Research progress on ecological adaptation and prevention of Parengyodontium album on the surface of cultural relics.

Cultural relics as the crystallization of human history are non-renewable and irreplaceable resources. Microorganisms are widely colonized on ancient wall paintings, stone cultural relics, and other types of cultural heritages to cause harm. The dominant disease fungus, Parengyodontium album, is extensively distributed and can seriously threaten the long-term preservation of precious cultural heritage due to surviving in various cultural relics and extreme environments. The classification and nomenclature of P. album have undergone several changes, so its impact on cultural relic received little attention. Here, we summarized the brief histories of its classification and development, distribution range, and cultural heritage preference of P. album. We further analyzed the physiological, biochemical, and ecological characteristics and potential biological degradation mechanism. We proposed that P. album could be used as an indicative species of microbial hazardous effects on cultural heritage. We discussed the prevention and control countermeasures of such typical mural microorganisms and pointed out key research directions in this field.

Systemic inflammation response index predicts the postoperative recurrence of chronic rhinosinusitis with nasal polyps: a retrospective study in the Chinese population.

PURPOSE: Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. METHODS: A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. RESULTS: Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. CONCLUSION: SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.

Patient Needs in Psoriasis Treatment and their Influencing Factors: A Nationwide Multicentre Cross-Sectional Study in China.

Background: The management and treatment of psoriasis has rarely considered patient needs, which are numerous, multi-dimensional and are of great importance to improving treatment outcomes. Objectives: This study aimed to evaluate and compare the patients' needs for psoriasis treatment and identify factors predicting the need to make patient-centred decisions about treatment. Materials and Methods: This nationwide multicentre cross-sectional study included subjects between October 2020 and August 2021. The status quo of the needs in psoriasis treatment and their influencing factors were analysed mainly using the Chi-square test and binary logistic regression. Results: Information on sociodemographic and clinical characteristics were obtained. Factor analysis of a specially designed questionnaire showed that rapid skin clearance, reduced treatment expense and fewer hospital visits or treatment time were the first three patient needs in psoriasis treatment. Several influencing factors were important including the sociodemographic characteristics of gender, marital status, education level and family history, special location of skin lesions, dermatology life quality index (DLQI), Investigator's Global Assessment modified 2011 (IGA mod 2011), condition of the episode, clinical type of psoriasis, seasonal exacerbation and therapy. Conclusions: Patients with psoriasis pursued a wide range of treatment goals, with the most desired being rapid skin clearance, reduced treatment expense and time-saving. Paying attention to sex, marital status, education level, the special location of skin lesions and the DLQI will help dermatologists develop patient-centred treatment, meet the patient's needs and eventually improve the treatment outcomes.

Differences of airborne and mural microorganisms in a 1,500-year-old Xu Xianxiu's Tomb, Taiyuan, China.

Background: Microbial colonization represents one of the main threats to the conservation of subterranean cultural heritage sites. Recently, the microbial colonization on murals in tombs has gradually attracted attention. Methods: In this study, a total of 33 samples, including 27 aerosol samples and 6 mural painting samples, were collected from different sites of Xu Xianxiu's Tomb and analyzed using culture-dependent methods. We compared the diversities of culturable bacteria and fungi isolated from the air and murals and explored the potential impacts of microorganisms on the biodeterioration of the murals. Results: Phylogenetic analyses revealed that the culturable bacteria belonged to Bacillus, Microbacterium, Lysobacter and Arthrobacter. And the most of fungal belonged to the Penicillium, Cladosporium and Aspergillus genera. The composition and structure of airborne bacteria and fungi outside the tomb were both significantly different from that inside the tomb. The variation trends of airborne bacterial and fungal concentrations at different sampling sites were remarkably similar. Bacillus frigoritolerans, Bacillus halotolerans, Bacillus safensis, Exiguobacterium mexicanum, Microbacterium trichothecenolyticum, and Micrococcus yunnanensis were bacterial species commonly isolated from both the mural and air environments. Fungal species commonly isolated from aerosol samples and mural painting samples were Alternaria alternata, Cladosporium cladosporioides, Penicillium brevicompactum, and Peyronellaea glomerata. The prediction of the ecological functions of the bacteria revealed that chemoheterotrophy or aerobic_chemoheterotrophy accounted for substantial relative proportions in all sample types. Conclusion: These results suggest that the aerosol circulation between the inside and outside environments of the tomb was weak and that the outside environment had yet to have an impact on the air microbial community inside the tomb. Selective colonization of microorganisms, which is mediated by interaction between microorganisms and special microenvironmental factors, is an important reason for the biodeterioration of murals.

Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, although newly developing targeted therapy and immunotherapy have been showing promising effects in clinical treatment, the effective biomarkers for immune response prediction are still lacking. The study is to construct a gene signature according to ccRCC immune cells infiltration landscape, thus aiding clinical prediction of patients response to immunotherapy. METHODS: Firstly, ccRCC transcriptome expression profiles from Gene Expression Omnibus (GEO) database as well as immune related genes information from IMMPORT database were combine applied to identify the differently expressed meanwhile immune related candidate genes in ccRCC comparing to normal control samples. Then, based on protein-protein interaction network (PPI) and following module analysis of the candidate genes, a hub gene cluster was further identified for survival analysis. Further, LASSO analysis was applied to construct a signature which was in succession assessed with Kaplan-Meier survival, Cox regression and ROC curve analysis. Moreover, ccRCC patients were divided as high and low-risk groups based on the gene signature followed by the difference estimation of immune treatment response and exploration of related immune cells infiltration by TIDE and Cibersort analysis respectively among the two groups of patients. RESULTS: Based on GEO and IMMPORT databases, a total of 269 differently expressed meanwhile immune related genes in ccRCC were identified, further PPI network and module analysis of the 269 genes highlighted a 46 genes cluster. Next step, Kaplan-Meier and Cox regression analysis of the 46 genes identified 4 genes that were supported to be independent prognosis indicators, and a gene signature was constructed based on the 4 genes. Furthermore, after assessing its prognosis indicating ability by both Kaplan-Meier and Cox regression analysis, immune relation of the signature was evaluated including its association with environment immune score, Immune checkpoint inhibitors expression as well as immune cells infiltration. Together, immune predicting ability of the signature was preliminary explored. CONCLUSIONS: Based on ccRCC genes expression profiles and multiple bioinformatic analysis, a 4 genes containing signature was constructed and the immune regulation of the signature was preliminary explored. Although more detailed experiments and clinical trials are needed before potential clinical use of the signature, the results shall provide meaningful insight into further ccRCC immune researches.

Nacre-mimetic Strategy to Fabricate Waterborne FrGO/Zn/Epoxy Coatings with Dual Corrosion Protection.

The service life of metal and other infrastructure requires extending through eco-friendly, low-carbon technology. Here, a nacre-mimetic γ-Fe2O3/reduced graphene oxide (FrGO)/zinc-containing epoxy coating (FrGO/Zn/epoxy coating) was fabricated by spraying a mixture of waterborne epoxy resin, zinc flakes, and magnetic conductive FrGO under a magnetic field. The FrGO, which was synthesized by in situ redox and precipitation, was aligned in the zinc-containing coatings (ZCC), and it oriented the zinc flakes in the direction of the magnetic field to mimic the lamellar structure of nacre. The obtained anti-corrosion coating showed enhanced barrier protection and cathodic protection, which was confirmed by the electrochemical tests and salt spray test results. The waterborne coatings less than 50 µm thick with parallelly aligned FrGO and 30 wt % zinc flakes exhibited a long cathodic period lasting more than 99 days and excellent barrier performance with a high initial coating resistance of 5.31 × 109 Ω·cm2, which was superior to that of the conventional zinc-rich coating containing 80 wt % zinc (80 days, 3.74 × 103 Ω·cm2). The dual anti-corrosion mechanism of the waterborne FrGO/Zn/epoxy coating was investigated. The integrity and long-term cathodic protection of the coatings were derived from the compactness achieved by the nacre-mimetic structure and the interface chemical and hydrogen bonding crosslinking interactions and the high, uniform zinc utilization achieved by the aligned FrGO-Zn charge transmission network. This work provides a feasible nacre-inspired strategy to fabricate a lightweight anti-corrosion waterborne ZCC that is resource-efficient and promising in creating compact materials with other functional properties, such as electromagnetic shielding and conductive networks.

Interrelationships between sarcopenia, bone turnover markers and low bone mineral density in patients on hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are at risk for sarcopenia (SP) and bone loss, which may impact falls and bone fragility and lead to poor prognosis. Patients with HD and those with osteoporosis (OP) are still underdiagnosed and untreated. The aims of the present study were to evaluate the factors that affect bone mineral density (BMD) loss in HD patients, and explore traditional and novel approaches to manage chronic kidney disease-mineral-bone disorder (CKD-MBD). METHODS: Patients who underwent regular HD at the First Affiliated Hospital of Soochow University were retrospectively evaluated. According to the WHO osteoporosis criteria, patients were categorized into three groups: normal BMD, osteopenia, and osteoporosis. Demographic and clinical data, skeletal muscle mass, and bone turnover markers(BTM) were compared between the three groups. The correlation between bone density and muscle mass was calculated, and related risk factors were analyzed. RESULTS: This study enrolled 130 HD patients, 36 patients were diagnosed with sarcopenia (27.7%), 44 patients were diagnosed with osteopenia (33.8%), 19 patients were diagnosed with osteoporosis (14.6%), and 23 patients were diagnosed with osteosarcopenia (17.7%). The SMI was positively correlated with the BMD of the lumbar spine (r = 0.23, p < 0.01) and femoral neck (r = 0.22, p < 0.05). In ordinal logistic regression analysis, the odds ratio (OR) for low BMD was high for patients with sarcopenia (OR = 5.894, 95% CI 1.592-21.830, p < 0.01), older age (OR = 1.095, 95% CI 1.041-1.153, p < 0.001), higher TRACP-5b levels (OR = 1.597, 95% CI 1.230-2.072, p < 0.01), and lower 25-OH vitamin D levels (OR = 0.631, 95% CI 0.544-0.733, p < 0.001). CONCLUSION: The preservation of skeletal muscle mass could be important to prevent a BMD decrease in HD patients. Adequate intake of vitamin D and control of TRACP-5b levels will help reduce the occurrence and progression of osteopenia/sarcopenia in HD patients.

