The Effect of a Reminiscence Therapy-Based Hybrid Board Game on Anxiety and Loneliness Levels in Older Adults: An Experimental Study.

Background: Anxiety and loneliness are prevalent psychological issues faced by older adults. To tackle these concerns, group reminiscence therapy has been widely recognized as an effective non-pharmacological form of intervention. Despite its proven efficacy, the implementation of this therapy normally requires professional guidance, limiting its accessibility to specialized institutions such as hospitals. Objective: In this study, the objective is to empirically validate the effectiveness of a reminiscence therapy-based hybrid board game, Journey of Memories, in reducing anxiety and loneliness among older adults. Method: We conducted a 12-day randomized controlled study. A total of 38 elderly participants aged between 61 and 75 were recruited. They were randomly assigned to an experimental group (consisting of 20 individuals) and a control group (consisting of 18 individuals). Participants in the experimental group were required to engage in three sessions of the Journey of Memories hybrid board game intervention, with a 5-day interval between each session. No intervention was administered to participants in the control group. Results: The results found that after 3 sessions of board game-based reminiscence therapy, 20 participants in the experimental group showed significant reductions in anxiety levels (the State Anxiety subscale of State-Trait Anxiety Inventory [STAI-S] average scores decreased from 43.83 to 41.05, P = 0.000, the Trait Anxiety subscale State-Trait Anxiety Inventory [STAI-T] average scores decreased from 46.72 to 43.61, P = 0.030) and loneliness levels (UCLA Loneliness Scale [UCLA] average scores decreased from 39.11 to 36.11, P = 0.002). In addition, participants reported high scores of usability (3.77/5) and user experience (4.08/5). Conclusion: These results demonstrate that the hybrid board game can effectively reduce older adults' feelings of anxiety and loneliness while providing a satisfactory user experience, motivating them to participate in group reminiscence therapy.

Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.

Structures and Energetics of E2H3+ (E = As, Sb, and Bi) Cations.

E2H2 (E = As, Sb, Bi) structures involving multiple bonds have attracted much attention recently. The E2H3+ cations (protonated E2H2) are predicted to be viable with substantial proton affinities (>180 kcal/mol). Herein, the bonding characters and energetics of a number of E2H3+ isomers are explored through CCSD(T) and DFT methods. For the As2H3+ system, the CCSD(T)/cc-pVQZ-PP method predicts that the vinylidene-like structure lies lowest in energy, with the trans and cis isomers higher by 6.7 and 9.3 kcal/mol, respectively. However, for Sb2H3+ and Bi2H3+ systems, the trans isomer is the global minimum, while the energies of the cis and vinylidene-like structures are higher, respectively, by 2.0 and 2.4 kcal/mol for Sb2H3+ and 1.6 and 15.0 kcal/mol for Bi2H3+. Thus, the vinyledene-like structure is the lowest energy for the arsenic system but only a transition state of the bismuth system. With permanent dipole moments, all minima may be observable in microwave experiments. Besides, we have also obtained transition states and planar-cis structures with higher energies. The current results should provide new insights into the various isomers and provide a number of predictions for future experiments.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

ALKBH5-mediated m6A demethylation fuels cutaneous wound re-epithelialization by enhancing PELI2 mRNA stability.

BACKGROUND: Impaired wound re-epithelialization contributes to cutaneous barrier reconstruction dysfunction. Recently, N6-methyladenosine (m6A) RNA modification has been shown to participate in the determination of RNA fate, and its aberration triggers the pathogenesis of numerous diseases. Howbeit, the function of m6A in wound re-epithelialization remains enigmatic. METHODS: Alkbh5‒/‒ mouse was constructed to study the rate of wound re-epithelialization after ALKBH5 ablation. Integrated high-throughput analysis combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq was used to identify the downstream target of ALKBH5. In vitro and in vivo rescue experiments were conducted to verify the role of the downstream target on the functional phenotype of ALKBH5-deficient cells or animals. Furthermore, the interacting reader protein and regulatory mechanisms were determined through RIP-qPCR, RNA pull-down, and RNA stability assays. RESULTS: ALKBH5 was specifically upregulated in the wound edge epidermis. Ablation of ALKBH5 suppressed keratinocyte migration and resulted in delayed wound re-epithelialization in Alkbh5‒/‒ mouse. Integrated high-throughput analysis revealed that PELI2, an E3 ubiquitin protein ligase, serves as the downstream target of ALKBH5. Concordantly, exogenous PELI2 supplementation partially rescued keratinocyte migration and accelerated re-epithelialization in ALKBH5-deficient cells, both in vitro and in vivo. In terms of its mechanism, ALKBH5 promoted PELI2 expression by removing the m6A modification from PELI2 mRNA and enhancing its stability in a YTHDF2-dependent manner. CONCLUSIONS: This study identifies ALKBH5 as an endogenous accelerator of wound re-epithelialization, thereby benefiting the development of a reprogrammed m6A targeted therapy for refractory wounds.

