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Lei Chang - Top 30 Publications

(+)-Borneol suppresses conditioned fear recall and anxiety-like behaviors in mice.

Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors. The present study was to investigate the effects of (+)-Borneol on both contextual and cued fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into ventral hippocampus only reduced 24 h cued fear responses. Moreover, microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed anxiety-like behaviors in the open field test, light/dark exploration and the elevated plus maze test. As selective GABAA receptor antagonist bicuculline reversed the effect of (+)-Borneol on contextual fear paradigm and the drug potentiated GABA-evoked currents in acute hippocampus slices, modulation of the GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety-related disorders.

miR-145 targets the SOX11 3'UTR to suppress endometrial cancer growth.

To explore the functions of SOX (Sex determining Region Y-related HMG-box) family genes in endometrial cancer (EC) and determine the influence of miR-145/SOX11 on EC cell functions. The relationship between miR-145 and SOX11 was confirmed using TargetScan, miRNA databases and dual-luciferase reporter gene assays. The expression of SOX11 mRNA in tissue specimens was examined using RT-qPCR, while SOX11 protein expression in tissues and cell lines were detected through immunohistochemistry (IHC) and western blotting. After transfection using Lipofectamine 2000, the proliferation, migration, invasion and apoptosis of ECC-1 and HEC-1-A cells were assessed through colony formation, transwell and flow cytometry assays. The correlation of SOX11 expression with the prognosis outcomes of patients was analyzed using Kaplan-Meier analysis and the log-rank test. SOX11 showed high expression in EC, which is negatively correlated with a poor prognostic outcome of EC patients. The expression of miR-145 was lower in EC tissues than in adjacent tissues. MiR-145 significantly reduced the expression of SOX11. In ECC-1 cells, miR-145 suppressed the propagation, migration, and invasion of cells and promoted cell apoptosis. MiR-145 also inhibited the proliferation, migration, and invasion of HEC-1-A cells and facilitated cell apoptosis by inhibiting SOX11. MiR-145 targeted site 3 (3615) of the SOX11 3'UTR to affect the expression of SOX11. MiR-145 and its target gene SOX11 could serve as diagnostic markers for EC. MiR-145 targets the SOX11 3'UTR to inhibit its expression and suppress the propagation and metastasis of EC cells.

Exploration of Recent Mobile Technologies Applied in Nursing Education.

The development of science and technology has fundamentally changed people's lives and the way that medical systems function. Increasingly, mobile technologies are being introduced and integrated into classroom teaching and clinical applications, resulting in healthcare providers introducing innovative applications into health education. These applications enhance the clinical, education, and research expertise of medical staffs and nurses, while improving quality of care and providing new experiences for patients. In order to understand the current situation and trends in nursing education, the present study adopted literature analysis to explore the influence and effect of mobile technologies that have been introduced into nursing education from the school and clinical environments. The results found that students hold positive attitudes toward introducing these technologies into their curricula. Although these technologies may increase the work efficiency of nurses in the workplace, questions remain user perceptions and professional expression. Therefore, securing patient agreement and healthcare system approval were major turning points in the introduction of mobile technologies into nursing education. In the future, adapting mobile technologies for use in teaching materials and courses may be further developed. Moreover, empirical studies may be used in future research in order to facilitate the increasingly successful integration of relevant technologies into nursing education.

Reward sensitivity, impulse control, and social cognition as mediators of the link between childhood family adversity and externalizing behavior in eight countries.

Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents' rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.

Longitudinal Associations Between Parenting and Youth Adjustment in Twelve Cultural Groups: Cultural Normativeness of Parenting as a Moderator.

To examine whether the cultural normativeness of parents' beliefs and behaviors moderates the links between those beliefs and behaviors and youths' adjustment, mothers, fathers, and children (N = 1,298 families) from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and the United States) were interviewed when children were, on average, 10 years old and again when children were 12 years old. Multilevel models examined 5 aspects of parenting (expectations regarding family obligations, monitoring, psychological control, behavioral control, warmth/affection) in relation to 5 aspects of youth adjustment (social competence, prosocial behavior, academic achievement, externalizing behavior, internalizing behavior). Interactions between family level and culture-level predictors were tested to examine whether cultural normativeness of parenting behaviors moderated the link between those behaviors and children's adjustment. More evidence was found for within- than between-culture differences in parenting predictors of youth adjustment. In 7 of the 8 instances in which cultural normativeness was found to moderate the link between parenting and youth adjustment, the link between a particular parenting behavior and youth adjustment was magnified in cultural contexts in which the parenting behavior was more normative. (PsycINFO Database Record

MiR-143 inhibits endometrial cancer cell proliferation and metastasis by targeting MAPK1.