Osteosarcoma transcriptome data exploration reveals STC2 as a novel risk indicator in disease progression.

BACKGROUND: Osteosarcoma has been the most common primary bone malignant tumor in children and adolescents. Despite the considerable improvement in the understanding of genetic events attributing to the rapid development of molecular pathology, the current information is still lacking, partly due to the comprehensive and highly heterogeneous nature of osteosarcoma. The study is to identify more potential responsible genes during the development of osteosarcoma, thus identifying promising gene indicators and aiding more precise interpretation of the disease. METHODS: Firstly, from GEO database, osteosarcoma transcriptome microarrays were used to screen the differential expression genes (DEGS) in cancer comparing to normal bone samples, followed by GO/KEGG interpretation, risk score assessment and survival analysis of the genes, for the purpose of selecting a credible key gene. Further, the basic physicochemical properties, predicted cellular location, gene expression in human cancers, the association with clinical pathological features and potential signaling pathways involved in the key gene's regulation on osteosarcoma development were in succession explored. RESULTS: Based on the selected GEO osteosarcoma expression profiles, we identified the differential expression genes in osteosarcoma versus normal bone samples, and the genes were classified into four groups based on the difference level, further genes interpretation indicated that the high differently level (> 8 fold) genes were mainly located extracellular and related to matrix structural constituent regulation. Meanwhile, module function analysis of the 67 high differential level (> 8 fold) DEGS revealed a 22-gene containing extracellular matrix regulation associated hub gene cluster. Further survival analysis of the 22 genes revealed that STC2 was an independent prognosis indicator in osteosarcoma. Moreover, after validating the differential expression of STC2 in cancer vs. normal tissues using local hospital osteosarcoma samples by IHC and qRT-PCR experiment, the gene's physicochemical property revealed STC2 as a cellular stable and hydrophilic protein, and the gene's association with osteosarcoma clinical pathological parameters, expression in pan-cancers and the probable biological functions and signaling pathways it involved were explored. CONCLUSION: Using multiple bioinformatic analysis and local hospital samples validation, we revealed the gain of expression of STC2 in osteosarcoma, which associated statistical significantly with patients survival, and the gene's clinical features and potential biological functions were also explored. Although the results shall provide inspiring insights into further understanding of the disease, further experiments and detailed rigorous clinical trials are needed to reveal its potential drug-target role in clinical medical use.

Trait anxiety is related to an impaired attention model for controllable threat cues: Evidence from ERPs.

Attentional bias to threat cues is maladaptive for individuals with high trait anxiety (HTA), but may become adaptive when the dangers signaled by these cues can be controlled by timely actions. However, it remains unclear how HTA individuals allocate attention to controllable threat cues. The current study examined whether trait anxiety is associated with an impaired attention model for controllable threat cues and explored the related underlying neural mechanisms. A sample of 21 participants with low trait anxiety (LTA) and 21 with HTA completed a modified cued anticipation task which allowed participants to control the appearance of threatening pictures associated with controllable threat cues. Results revealed that HTA individuals had no difference in N1 amplitude among controllable threat cues, uncontrollable threat cues, and neutral cues, while LTA individuals showed the greatest N1 amplitude on controllable cues. HTA individuals also exhibited lower N2 amplitude than LTA individuals. The current study provides electrophysiological evidence showing that HTA individuals have impaired attention for processing controllable threat cues and weak inhibitory control. Deficient attention to controllable threat cues may be crucial in the mechanisms underlying trait anxiety.

Phase-Changing Polymer Film for Smart Windows with Highly Adaptive Solar Modulation.

