Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence.

S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear mono-methylation of H3 Lys 9 (H3K9) at the expense of broad losses in histone di- and tri-methylation. Under SAM-depleted conditions, H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide evidence for an adaptive response that enables epigenetic persistence to metabolic stress.

[Association of waist-to-height ratio with sarcopenic obesity in hemodialysis patients with normal body mass index].

Objective: To explore the association between waist-to-height ratio (WHtR) and sarcopenic obesity (SO) in maintenance hemodialysis (MHD) patients with normal body mass index (BMI). Methods: A multicenter and cross-sectional study that included adult patients undergoing MHD was conducted in 20 hemodialysis centers from June 1st to August 30th, 2021. Body composition was evaluated by body composition monitor based on bioimpedance spectroscopy. According to the quartiles of WHtR, patients were divided into four groups: Q1, Q2, Q3 and Q4 group. The association of WHtR with SO was determined by multiple logistic regression models, stratified analyses, interactive analyses, and receiver operating characteristic (ROC) analyses, respectively. Results: A total of 2 207 MHD patients (1 341 males and 866 females) were included, and aged [M (Q1, Q3)] 57 (44, 68) years. The prevalence of SO was increased with increasing quartiles of WHtR [8.6% (46/533), 22.5% (141/628), 35.4% (215/608), and 44.3% (194/438) for Q1, Q2, Q3, and Q4 group, respectively]. Multivariate logistic regression analysis showed that WHtR was associated with SO. The association remained statistically significant even after adjusting for age, gender, dialysis vintage, BMI, biochemical indicators, and various medical histories. Compared with Q1 group, the odds ratios (OR) were 2.54 (95%CI: 1.69-3.83), 4.30 (95%CI: 2.88-6.42) and 5.18 (95%CI: 3.37-7.96) for Q2, Q3 and Q4 group, respectively. The interaction analysis showed that age, sex and history of diabetes had interactive roles in the association between WHtR and SO (all P<0.05). The association stably existed across subgroups, and it was more obvious in male patients, those with older age and without a history of diabetes（all P<0.05）. Furthermore, the cut-off value of WHtR identifying SO in male patients was 0.49, and the corresponding area under the curve (AUC) was 0.73 (95%CI: 0.70-0.75), with the sensitivity of 72.7% and specificity of 60.3%. In female patients, the cut-off value was 0.51, and the AUC was 0.68 (95%CI: 0.65-0.71), with the sensitivity of 70.1% and specificity of 57.8%. Conclusion: WHtR could be used as a simple index to evaluate the risk of SO in MHD patients with normal BMI.

[A survey on the implementation of cardiovascular surgery for congenital heart disease in China between 2017 and 2021].

Objective: To investigate the inplementation of cardiovascular surgery for congenital heart disease (CHD) in China. Methods: A cross-sectional study was carried out. The CHD cardiovascular surgery data collected by the Chinese Society of Extracorporeal Circulation from 2017 to 2021 in 31 provinces (autonomous regions/municipalities) of China were retrospectively reviewed, the implementation of CHD cardiovascular surgery in different provinces, regions, general/specialized hospitals, and different age groups (whether≤18 years old) were summarized, and the correlation analysis between the number of surgeries carried out in each province/region and the gross regional product and the number of the regional population was performed. Results: Between 2017 and 2021, the annual volume of CHD cardiovascular surgery was 77 120, 77 634, 81 161, 62 663 and 71 492, respectively, showing a decreasing trend. Meanwhile, the proportion of CHD patients aged≤18 years who underwent cardiovascular surgery also showed a downward trend, from 79.8% (61 557/77 120) in 2017 to 58.6% (41 871/71 492) in 2021 (P=0.027). The number of surgical cases varied greatly among different provinces, including 4 provinces with≥5 000 cases and 9 provinces with 2 000-5 000 cases. In the five years, the number of CHD cardiovascular surgeries in Central and East China was the largest, accounting for 41.1%-45.5% of the total surgical cases. The proportion of CHD surgery cases≤18 years old was the highest in Southwest China (69.7%-87.4%) and the lowest in Northeast China (28.2%-68.9%). Except for 2021, the number of cases carried out by each region between 2017 and 2020 was correlated with the gross regional product (r=0.929, 0.929, 0.893 and 0.964, respectively, all P<0.05) and the population (r=0.821, 0.893, 0.821 and 0.857, respectively, all P<0.05). Hospitals that performed more than 100 operations (20.5%±1.2% of the total number of hospitals) completed 86.2%±1.2% of the total number of operations in China during the 5-year period. In 2017 and 2021, the number of CHD cardiovascular surgeries preformed in children's/women's and children's specialized hospitals accounted for 24.3% (18 772/77 120) and 23.8% (17 012/71 492) of the total number of cases in China, respectively. Conclusions: From 2017 to 2021, the number of cardiovascular surgery for CHD decreases slightly, but the proportion of surgery for adult CHD patients increases significantly.There is a strong correlation between the number of CHD operations in each region and their economic development status. The scale of CHD cardiovascular surgery performed in children's hospitals/women's and children's hospitals accounts for about a quarter of the total volume in China.