How we learn social norms: a three-stage model for social norm learning.

As social animals, humans are unique to make the world function well by developing, maintaining, and enforcing social norms. As a prerequisite among these norm-related processes, learning social norms can act as a basis that helps us quickly coordinate with others, which is beneficial to social inclusion when people enter into a new environment or experience certain sociocultural changes. Given the positive effects of learning social norms on social order and sociocultural adaptability in daily life, there is an urgent need to understand the underlying mechanisms of social norm learning. In this article, we review a set of works regarding social norms and highlight the specificity of social norm learning. We then propose an integrated model of social norm learning containing three stages, i.e., pre-learning, reinforcement learning, and internalization, map a potential brain network in processing social norm learning, and further discuss the potential influencing factors that modulate social norm learning. Finally, we outline a couple of future directions along this line, including theoretical (i.e., societal and individual differences in social norm learning), methodological (i.e., longitudinal research, experimental methods, neuroimaging studies), and practical issues.

Intraoperative Indocyanine Green Angiography Facilitates Flap Fenestration and Facial Organ Fabrication in Total Facial Restoration.

BACKGROUND: As effective measures to visualize flap vasculature and perfusion were unavailable, flap fenestration and facial organ fabrication could not be performed safely, preventing the transition from 2-D coverage to the restoration of the 3-D structure of facial organs. This study aims to evaluate the efficacy of indocyanine green angiography (ICGA) in guiding flap fenestration and facial organ fabrication in total facial restoration. METHODS: Ten patients with total facial scarring following burn injury were enrolled in the study. They were treated with pre-expanded, prefabricated monoblock flaps for total face restoration. The opening of nostrils, oral and palpebral orifices, together with organ fabrication, were conducted under the guidance of intraoperative ICGA via hemodynamic evaluation of flap perfusion. Postoperative follow-up parameters include vascular crisis, infection, flap necrosis and patients' aesthetic and functional recovery. RESULTS: The opening of facial organ orifices was performed at the stage of flap transfer in nine patients. To avoid damaging the major nourishing vessels, the left palpebral orifice was opened eight days after the flap transfer in one patient, as observed by ICGA. Based on ICGA evaluation, the decision to perform additional vascular anastomosis before flap fenestration was made in six patients. Hemodynamic analysis of flap perfusion following fenestration revealed no significant change. Follow-up showed satisfactory aesthetic recovery and well-restored 3-D structures of facial organs. CONCLUSION: This pilot study demonstrates how intraoperative ICGA can enhance the safety of flap fenestration, thereby transforming full facial restoration from the 2-D to the 3-D realm by facilitating facial organ fabrication.

The application of augmented reality in plastic surgery training and education: A narrative review.

Continuing problems with fewer training opportunities and a greater awareness of patient safety have led to a constant search for an alternative technique to bridge the existing theory-practice gap in plastic surgery training and education. The current COVID-19 epidemic has aggravated the situation, making it urgent to implement breakthrough technological initiatives currently underway to improve surgical education. The cutting edge of technological development, augmented reality (AR), has already been applied in numerous facets of plastic surgery training, and it is capable of realizing the aims of education and training in this field. In this article, we will take a look at some of the most important ways that AR is now being used in plastic surgery education and training, as well as offer an exciting glimpse into the potential future of this field thanks to technological advancements.

Lean adipose tissue macrophage derived exosome confers immunoregulation to improve wound healing in diabetes.

Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.