Endometrial cancer (EC) is one of the most commonly diagnosed gynecologic malignancies in the world, with the morbidity rate of over 7%. The mechanism of the pathogenesis has not been specifically elucidated to date, which is imperative for EC treatment. The aim of our study was to investigate the target relationship between miR-143 and mitogen-activated protein kinase 1 (MAPK1) and explore the effect of miR-143 on the endometrial cancers (EC) cells through targeting MAPK1. We collected EC tissues and adjacent tissues, and transfected miR-143 mimics and MAPK1 siRNA into EC cells with lipofectamine. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to examine the expression of miR-143 and MAPK1 mRNA and the protein expression of MAPK1. Cell counting kit-8, wound healing assay, flow cytometry and transwell assay were applied to examining the alteration of the proliferation, migration, cell cycle and invasion ability of EC cells. We predicted the targeting gene of miR-143 through bioinformatics analysis. MiR-143 was found under-expressed in EC tissues and cells. Overexpression of miR-143 or knockdown of MAPK1 in human EC cell line HEC-1B inhibited the EC cell proliferation, migration and invasion and induced apoptosis. MAPK1 was verified to be a target gene of miR-143. MiR-143 overexpression could effectively inhibit mRNA and protein expression of MAPK1 in HEC-1B cells. Collectively, miR-143 might inhibit the proliferation, migration and invasion of EC cells, and promote the apoptosis of EC cells by suppressing MAPK1. These findings provided a view for new and potential therapeutic method for the clinical treatment of EC.

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein Tat-nNOS-N1-133 or systemic administration of a small molecule ZL006 from days 4 to 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound.

Age Patterns in Risk Taking Across the World.

Epidemiological data indicate that risk behaviors are among the leading causes of adolescent morbidity and mortality worldwide. Consistent with this, laboratory-based studies of age differences in risk behavior allude to a peak in adolescence, suggesting that adolescents demonstrate a heightened propensity, or inherent inclination, to take risks. Unlike epidemiological reports, studies of risk taking propensity have been limited to Western samples, leaving questions about the extent to which heightened risk taking propensity is an inherent or culturally constructed aspect of adolescence. In the present study, age patterns in risk-taking propensity (using two laboratory tasks: the Stoplight and the BART) and real-world risk taking (using self-reports of health and antisocial risk taking) were examined in a sample of 5227 individuals (50.7% female) ages 10-30 (M = 17.05 years, SD = 5.91) from 11 Western and non-Western countries (China, Colombia, Cyprus, India, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the US). Two hypotheses were tested: (1) risk taking follows an inverted-U pattern across age groups, peaking earlier on measures of risk taking propensity than on measures of real-world risk taking, and (2) age patterns in risk taking propensity are more consistent across countries than age patterns in real-world risk taking. Overall, risk taking followed the hypothesized inverted-U pattern across age groups, with health risk taking evincing the latest peak. Age patterns in risk taking propensity were more consistent across countries than age patterns in real-world risk taking. Results suggest that although the association between age and risk taking is sensitive to measurement and culture, around the world, risk taking is generally highest among late adolescents.

Infantile hemangioma: factors causing recurrence after propranolol treatment.

BackgroundPropranolol is the first-choice treatment for severe infantile hemangioma (IH). However, 10- 30% of lesions relapse after propranolol treatment. The mechanisms underlying IH recurrence after propranolol treatment have not been completely elucidated.MethodsThis study combined an examination of hemodynamic changes with research regarding hemangioma stem cells (hscs) with differentially expressed microRNAs (miRNAs) to identify the factors affecting IH recurrence after propranolol treatment. Hemodynamic changes were monitored in 21 recurrent cases using high-frequency color Doppler ultrasound, and hscs were treated with different concentrations of propranolol. The levels of differentially expressed miRNAs and the activity of related pathways were then compared between 18 recurrent and 20 non-recurrent IH cases.ResultsDuring treatment, lesion depth and vessel density decreased, and the lesion resistance index increased. Obvious lesions and vessel signals were observed in recurrent cases compared with non-recurrent cases. Propranolol effectively inhibited hscs proliferation. Twenty-two differentially expressed miRNAs were found in the recurrent group compared with the non-recurrent group.ConclusionRecurrence may be attributed to a combination of events. Serum biomarkers and drug treatments for IH recurrence must be studied further.Pediatric Research advance online publication, 11 October 2017; doi:10.1038/pr.2017.220.

Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison.

To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS).

Inhibiting Histone Deacetylase 2 (HDAC2) Promotes Functional Recovery From Stroke.

Stroke is a leading cause of long-term disability worldwide. However, current therapies that promote functional recovery from stroke are limited to physical rehabilitation. No pharmacological therapy is available. Thus, understanding the role of histone deacetylase 2 (HDAC2) in the pathophysiological process of stroke-induced functional loss may provide a novel strategy for stroke recovery.

MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.

Neuronal nitric oxide synthase (nNOS) 1, mainly responsible for NO release in central nervous system (CNS) 2, plays a significant role in multiple physiological functions. However, the function of nNOS+ interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) 3-derived nNOS+ interneurons in fear learning. To determine the origin of nNOS+ interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE) 4, caudal ganglionic eminences (CGE) 5 and preoptic area (POA) 6. The results showed that MGE contained the most abundant precursors of nNOS+ interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS+ interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS+ interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG) 7 of nNOS knock-out (nNOS-/-) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS-/- but not the wild-type mice, suggesting the importance of nNOS+ neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS-/- mice or wild-type mice into DG of the nNOS-/- mice and found that only MGE cells from wild-type mice but not the nNOS-/- mice rescued the deficit in acquisition of the nNOS-/- mice, further confirming the positive role of nNOS+ neurons in fear learning.

Targeting MicroRNAs in Prostate Cancer Radiotherapy.

Radiotherapy is one of the most important treatment options for localized early-stage or advanced-stage prostate cancer (CaP). Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy. There is great interest in investigating mechanisms of radioresistance and developing novel treatment strategies to overcome radioresistance. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level, participating in numerous physiological and pathological processes including cancer invasion, progression, metastasis and therapeutic resistance. Emerging evidence indicates that miRNAs play a critical role in the modulation of key cellular pathways that mediate response to radiation, influencing the radiosensitivity of the cancer cells through interplaying with other biological processes such as cell cycle checkpoints, apoptosis, autophagy, epithelial-mesenchymal transition and cancer stem cells. Here, we summarize several important miRNAs in CaP radiation response and then discuss the regulation of the major signalling pathways and biological processes by miRNAs in CaP radiotherapy. Finally, we emphasize on microRNAs as potential predictive biomarkers and/or therapeutic targets to improve CaP radiosensitivity.

Contaminant characteristics and environmental risk assessment of heavy metals in the paddy soils from lead (Pb)-zinc (Zn) mining areas in Guangdong Province, South China.

In November 2016, the total metal concentrations in nine representative locations in lead (Pb)-zinc (Zn) mining areas, located in Guangdong Province, South China, were determined experimentally by flame atomic absorption spectrometer. The results indicated that the paddy soils were heavily contaminated with Cd (20.25 mg kg-1), Pb (1093.03 mg kg-1), and Zn (867.0 mg kg-1), exceeding their corresponding soil quality standard values and background values. According to the results, the mean enrichment factor levels of the studied metals decreased in the following order: Cd > Zn > Pb > Cu > Ni > Mn > Cr. Among these metals, Cd, Pb, and Zn were predominantly influenced by widespread anthropogenic activities. The highest concentrations of the studied metal pollutants were distributed in the areas surrounding the mining activity district. Multivariate statistical analysis indicated that the major contributing sources of the studied metals were metal ore mining, smelting, and processing activities. However, the composition of soil background was another potential source. Moreover, the assessment results of environment risks showed that the potential ecological risks, in decreasing order, were Cd > Pb > Zn > Cu > Ni > Cr > Mn. Additionally, the non-carcinogenic risk represented the trend of HI Pb > HI Mn > HI Zn > HI Cu , and the carcinogenic risk ranked as CR Cr > CR Cd > CR Ni . Among the environmental risk substances, Cd and Pb were the main contributors that pose ecological harm and health hazards through their serious pollution. Consequently, greater attention should be paid to this situation.

Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval.

Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD).

Puberty Predicts Approach But Not Avoidance on the Iowa Gambling Task in a Multinational Sample.