[Study on construction of c-Met specific CAR-T cells and its killing effect on non-small cell lung carcinoma].

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

Local negative permittivity and topological phase transition in polar skyrmions.

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

MicroRNA-214-3p Ameliorates LPS-Induced Cardiomyocyte Injury by Inhibiting Cathepsin B.

Myocardial injury is a common complication of sepsis. MicroRNA (miRNA) miR-214-3p is protective against myocardial injury caused by sepsis, but its mechanism in lipopolysaccharide (LPS)- induced cardiomyocyte injury is still unclear. An AC16 cell injury model was induced by LPS treatment. Cell Counting Kit-8 and flow cytometry assay showed decreased cell viability and increased apoptosis in LPS-treated AC16 cells. The levels of caspase- 3, Bax, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), myosin 6 (Myh6), myosin 7 (Myh7), reactive oxygen species (ROS), and malondialdehyde (MDA) were increased in LPS-treated AC16 cells, but the levels of Bcl-2 and superoxide dismutase (SOD) were decreased. MiR-214-3p was down-regulated and cathepsin B (CTSB) was upregulated in LPS-treated AC16 cells. At the same time, miR-214-3p could target CTSB and reduce its expression. We also found that a miR-214-3p mimic or CTSB silencing could significantly reduce LPSinduced apoptosis, decrease ROS, MDA, caspase-3, and Bax and increase SOD and Bcl-2. CTSB silencing could significantly reduce ANP, BNP, Myh6, and Myh7 in LPS-treated AC16 cells. The effects of CTSB silencing were reversed by a miR-214-3p inhibitor. In summary, miR-214-3p could inhibit LPSinduced myocardial injury by targeting CTSB, which provides a new idea for myocardial damage caused by sepsis.

Fracture Diodes: Directional Asymmetry of Fracture Toughness.

Toughness describes the ability of a material to resist fracture or crack propagation. It is demonstrated here that fracture toughness of a material can be asymmetric, i.e., the resistance of a medium to a crack propagating from right to left can be significantly different from that to a crack propagating from left to right. Such asymmetry is unknown in natural materials, but we show that it can be built into artificial materials through the proper control of microstructure. This paves the way for control of crack paths and direction, where fracture-when unavoidable-can be guided through predesigned paths to minimize loss of critical components.

Diabetes self-management education exposure and glycated haemoglobin levels among Marshallese participants in a randomized controlled study.

AIMS: A randomized control trial (RCT) of diabetes self-management education (DSME), undertaken by a community-based participatory research (CBPR) partnership between the University of Arkansas for Medical Sciences (UAMS) and the Marshallese community in Arkansas. The RCT examined the effect of hours of intervention exposure, with the hypothesis that increased exposure is one reason the Adapted-Family DSME was found to be more effective than the Standard DSME. METHODS: Some 221 Marshallese with type 2 diabetes were randomized to an Adapted-Family DSME group (in-home setting) (n = 110) or a Standard DMSE group (community setting) (n = 111). The Adapted-Family DSME included 10 h of education that covered the core self-care elements recommended by the American Diabetes Association (ADA) and American Association of Diabetes Educators' (AADE) recommendations. The Standard DSME included 10 h of intervention with all ADA and AADE core elements. RESULTS: The number of hours of intervention exposure in the Adapted-Family DSME arm (mean = 8.0; median = 10.0) was significantly higher than the number of hours of intervention received in the Standard DSME arm (mean = 1.5; median = 0.0). As hypothesized, higher exposure was associated with a significant reduction in HbA1c in a model including only study arm and exposure (P = 0.01), and in a model including study arm, exposure, and all demographic variables (P = 0.046). CONCLUSIONS: This finding is consistent with previous reviews that showed increased exposure to DSME produced improved glycaemic control and ≥ 10 h of DSME produces clinically meaningful reductions in HbA1c .

