.60).Conclusion: The A allele of ATM rs189037 and C allele of TP53 rs1042522 increased the risk of lens opacity induced by radiation. These polymorphisms in ATM and TP53 might modify the risk of cortical and PSC opacity induced by chronic and prolonged low-dose radiation.

CircSAMD11 facilitates progression of cervical cancer via regulating miR-503/SOX4 axis through Wnt/ß-catenin pathway.

Cervical cancer (CC) is a common gynaecological malignant tumour with a high mortality rate. Circular RNAs (circRNAs) play a critical role in tumour occurrence and development. This study aimed to investigate the function and molecular basis of hsa_circ_0009189 (circSAMD11) in CC development. RNA levels were determined by qRT-PCR, and protein expression was measured by western blot. Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometry assays. The relationship between miR-503 and circSAMD11/SOX4 was validated via dual-luciferase reporter assay, RIP or RNA pull-down assay. Xenograft assay was conducted to test tumour growth in vivo. CircSAMD11 and SOX4 levels were elevated, while miR-503 level was reduced in CC tissues and cells. Knockdown of circSAMD11 suppressed CC cell proliferation, migration and invasion and accelerated apoptosis. CircSAMD11 was localised in cytoplasm and directly targeted miR-503. Also, circSAMD11 sponged miR-503 to modulate SOX4 expression. Additionally, circSAMD11 regulated CC progression via absorbing miR-503 or modulating SOX4. Besides, depletion of circSAMD11 hindered tumorigenesis in vivo. CircSAMD11 contributed to CC progression by regulating miR-503/SOX4 signalling and activating Wnt/ß-catenin pathway, which provides a promising therapeutic target for cervical cancer.

High-performance photonic spin Hall effect in anisotropic epsilon-near-zero metamaterials.

A high-performance photonic spin Hall effect is demonstrated in an anisotropic epsilon-near-zero (ENZ) metamaterial based on the wave-vector-varying Pancharatnam-Berry phase. The giant out-of-plane anisotropy of ENZ metamaterial induces strong spin-orbit coupling. With a small incident angle, photons with opposite spins move along opposite transverse directions gradually. After transmitting through a submicrometer thick ENZ metamaterial, the spin photons are fully separated with a spin separation of 2.7 times beam waist and transmittance of 70.1%, allowing a figure of merit F up to 1.9. A practical ENZ metamaterial consisting of an Ag nanorod array is proposed, whose figure of merit is still up to 0.006. This high-performance photonic spin Hall effect provides an integrated and practical way for the development of spin-photonic devices.

Construction of a Cascade Catalyst of Nanocoupled Living Red Blood Cells for Implantable Biofuel Cell.

The broad applications of implantable glucose biofuel cells (GBFCs) have become very attractive in biomedical sciences. The key challenge of GBFCs is eliminating the inevitable product H2O2 generated from the oxidation of glucose when glucose oxidase (GOx) is used as a catalyst while improving the performance of GBFCs. In this work, the cascade electrocatalyst, RBCs@NPDA was obtained through the in situ polymerization of dopamine to form nanopolydopamine (NPDA) on the surface of red blood cells (RBCs). The RBCs@NPDA can catalyze both fuels of H2O2 and O2, so as to generate a high cathodic current (0.414 mA cm-2). Furthermore, when RBCs@NPDA was used as a cathodic catalyst in the membraneless GBFC, it exhibited the cascade catalytic activity in the reduction of O2-H2O2 and minimized the damage to RBCs caused by the high concentration of H2O2. The mechanism research indicates that RBCs@NPDA integrates the property of NPDA and RBCs. Specifically, NPDA plays a catalase-like role in catalyzing the decomposition of H2O2, while RBCs play a laccase-like role in electrocatalyzing the O2 reduction reaction. This work offers the cascade catalyst for improving the performance of implantable GBFC and presents a strategy for constructing catalysts using living cells and nanomaterials to replace deformable and unstable enzymes in other biofuel cells.

miR-149-5p inhibition reduces Alzheimer's disease ß-amyloid generation in 293/APPsw cells by upregulating H4K16ac via KAT8.