According to the dual systems model of adolescent risk taking, sensation seeking and impulse control follow different developmental trajectories across adolescence and are governed by two different brain systems. The authors tested whether different underlying processes also drive age differences in reward approach and cost avoidance. Using a modified Iowa Gambling Task in a multinational, cross-sectional sample of 3,234 adolescents (ages 9-17; M = 12.87, SD = 2.36), pubertal maturation, but not age, predicted reward approach, mediated through higher sensation seeking. In contrast, age, but not pubertal maturation, predicted increased cost avoidance, mediated through greater impulse control. These findings add to evidence that adolescent behavior is best understood as the product of two interacting, but independently developing, brain systems.

Identification of Missing Proteins in the Phosphoproteome of Kidney Cancer.

Identifying missing proteins (MPs) has been one of the critical missions of the Chromosome-Centric Human Proteome Project (C-HPP). Since 2012, over 30 research teams from 17 countries have been trying to search adequate and accurate evidence of MPs through various biochemical strategies. MPs mainly fall into the following classes: (1) low-molecular-weight (LMW) proteins, (2) membrane proteins, (3) proteins that contained various post-translational modifications (PTMs), (4) nucleic acid-associated proteins, (5) low abundance, and (6) unexpressed genes. In this study, kidney cancer and adjacent tissues were used for phosphoproteomics research, and 8962 proteins were identified, including 6415 phosphoproteins, and 44 728 phosphosites, of which 10 266 were unreported previously. In total, 75 candidate detections were found, including 45 phoshoproteins. GO analysis for these 75 candidate detections revealed that these proteins mainly clustered as membrane proteins and took part in nephron and kidney development. After rigorous screening and manual check, 9 of them were verified with the synthesized peptides. Finally, only one missing protein was confirmed. All mass spectrometry data from this study have been deposited in the PRIDE with identifier PXD006482.

Multiplexed sgRNA Expression Allows Versatile Single Nonrepetitive DNA Labeling and Endogenous Gene Regulation.

The CRISPR/Cas9 system has made significant contributions to genome editing, gene regulation and chromatin studies in recent years. High-throughput and systematic investigations into the multiplexed biological systems require simultaneous expression and coordinated functioning of multiple sgRNAs. However, current cotransfection based sgRNA coexpression systems remain inefficient, and virus-based transfection approaches are relatively costly and labor intensive. Here we established a vector-independent method allowing multiple sgRNA expression cassettes to be assembled in series into a single plasmid. This synthetic biology-based strategy excels in its efficiency, controllability and scalability. Taking the flexibility advantage of this all-in-one sgRNA expressing system, we further explored its applications in single nonrepetitive genomic locus imaging as well as coordinated gene regulation in live cells. With its full potency, our method will facilitate the research in understanding genome structure, function and dynamics.

(+)-Borneol is neuroprotective against permanent cerebral ischemia in rats by suppressing production of proinflammatory cytokines.

Stroke is one of the leading causes of disability and death globally. It occurs when a major artery is occluded in the brain and leads to death of cells within the injured tissue. (+)-Borneol, a simple bicyclic monoterpene extracted from traditional Chinese medicine, is widely used in various types of diseases. However, no study has proved the effects of (+)-borneol on functional recovery from permanent ischemic stroke and the mechanism is still unknown. Here, we report that in the rat model of permanent cerebral ischemia, we found that (+)-borneol (1.0 mg/kg) significantly ameliorated infarct size and neurological scoresvia reducing the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in a dose dependent manner. Notably, (+)-borneol showed long-term effects on the improvement of sensorimotor functions in the photothrombotic model of stroke, which decreased the number of foot faults in the grid-walking task and forelimb asymmetry scores in the cylinder task, at least in part through reducing loss of dendritic spines in the length, brunch number and density. These findings suggest that (+)-borneol could serve as a therapeutic target for ischemic stroke.

Severity and Justness Do Not Moderate the Relation Between Corporal Punishment and Negative Child Outcomes: A Multicultural and Longitudinal Study.

There is strong evidence of a positive association between corporal punishment and negative child outcomes, but previous studies have suggested that the manner in which parents implement corporal punishment moderates the effects of its use. This study investigated whether severity and justness in the use of corporal punishment moderate the associations between frequency of corporal punishment and child externalizing and internalizing behaviors. This question was examined using a multicultural sample from eight countries and two waves of data collected one year apart. Interviews were conducted with 998 children aged 7-10 years, and their mothers and fathers, from China, Colombia, Italy, Jordan, Kenya, Philippines, Thailand, and the United States. Mothers and fathers responded to questions on the frequency, severity, and justness of their use of corporal punishment; they also reported on the externalizing and internalizing behavior of their child. Children reported on their aggression. Multigroup path models revealed that across cultural groups, and as reported by mothers and fathers, there is a positive relation between the frequency of corporal punishment and externalizing child behaviors. Mother-reported severity and father-reported justness were associated with child-reported aggression. Neither severity nor justness moderated the relation between frequency of corporal punishment and child problem behavior. The null result suggests that more use of corporal punishment is harmful to children regardless of how it is implemented, but requires further substantiation as the study is unable to definitively conclude that there is no true interaction effect.