Rapid data-driven model reduction of nonlinear dynamical systems including chemical reaction networks using ℓ1-regularization.

Large-scale nonlinear dynamical systems, such as models of atmospheric hydrodynamics, chemical reaction networks, and electronic circuits, often involve thousands or more interacting components. In order to identify key components in the complex dynamical system as well as to accelerate simulations, model reduction is often desirable. In this work, we develop a new data-driven method utilizing ℓ1-regularization for model reduction of nonlinear dynamical systems, which involves minimal parameterization and has polynomial-time complexity, allowing it to easily handle large-scale systems with as many as thousands of components in a matter of minutes. A primary objective of our model reduction method is interpretability, that is to identify key components of the dynamical system that contribute to behaviors of interest, rather than just finding an efficient projection of the dynamical system onto lower dimensions. Our method produces a family of reduced models that exhibit a trade-off between model complexity and estimation error. We find empirically that our method chooses reduced models with good extrapolation properties, an important consideration in practical applications. The reduction and extrapolation performance of our method are illustrated by applications to the Lorenz model and chemical reaction rate equations, where performance is found to be competitive with or better than state-of-the-art approaches.

[Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles].

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION: TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

Optimizing the linearity in high-speed photodiodes.

Analog photonic links require high-fidelity, high-speed optical-to-electrical conversion for applications such as radio-over-fiber, synchronization at kilometer-scale facilities, and low-noise electronic signal generation. Photodetector nonlinearity is a particularly vexing problem, causing signal distortion and excess noise, especially in systems utilizing ultrashort optical pulses. Here we show that photodetectors designed for high power handling and high linearity can perform optical-to-electrical conversion of ultrashort optical pulses with unprecedented linearity over a large photocurrent range. We also corroborate and expand upon the physical understanding of how the broadband, complex impedance of the circuit following the photodiode modifies the linearity - in some cases quite significantly. By externally manipulating the circuit impedance, we extend the detector's linear range to higher photocurrents, with over 50 dB rejection of amplitude-to-phase conversion for photocurrents up to 40 mA. This represents a 1000-fold improvement over state-of-the-art photodiodes and significantly extends the attainable microwave power by a factor of four. As such, we eliminate the long-standing requirement in ultrashort pulse detection of precise tuning of the photodiode's operating parameters to coincide with a nonlinearity minimum. These results should also apply more generally to reduce nonlinear distortion in a range of other microwave photonics applications.

miR-16-1-3p targets TWIST1 to inhibit cell proliferation and invasion in NSCLC.

In our study, the impact of miR-16-1-3p on cell proliferation and invasion in NSCLC was explored. miR-16-1-3p mimics were transfected to A549 cells for miR-16-1-3p overexpression. qRT- PCR and Western blot were applied to explore the relative expression of mRNA and protein in A549 cells. Furthermore, the cell proliferation capability was determined by MTT assay. Additionally, cell migration and invasion were measured using a scratch assay and transwell assay, respectively. Moreover, TargetScan and luciferase reporter assay was utilized to investigate the target of miR-16-1-3p. The results indicated that miR-16-1-3p was downregulated in NSCLC cells and upregulation of miR-16-1-3p was able to inhibit the expression of TWIST1. In addition, the reduced cell proliferation, inhibited cell migration and invasion were observed in miR-16-1-3p mimic group compared to the negative control group. The luciferase reporter gene showed that TWIST1 was a target of miR-16-1-3p. Therefore, the present study demonstrated that miR-16-1-3p may suppress A549 cell proliferation, migration and invasion by targeting TWIST1. Thus, miR-16-1-3p might play important roles in NSCLC development, which provides a novel aspect for NSCLC investigation (Fig. 6, Ref. 26).