Effects of Organic Chromium Yeast on Performance, Meat Quality, and Serum Parameters of Grow-Finish Pigs.

Trivalent chromium (Cr) is an essential trace element for humans and animals. This study was conducted to investigate the effects of chromium(III) yeast (CrYst) on growth performance, carcass characteristics, meat traits, antioxidant status, immune traits, and serum biochemical parameters of grow-finish pigs. A total of 72 commercial hybrid barrows (Duroc × Landrace × Large White) of approximately 50 kg body weight were allocated into two dietary treatments randomly, which received a corn-soybean meal basal diet or a basal diet supplemented with 100 mg CrYst/kg. The trial duration was 11 weeks divided into three periods from body weights of 50-75 kg, 75-100 kg, and 100-110 kg, respectively. The results revealed that supplemental CrYst did not affect growth performance. Organic CrYst supplementation significantly decreased the backfat depth and increased the meat tenderness score and juiciness score values in pigs (P < 0.05), while other carcass traits and meat traits indexes were unaffected. CrYst addition significantly decreased serum malondialdehyde (MDA) content of pigs in the whole growth phase; significantly increased the serum levels of immunoglobulin G (IgG), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) in growing pigs; and also increased the serum IgG, IgM, and GSH concentrations in pigs during the finishing phase (P < 0.05). Additionally, diets supplemented with CrYst significantly decreased the serum high-density lipoprotein cholesterol (HDL-C) content in growing pigs and significantly increased the serum LDL-C level at the fattening period (P < 0.05), whereas no significant differences were observed for the other serum biochemical indexes compared to the control pigs. In conclusion, CrYst supplementation could reduce lipid peroxidation and backfat thickness and improve the meat tenderness and juiciness, immune traits, and antioxidant status of pigs.

CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 is an RNA-binding protein controlling plant immunity via an RNA processing complex.

Plant innate immunity is capable of combating diverse and ever evolving pathogens. The plasticity of innate immunity could be boosted by RNA processing. Arabidopsis thaliana CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 (CPR5), a key negative immune regulator, is a component of the nuclear pore complex. Here we further identified CPR5 as a component of RNA processing complexes. Through genetic screening, we found that RNA splicing activator NineTeen Complex and RNA polyadenylation factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR, coordinately function downstream of CPR5 to activate plant immunity. CPR5 and these two regulators form a complex that is localized in nuclear speckles, an RNA processing organelle. Intriguingly, we found that CPR5 is an RNA-binding protein belonging to the Transformer 2 (Tra2) subfamily of the serine/arginine-rich family. The RNA recognition motif of CPR5 protein binds the Tra2-targeted RNA sequence in vitro and is functionally replaceable by those of Tra2 subfamily proteins. In planta, it binds RNAs of CPR5-regulated alternatively spliced genes (ASGs) identified by RNA-seq. ARGONAUTE 1 (AGO1) is one of the ASGs and, consistent with this, the ago1 mutant suppresses the cpr5 phenotype. These findings reveal that CPR5 is an RNA-binding protein linking RNA processing with plant immunity.

CD39+ Fibroblasts Enhance Myofibroblast Activation by Promoting IL-11 Secretion in Hypertrophic Scars.

Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently shown to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. In this study, we observed an increased fraction of CD39+ Fbs in HTS after screening four Fb subtypes (CD26+, CD36+, FAP+, and CD39+). CD39+ Fbs, enriched in the upper dermis, were positively correlated with scar severity. The transcriptional analysis of CD39+ and CD39- Fbs sorted from HTS revealed that IL-11 was more highly expressed in CD39+ Fbs. We then showed that IL-11 was upregulated in HTSs and that its expression was induced by TGFß1 in vitro. TGFß1 also stimulated the expression of CD39 at the transcriptional and protein levels, mediating the maintenance of the CD39+ phenotype. Furthermore, IL-11 facilitated myofibroblast activation and extracellular matrix production in both CD39+ and CD39- Fbs. Interestingly, CD39+ Fbs secreted more IL-11 on TGFß1 treatment and were less responsive to IL-11 than CD39- Fbs. Notably, a CD39 inhibitor effectively reduced stretch-induced scar formation and attenuated bleomycin-induced skin fibrosis, suggesting an antiscarring approach by targeting CD39+ Fbs.