Alzheimer's disease (AD), the leading cause of age-related dementia, is characterized by abnormal ß-amyloid accumulation. During learning, memory formation and consolidation, increased levels of histone H3 and H4 acetylation are observed. The present study reported significantly decreased level of H4K16ac in the plasma of patients with AD compared with healthy subjects via western blotting and reverse transcription-quantitative (RT-q)PCR. Lysine acetyltransferase 8 (KAT8) expression, the major lysine acetyltransferase responsible for the acetylation of H4K16, was significantly decreased in patients with AD compared with healthy subjects as determined via western blotting and RT-qPCR. The results indicated that aberrant expression patterns of H4K16ac and KAT8 might be associated with AD progression. Moreover, western blot analysis demonstrated that KAT8-overexpression cells displayed increased levels of H4K16ac, accompanied by higher levels of neuroprotective soluble amyloid precursor protein (sAPP)α and ß-secretase (BACE)2, and decreased levels of sAPPß and BACE1 compared with negative control and vector cells. In neurodegenerative disorders, microRNAs (miRNAs/miRs) are deregulated; however, the effect of miRNA dysregulation on histone acetylation is not completely understood. To the best of our knowledge, the present study identified a novel inhibitory interaction between miR-149-5p and KAT8 3'-UTR that contributed to the pathological alterations in an AD cell model for the first time, using bioinformatics and a dual-luciferase reporter assay. The western blotting results indicated that, compared with the inhibitor control group, miR-149-5p inhibitor markedly increased H4K16ac levels, which were significantly suppressed by co-transfection with KAT8 short hairpin (sh)RNA. KAT8 shRNA and miR-149-5p inhibitor co-transfection abolished the beneficial effects of miR-149-5p inhibitor. The results indicated that miR-149-5p regulated KAT8 and H4K16ac expression in an AD cell model, which may be associated with the pathological process of AD; therefore, miRNA may serve as a potential drug target for AD.

MicroRNA-155 inhibits dengue virus replication by inducing heme oxygenase-1-mediated antiviral interferon responses.

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.

Trans-cinnamaldehyde shows anti-depression effect in the forced swimming test and possible involvement of the endocannabinoid system.

Depression is a mental disease that significantly reduces the quality of patients' life. Around 322 million people of all ages carry the heavy burden of depression on a worldwide scale, with a life-time prevalence of 20% according to the WHO. Trans-cinnamaldehyde (TCA) is an excellent COX-2 inhibitor in central nervous system which is a main constituent of GUIZHI as a member of traditional Chinese herb. Furthermore, previous studies demonstrated that TCA suppressed depression-like behavior in chronic unexpected mild stress, plus maze test and open field test. However, the molecular mechanism of TCA anti-depression effect is not clear. We examined the immobility of TCA pretreated male BALB/c mice in the forced swimming test (FST). Results show that TCA (50 mg/kg, po) revealed a significant effect on reduced immobility in the FST, compared with SAL group which indicated that TCA suppressed depression-like behavior. Moreover, TCA elevated the level of 5-HT and decreased the ratio of Glu/GABA in mice hippocampus. Compared with SAL + FST group, TCA + FST group significantly decreased COX-2, TRPV1 and CB1 protein level in mice hippocampus (p < 0.05, p < 0.05, p < 0.01). These findings suggest that TCA treatment exerted anti-depressive effect and was able to regulate neurotransmitters in the FST. This effect may have positive influence on the endocannabinoid (eCB) system.

Tunable asymmetric spin splitting by black phosphorus sandwiched epsilon-near-zero-metamaterial in the terahertz region.