Intralesional Lidocaine Anesthesia: A Novel Facilitated Anesthesia Technique for Ethanol Sclerotherapy of Venous Malformation.

The aim of this study was to describe a novel anesthesia, intralesional lidocaine anesthesia (ILA), for ethanol sclerotherapy of venous malformation and evaluate the efficacy and safety.

Stepwise, Multi-Incisional, and Single-Stage Approach to Reshape Facial Contour After Large Cutaneous Lesion Resection.

Removal of large facial benign cutaneous lesions remains challenging. Serial or complete excisions together with local flaps or expander-based reconstructions are required. However, those techniques are time-consuming and may contribute to poor cosmetic and functional outcomes.

Development of bimolecular fluorescence complementation using rsEGFP2 for detection and super-resolution imaging of protein-protein interactions in live cells.

Direct visualization of protein-protein interactions (PPIs) at high spatial and temporal resolution in live cells is crucial for understanding the intricate and dynamic behaviors of signaling protein complexes. Recently, bimolecular fluorescence complementation (BiFC) assays have been combined with super-resolution imaging techniques including PALM and SOFI to visualize PPIs at the nanometer spatial resolution. RESOLFT nanoscopy has been proven as a powerful live-cell super-resolution imaging technique. With regard to the detection and visualization of PPIs in live cells with high temporal and spatial resolution, here we developed a BiFC assay using split rsEGFP2, a highly photostable and reversibly photoswitchable fluorescent protein previously developed for RESOLFT nanoscopy. Combined with parallelized RESOLFT microscopy, we demonstrated the high spatiotemporal resolving capability of a rsEGFP2-based BiFC assay by detecting and visualizing specifically the heterodimerization interactions between Bcl-xL and Bak as well as the dynamics of the complex on mitochondria membrane in live cells.

Within- and between-person and group variance in behavior and beliefs in cross-cultural longitudinal data.

This study grapples with what it means to be part of a cultural group, from a statistical modeling perspective. The method we present compares within- and between-cultural group variability, in behaviors in families. We demonstrate the method using a cross-cultural study of adolescent development and parenting, involving three biennial waves of longitudinal data from 1296 eight-year-olds and their parents (multiple cultures in nine countries). Family members completed surveys about parental negativity and positivity, child academic and social-emotional adjustment, and attitudes about parenting and adolescent behavior. Variance estimates were computed at the cultural group, person, and within-person level using multilevel models. Of the longitudinally consistent variance, most was within and not between cultural groups-although there was a wide range of between-group differences. This approach to quantifying cultural group variability may prove valuable when applied to quantitative studies of acculturation.

IL-36α suppresses proliferation of ovarian cancer cells.

Interleukin-36α (IL-36α), also formerly known as IL-1F6, is pertaining to IL-1 family members that has been shown to play an important pro-inflammatory role in chronic immune disorders. However, the role IL-36α in the setting of cancer remains unknown. Here, in our study, to investigate the clinical relevance of IL-36α in ovarian cancer, clinicopathological significance as well as expression level of IL-36α were analyzed in epithelial ovarian cancer clinical tissues and paired normal control. To explore the biological role of IL-36α in vitro in epithelial ovarian cancer cells, both overexpression and knockdown of IL-36α were performed. Based on the successful re-expression and silencing of IL-36α, proliferation, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound-healing, and Transwell assays, respectively. To further confirm the effect over proliferation in vivo, nude mice xenografted with epithelial ovarian cancer cells whose endogenous IL-36α was stably upregulated or downregulated were employed. It was found that IL-36α was shown to be markedly downregulated in epithelial ovarian cancer tissues relative to paired normal control and that reduced IL-36α expression was significantly associated with poor overall prognosis. In addition, IL-36α was observed to be able to suppress the growth of epithelial ovarian cancer cells both in vivo and in vitro. Taken together, IL-36α was displayed to be able to suppress the growth of epithelial ovarian cancer cells in our setting, which is suggestive of its druggable potential in curing the epithelial ovarian cancer and that upregulation of IL-36α was found to be capable of inhibiting the growth of epithelial ovarian cancer cells.