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars.

BACKGROUND: Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions. METHODS: Quantitative real­time PCR (qRT­PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein-protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions. RESULTS: MiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues. CONCLUSIONS: This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

Inhibition of CUB and sushi multiple domains 1 (CSMD1) expression by miRNA-190a-3p enhances hypertrophic scar-derived fibroblast migration in vitro.

BACKGROUND: Hypertrophic scar (HTS) is a fibroproliferative skin disorder characterized by excessive cell proliferation, migration, and extracellular matrix (ECM) deposition. The CUB and Sushi multiple domains 1 (CSMD1) has previously been identified as the key regulatory gene of hypertrophic scar by a large sample GWAS study. However, further research has not yet been conducted to verify this finding in other HTS patients and to determine the underlying mechanism. RESULTS: In this study, we verified that CSMD1 was downregulated in both HTS tissue and HTS-derived fibroblasts. The knockdown of CSMD1 resulted in enhanced migration and fibronectin1 (FN1) secretion in fibroblasts in vitro. In addition, the upstream and downstream regulatory mechanisms of CSMD1 were also investigated through microRNA (miRNA) databases screening and RNA-sequencing (RNA-seq) respectively. The screening of four common microRNA (miRNA) databases suggested that miR-190a-3p binds to the CSMD1 and may regulate its expression. We confirmed that miR-190a-3p directly targeted the CSMD1-3'-UTR using luciferase reporter assays. Furthermore, the overexpression of miR-190a-3p showed promotion of migratory activity and FN1 secretion in fibroblasts, resembling the effect of CSMD1 knockdown; whereas the knockdown of miR-190a-3p exerted the opposite effect. Finally, transcriptomic analysis showed activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway in the CSMD1 knockdown fibroblasts. CONCLUSIONS: This study has validated the conclusions of the previous GWAS study conducted in Chinese population. In vitro experiments have provided further evidence on the function of CSMD1 in the development of HTS, and have also revealed the underlying upstream and downstream regulating mechanisms. Additionally, the JAK/STAT signaling pathway identified using RNA-seq might provide a potential treatment approach, especially for HTS.

Exendin-4 induces a novel extended effect of ischemic tolerance via crosstalk with IGF-1R.

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4), a drug that has been used in the clinical treatment of type 2 diabetes mellitus, also confers a neuroprotective effect against stroke. Although GLP-1 analogs were reported to induce sustained insulin secretion and glucose tolerance improved after cessation of treatment, no study has revealed whether Ex-4 exerts sustained neuroprotection against stroke and the underlying mechanism after treatment cessation. In this study, mice were pretreated with Ex-4 for 7 days, and middle cerebral artery occlusion (MCAO) was performed on different days after cessation of Ex-4 treatment. Ex-4 ameliorated neurological dysfunction and reduced the infarct volume induced by MCAO. These protective effects lasted for 6 days after the cessation of Ex-4 treatment and were associated with sustained upregulation of PI3K, AKT, mTOR, and HIF-1α levels, as well as HIF-1α downstream genes. Knockdown of GLP-1R or HIF-1α in the brain by short hairpin RNA abolished Ex-4 treatment-mediated neuroprotection. In normal mice, Ex-4 treatment led to instant upregulation of p-PI3K, p-AKT, p-mTOR, and HIF-1α expression levels, which quickly returned to normal after cessation of Ex-4 treatment, while the expression levels of insulin growth factor-1 receptor (IGF-1R) remained high for 6 days after Ex-4 cessation. Additionally, Ex-4 did not directly induce IGF-1 production, which was only induced by MCAO. Ex-4 induces extended cerebral ischemic tolerance. This neuroprotective effect is associated with activation of GLP-1R and upregulation of IGF-1R in the brain, and the latter then activates the PI3K/AKT/mTOR/HIF-1 signaling pathway via binding to IGF-1 secreted from the ischemic brain.

Glucagon-like peptide-1 cleavage product GLP-1(9-36) reduces neuroinflammation from stroke via the activation of insulin-like growth factor 1 receptor in astrocytes.