In-plane photonic spin splitting effect is investigated in tunneling terahertz waves through an epsilon-near-zero metamaterial sandwiched between monolayer black phosphorus (BP). The strong in-plane anisotropy of BP layers will induce in-plane asymmetric spin splitting. The asymmetric spin splitting can be flexibly tuned by the angles between the incident plane and the armchair crystalline directions of the top and bottom BP layers, i.e., ϕ1 and ϕ2. Based on this, an angle-resolved barcode-encryption scheme is discussed. For the special case of ϕ1 = ϕ2 = 0 or 90°, the transmitted beam undergoes Goos-Hänchen shift, which varies with the carrier density of BP. We believe these findings can facilitate the development of novel optoelectronic devices in the Terahertz region.

In Situ Engineering of Intracellular Hemoglobin for Implantable High-Performance Biofuel Cells.

The key challenge for the broad application of implantable biofuel cells (BFCs) is to achieve inorganic-organic composite biocompatibility while improving the activity and selectivity of the catalysts. We have fabricated nanoengineered red blood cells (NERBCs) by an environmentally friendly method by using red blood cells as the raw material and hemoglobin (Hb) embedded with ultrasmall hydroxyapatite (HAP, Ca10 (PO4 )6 (OH)2 ) as the functional BFC cathode material. The NERBCs showed greatly enhanced cell performance with high electrocatalytic activity, stability, and selectivity. The NERBCs maintained the original biological properties of the natural cell, while enhancing the catalytic oxygen reduction reaction (ORR) through the interaction between -OH groups in HAP and the Hb in RBCs. They also enabled direct electron transportation, eliminating the need for an electron-transfer mediator, and showed catalytic inactivity for glucose oxidation, thus potentially enabling the development of separator-free BFCs.

CPEB2-dependent translation of long 3'-UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue.

Expression of mitochondrial proton transporter uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is essential for mammalian thermogenesis. While human UCP1 mRNA exists in a long form only, alternative polyadenylation creates two different isoforms in mice with 10% of UCP1 mRNA found in the long form (Ucp1L) and ~90% in the short form (Ucp1S). We generated a mouse model expressing only Ucp1S and found that it showed impaired thermogenesis due to a 60% drop in UCP1 protein levels, suggesting that Ucp1L is more efficiently translated than Ucp1S. In addition, we found that ß3 adrenergic receptor signaling promoted the translation of mouse Ucp1L and human Ucp1 in a manner dependent on cytoplasmic polyadenylation element binding protein 2 (CPEB2). CPEB2-knockout mice showed reduced UCP1 levels and impaired thermogenesis in BAT, which was rescued by ectopic expression of CPEB2. Hence, long 3'-UTR Ucp1 mRNA translation activated by CPEB2 is likely conserved and important in humans to produce UCP1 for thermogenesis.

Three new C-27-carboxylated-lupane-triterpenoid derivatives from Potentilla discolor Bunge and their in vitro antitumor activities.

Three new lupane-triterpenoids (1-3) along with six known compounds (4-9) were isolated from the ethanolic extract of whole plant of Potentilla discolor Bunge. The structures of Compounds 1-3 were established by extensive 1D and 2D NMR together with other spectrum analysis, indicating that their C-27 positions were highly oxygenated, which were rarely found in nature. Their in vitro anti-proliferative activities against HepG-2, MCF-7 and T-84 cell lines were evaluated by Cell Counting Kit-8 (CCK-8) assay, and the results showed different activities for three cell lines with IC50 values ranging from 17.84 to 40.64 µM. In addition, the results from Hoechst 33258 and AO/EB staining as well as annexinV-FITC assays exhibited Compound 1 caused a markedly increased HepG-2 cellular apoptosis in a dose-dependent manner. The further mechanisms of Compound 1-induced cellular apoptosis were confirmed that 1 induced the production of ROS and the alteration of pro- and anti-apoptotic proteins, which led to the dysfunction of mitochondria and activation of caspase-9 and caspase-3 and finally caused cellular apoptosis. These results would be useful in search for new potential antitumor agents and for developing semisynthetic lupane-triterpenoid derivatives with high antitumor activity.