[Study of antioxidant effect of cannabinoid receptor type 2 agonist on rat hepatic stellate cell line].

Objective: To investigate the action and antioxidant effects of CB2 agonist AM-1241 on rat hepatic stellate cell line (HSC-T6). Methods: HSC-T6 was randomly divided into four groups: control group, oxidative stress group, AM-1241 intervention group and AM-1241+AM-630 antagonist group. Survival rate of HSC-T6 was detected by thiazolyl blue assay under 24 h interventions with 0, 20, 50, 80 µmol/L AM-1241 and 0, 10, 20, 30, 40 µmol/L AM-630, respectively. Besides control group, the remaining groups were well cultured in low-glucose DMEM containing 100 mU/L glucose oxidase (GO) for 12 h to prepare the oxidative stress model. Then, AM-1241 intervention group was treated with 50 µmol/L low-glucose DMEM medium. After incubation for 12 h, the AM-1241+AM-630 antagonist group was treated with CB2 antagonist AM-630 (20 µmol/L) for 2 h, and cultured with 50 µmol/L AM-1241 in complete low-glucose medium for 12 h. The optimal drug concentration was selected according to the cell viability considered by the experiment results. Type III collagen (C III) content in the HSC-T6 supernatant was detected by enzyme-linked immunosorbent assay. Glutathione (GSH) content in HSC-T6 was detected by spectrophotometry. CB2 and heme oxygenase-1(HO-1) in each group of HSC-T6 were detected by western blotting. Results: HSC-T6 proliferation was inhibited in each group of AM-1241 in a concentration-dependent manner (P < 0.05). The inhibition was highest at 80µmol/L, and the cell survival rate was (41.61% ± 3.13%) (P < 0.05). AM-630 concentration group had no significant inhibitory effect on the proliferation of HSC-T6 (P > 0.05). HSC-T6 expressed CB2 receptor in each group. The expression level of CB2 in the AM-1241 intervention group was higher compare with control group (P < 0.05).The expression of Col III were significantly higher in oxidative stress group (P < 0.05) than in control group, and the expression of Col III of AM-1241 intervention group was significantly lower than that in oxidative stress group (P < 0.05). Col III level in AM-1241+AM-630 antagonistic group was significantly higher than that in AM-1241 intervention group (P < 0.05). There was no significant difference between AM-1241+AM-630 antagonistic group and oxidative stress group (P > 0.05). The content of GSH and HO-1 in oxidative stress group was higher (P < 0.05) than control group. The content of GSH and HO-1 in the AM-1241 intervention group was higher compared with oxidative stress group, while content of AM-1241 + AM-630 antagonist group was lower compared to AM-1241 intervention group (P < 0.05), and the differences were not statistically significant for oxidative stress group. Conclusion: CB2 agonist AM-1241 can inhibit the proliferation and activation of HSC-T6 and its mechanism may activate the nuclear translocation of Nrf2 binding to HSC-T6, initiating the up-regulation of antioxidant enzymes HO-1 and GSH protein expression, and thus increase the antioxidant effect of HSC-T6.

Polarization mode control of long-wavelength VCSELs by intracavity patterning.

Polarization mode control is enhanced in wafer-fused vertical-cavity surface-emitting lasers emitting at 1310 nm wavelength by etching two symmetrically arranged arcs above the gain structure within the laser cavity. The intracavity patterning introduces birefringence and dichroism, which discriminates between the two polarization states of the fundamental transverse modes. We find that the cavity modifications define the polarization angle at threshold with respect to the crystal axes, and increase the gain anisotropy and birefringence on average, leading to an increase in the polarization switching current. Experimental measurements are explained using the spin-flip model of VCSEL polarization dynamics.

A rabbit model of antegrade selective cerebral perfusion with cardioplegic arrest.