Glucagon-like peptide-1 (GLP-1) is an endogenous gut hormone and a key regulator in maintaining glucose homeostasis by stimulating insulin secretion. Its natural cleavage product GLP-1 (9-36), which was formerly considered a "bio-inactive" metabolite mainly due to its low affinity for GLP-1 receptor, possesses unique properties such as cardiovascular protection. Little is known about the effects and mechanisms of GLP-1 (9-36) in cerebral ischemia and reperfusion injury. Here, we report that systemic application of GLP-1 (9-36) in adult mice facilitated functional recovery and reduced infarct volume, astrogliosis, and neuronal apoptosis following middle cerebral artery occlusion and reperfusion. Interestingly, these effects were still observed in GLP-1 receptor knockout (Glp-1rKO) mice but were partially reversed in insulin-like growth factor 1 (IGF-1) receptor knockdown (Igf-1rKD) mice. Primary astrocytes were cultured and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), and enzyme-linked immunosorbent assay indicated that GLP-1 (9-36) pretreatment reduces tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 levels. This effect was not diminished in Glp-1rKO astrocytes but was reversed in Igf-1rKO astrocytes, emphasizing that the anti-inflammatory effect of GLP-1 (9-36) in astrocytes is independent of GLP-1 receptor signaling and is instead mediated by IGF-1 receptor. Immunoprecipitation experiments showed that GLP-1 (9-36) directly interacts with IGF-1 receptor in astrocytes. Western blot data indicated that GLP-1 (9-36) activates IGF-1 receptor and downstream PI3K-AKT pathway in astrocytes upon OGD/R injury, which was abrogated by preincubation with IGF-1 receptor autophosphorylation inhibitor picropodophyllin. Thus, our findings suggest that GLP-1 (9-36) improved stroke outcome by reducing inflammation in astrocytes via interaction with IGF-1 receptor.

Metagenomic Study Suggests That the Gut Microbiota of the Giant Panda (Ailuropoda melanoleuca) May Not Be Specialized for Fiber Fermentation.

Bamboo-eating giant panda (Ailuropoda melanoleuca) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas.

A New Energy-Critical Plane Damage Parameter for Multiaxial Fatigue Life Prediction of Turbine Blades.

As one of fracture critical components of an aircraft engine, accurate life prediction of a turbine blade to disk attachment is significant for ensuring the engine structural integrity and reliability. Fatigue failure of a turbine blade is often caused under multiaxial cyclic loadings at high temperatures. In this paper, considering different failure types, a new energy-critical plane damage parameter is proposed for multiaxial fatigue life prediction, and no extra fitted material constants will be needed for practical applications. Moreover, three multiaxial models with maximum damage parameters on the critical plane are evaluated under tension-compression and tension-torsion loadings. Experimental data of GH4169 under proportional and non-proportional fatigue loadings and a case study of a turbine disk-blade contact system are introduced for model validation. Results show that model predictions by Wang-Brown (WB) and Fatemi-Socie (FS) models with maximum damage parameters are conservative and acceptable. For the turbine disk-blade contact system, both of the proposed damage parameters and Smith-Watson-Topper (SWT) model show reasonably acceptable correlations with its field number of flight cycles. However, life estimations of the turbine blade reveal that the definition of the maximum damage parameter is not reasonable for the WB model but effective for both the FS and SWT models.

Multiaxial Fatigue Damage Parameter and Life Prediction without Any Additional Material Constants.

Based on the critical plane approach, a simple and efficient multiaxial fatigue damage parameter with no additional material constants is proposed for life prediction under uniaxial/multiaxial proportional and/or non-proportional loadings for titanium alloy TC4 and nickel-based superalloy GH4169. Moreover, two modified Ince-Glinka fatigue damage parameters are put forward and evaluated under different load paths. Results show that the generalized strain amplitude model provides less accurate life predictions in the high cycle life regime and is better for life prediction in the low cycle life regime; however, the generalized strain energy model is relatively better for high cycle life prediction and is conservative for low cycle life prediction under multiaxial loadings. In addition, the Fatemi-Socie model is introduced for model comparison and its additional material parameter k is found to not be a constant and its usage is discussed. Finally, model comparison and prediction error analysis are used to illustrate the superiority of the proposed damage parameter in multiaxial fatigue life prediction of the two aviation alloys under various loadings.