Effect of Working Memory Updating Training on Retrieving Symptoms of Children With Learning Disabilities.

Working memory (WM) deficiency is a primary reason for the poor academic performance of children with learning disabilities (LDs). Studies have shown that the WM of typical children could be improved through training, and WM training contributes to improving their fluid intelligence and academic achievement. However, few studies have investigated WM training for children with LDs, and results have been inconsistent. The present study examined the long-term effects of WM updating training and whether it can mitigate LD symptoms. Fifty-four children with LDs were recruited and divided randomly into a training or control group. The training group underwent adaptive running WM training for 20 days. Before and after training, the 2 groups completed a 2-back task, a digit span task (forward and backward), Raven's Standard Progressive Matrices test, and a scholastic attainment test (Chinese and math). The tests were repeated 6 months later. The results showed that, as compared with the controls, the training group exhibited significant improvements in the digit backward span task, 2-back task, and Raven's Standard Progressive Matrices. The math scores of the training group improved significantly by 6 months after the training. The results of this study suggest that WM updating training could mitigate the cognitive deficits of LDs and improve the WM capacity, fluid intelligence, and math scores of children with LDs. Moreover, the training effects could be maintained for at least 6 months.

Opening a New Time Window for Treatment of Stroke by Targeting HDAC2.

Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced histone deacetylase 2 (HDAC2) upregulation from 5 to 7 d after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knock-out of Hdac2 promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas overexpressing HDAC2 worsened stroke-induced functional impairment of both WT and Hdac2 conditional knock-out mice. More importantly, inhibiting other isoforms of HDACs had no effect. Thus, the intervention by precisely targeting HDAC2 in this window phase is a novel strategy for the functional recovery of stroke survivors.SIGNIFICANCE STATEMENT Narrow time window phase impedes current therapies for stroke patients. Understanding the key mechanisms underlying secondary injury may open a new window for pharmacological interventions to promote recovery from stroke. Our study indicates that ischemia-induced histone deacetylase 2 upregulation from 5 to 7 d after stroke mediates the secondary functional loss by reducing survival and neuroplasticity of peri-infarct neurons as well as augmenting neuroinflammation. Thus, precisely targeting histone deacetylase 2 in the window phase provides a novel therapeutic strategy for stroke recovery.

Clinical significance of C/D box small nucleolar RNA U76 as an oncogene and a prognostic biomarker in hepatocellular carcinoma.

Recent evidence has suggested novel roles of small nucleolar RNAs (snoRNAs) in tumorigenicity. However, the roles of C/D box snoRNA U76 (SNORD76) in the development of hepatocellular carcinoma (HCC) remain unknown. Herein, we systematically evaluated dysregulation of snoRNAs in HCC and clarified the biomarker potential and biological significance of SNORD76 in HCC.

ZL006 promotes migration and differentiation of transplanted neural stem cells in male rats after stroke.

New strategies must be developed to resolve the problems of stroke treatment. In recent years, stem cell-based therapy after stroke has come into the public and academic lens. Previously we have shown that uncoupling neuronal nitric oxide synthase (nNOS) from the postsynaptic density protein-95 (PSD-95) by ZL006, a small molecular compound, can ameliorate ischemic damage and promote neuronal differentiation of endogenous neural stem cells (NSCs) in focal cerebral ischemic male rats. In this study, we transplanted exogenous NSCs into the ipsilateral hemisphere of male rats in combination with ZL006 treatment after ischemic stroke. We show that ZL006 treatment facilitates the migration of transplanted NSCs into the ischemia-injured area and promotes neuronal differentiation of these cells, which is not due to a direct effect of ZL006 on exogenous NSCs but is associated with increased phosphorylation of cAMP response element-binding protein (CREB) in neurons and favorable microenvironment. Moreover, improved functional outcome in the ZL006-treated group was also found. Taken together, our data indicate that ZL006, uncoupling nNOS-PSD-95 in neurons, positively regulates the fate of transplanted NSCs and benefits the functional outcome after stroke in male rats.

Comparison of the efficacy among multiple chemotherapeutic interventions combined with radiation therapy for patients with cervix cancer after surgery: A network meta-analysis.

Cervix cancer was the second most common cancer in female. However, there was no network meta-analysis (NMA) comparing the efficacy of the multiple chemotherapeutic interventions combined with radiation therapy in patients after operation.