OBJECTIVE: Due to the weak ascending aorta, it is extremely challenging to establish an anterograde selective cerebral perfusion (ASCP) model in rabbits, especially when cardioplegic arrest is required. Herein, the aim of this study was to establish a rabbit ASCP model with cardiac arrest being easily performed and being similar to the clinical scenario. MATERIALS AND METHODS: Twenty-two adult New Zealand white rabbits were selected for ASCP model establishment and another 22 rabbits were utilized for blood donation. The cardiopulmonary bypass (CPB) circuit consisted of a roller pump, a membrane oxygenator, a heat-cooler system and a blood reservoir, which were connected by silicone tubing. The total priming volume of the circuit was 70 ml. Cannulations on the right and left subclavian arteries were used for arterial inflow and cardioplegia perfusion, respectively. Venous drainage was conducted through the right atrial appendage. ASCP was initiated by clamping the innominate artery; the flow rate was maintained 10 ml/kg/minute and sustained for 60 minutes. After 120 minutes of reperfusion, the rabbits were sacrificed. The mean arterial pressure, heart rate, electrocardiogram and urine output were monitored. Arterial blood samples were analyzed at the following time points: after anesthesia, immediately after CPB, after aorta cross-clamping and cardioplegia perfusion, 5 min after the re-opening of the aorta and at CPB termination. RESULTS: ASCP modeling was performed successfully on 18 rabbits and 4 rabbits unsuccessfully. Vital signs and blood gas indictors changed in an acceptable range throughout the experiments. One rabbit had ventricular fibrillation after re-opening of the ascending aorta. Obvious hemodilution occurred after the perfusion of cardioplegia, but the hematocrit improved after CPB termination. CONCLUSION: By using cannulation of the subclavian artery rather than the aorta and with a low priming volume, we established a modified rabbit model of ASCP with cardioplegic arrest. The model has excellent repeatability and operability, which is similar to the clinic process and is suitable for the study of cerebral, cardiac and renal protection.

The split Renilla luciferase complementation assay is useful for identifying the interaction of Epstein-Barr virus protein kinase BGLF4 and a heat shock protein Hsp90.

Protein-protein interactions can regulate different cellular processes, such as transcription, translation, and oncogenic transformation. The split Renilla luciferase complementation assay (SRLCA) is one of the techniques that detect protein-protein interactions. The SRLCA is based on the complementation of the LN and LC non-functional halves of Renilla luciferase fused to possibly interacting proteins which after interaction form a functional enzyme and emit luminescence. The BGLF4 of Epstein-Barr virus (EBV) is a viral protein kinase that is expressed during the early and late stages of lytic cycles, which can regulate multiple cellular and viral substrates to optimize the DNA replication environment. The heat shock protein Hsp90 is a molecular chaperone that maintains the integrity of structure and function of various interacting proteins, which can form a complex with BGLF4 and stabilize its expression in cells. The interaction between BGLF4 and Hsp90 could be specifically detected through the SRLCA. The region of aa 250-295 of BGLF4 is essential for the BGLF4/Hsp90 interaction and the mutation of Phe-254, Leu-266, and Leu-267 can disrupt this interaction. These results suggest that the SRLCA can specifically detect the BGLF4/Hsp90 interaction and provide a reference to develop inhibitors that disrupt the BGLF4/Hsp90 interaction.

Living with Mental Illness: A Cognitive Behavioural Group Psycho-education Programme with Women in Secure Settings.

UNLABELLED: The provision of psycho-educational groups for people diagnosed with schizophrenia is an important part of successful treatment. The value of such interventions is less clearly established in secure settings with no reports on women. Gender differences in the manifestation of schizophrenia highlight the importance of a gender-specific intervention. A 'Living with Mental Illness' group programme for women in a secure psychiatric setting is described and evaluated. Those who completed group treatments (n = 20; 63%) showed improved knowledge of schizophrenia, decreased fear of schizophrenia, greater insight and increased optimism and perceived control of the illness. They also showed increased hope and greater self-compassion. Pre-post group findings reflected improved ratings of compliance with drug treatments, appropriate behaviour and insight into risk. This was reflected in a decrease in risk behaviours, improved attendance at treatment sessions and a reduction in symptomatology. Group members also reported a positive group therapeutic alliance. Findings are discussed in the context of gender-specific treatment, research, methodological issues characteristic of a real-world evaluations and the need to assess the long-term benefits of such treatment. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Psycho-educational groups for secure inpatients with schizophrenia need to address gender-specific differences in the manifestation of the condition. Such interventions as part of a broader treatment initiative can be associated with clinical improvement that is both illness specific and leads to improved engagement with care initiatives. The needs of patients who do not complete treatments needs to be regularly reassessed.