Adjusting sunlight and thermal radiation from windows is important in efficient energy-saving applications. A high solar modulation (ΔTsol) capability as well as a high luminous transmittance (Tlum) are the ultimate aim of smart windows. In this study, hydroxypropyl cellulose (HPC), W-doped VO2, and poly-N-iso-propylacrylamide (PNIPAm) composite hydrogel films were produced. The sample was prepared between two glasses to constitute a smart window with a sandwich construction structure, which exhibits a high Tlum of 87.16%, a ΔTsol of 65.71%, and a lower critical solution temperature (LCST) of 29 °C. The practical applications of conventional PNIPAm hydrogels are limited by the volume contraction of phase transition. Here, this challenge is addressed by the simple method of combining with HPC. The PNIPAm-2.5 wt % HPC hydrogels possess thermo-responsive contractility with a volume shrinkage rate of 8.5%. Even after 100 high- and low-temperature cyclic durability tests, the smart windows still exhibit a high solar modulation capability.

Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity.

Hepatic glucose production (HGP) is an important component of glucose homeostasis, and deregulated HGP, particularly through gluconeogenesis, contributes to hyperglycemia and pathology of type-2 diabetes (T2D). It has been shown that the gluconeogenic gene expression is governed primarily by the transcription factor cAMP-response element (CRE)-binding protein (CREB) and its coactivator, CREB-regulated transcriptional coactivator 2 (CRTC2). Recently, we have discovered that Sam68, an adaptor protein and Src kinase substrate, potently promotes hepatic gluconeogenesis by promoting CRTC2 stability; however, the detailed mechanisms remain unclear. Here we show that in response to glucagon, Sam68 increases CREB/CRTC2 transactivity by interacting with CRTC2 in the CREB/CRTC2 complex and occupying the CRE motif of promoters, leading to gluconeogenic gene expression and glucose production. In hepatocytes, glucagon promotes Sam68 nuclear import, whereas insulin elicits its nuclear export. Furthermore, ablation of Sam68 in hepatocytes protects mice from high-fat diet (HFD)-induced hyperglycemia and significantly increased hepatic and peripheral insulin sensitivities. Thus, hepatic Sam68 potentiates CREB/CRTC2-mediated glucose production, contributes to the pathogenesis of insulin resistance, and may serve as a therapeutic target for T2D.

Molecular profiling of gene fusions in soft tissue sarcomas by Ion AmpliSeqTM: a study of 35 cases.

Background: The accurate diagnosis of sarcoma can be difficult as there are over 70 different subtypes. While molecular profiling in soft tissue sarcoma (STS) has gradually been incorporated into routine diagnostics, conventional methods such as fluorescence in situ hybridization (FISH), reverse transcriptase-PCR (RT-PCR), and Sanger sequencing have several drawbacks. By allowing simultaneous analysis of multiple targets and increasing sequencing depth to achieve ultra-sensitivity, next-generation sequencing (NGS) can not only detect common genetic abnormalities without prior assumptions but also identify uncommon or even new variants. Methods: In this study, the applicability of NGS in assessing STS using the Ion Torrent Proton was evaluated and compared with other methods. A cohort of 35 tissue specimens from STS patients, including alveolar soft-part sarcoma (ASPS), Ewing's sarcoma (ES), synovial sarcoma (SS), dermatofibrosarcoma protuberans (DFSP), and myxoid liposarcoma (MLPS) patients, were subjected to NGS by an Ion AmpliSeqTM Custom panel. Results: A proportion of 97.14% (34/35) were successfully conducted to detect gene fusion positive events and met all criteria for good quality. The concordance between NGS and conventional techniques was 94.12% (32/34). NGS also showed superior results, as Sanger sequencing and FISH in two cases were false negatives, demonstrating the excellent diagnostic utility of NGS for translocation detection in STS. Conclusions: The results in this study show the potential for NGS to aid in diagnosis and clinical monitoring of STS and warrant additional studies in larger cohorts.

Palladium-catalyzed hydroboration reaction of unactivated alkynes with bis (pinacolato) diboron in water.

A highly efficient and mild palladium-catalyzed hydroboration of unactivated internal alkynes in water is described. Both aryl- and alkyl-substituted alkynes proceeded smoothly within the reaction time to afford the desired vinylboronates in moderate to high yields. Bis (pinacolato) diboron was used to afford α- and ß-hydroborated products in the presence of HOAc. These reactions showed high reactivities and tolerance, thus providing a promising method for the synthesis of alkenyl boron compounds.

Application of New Energy Thermochromic Composite Thermosensitive Materials of Smart Windows in Recent Years.

Thermochromic smart windows technology can intelligently regulate indoor solar radiation by changing indoor light transmittance in response to thermal stimulation, thus reducing energy consumption of the building. In recent years, with the development of new energy-saving materials and the combination with practical technology, energy-saving smart windows technology has received more and more attention from scientific research. Based on the summary of thermochromic smart windows by Yi Long research groups, this review described the applications of thermal responsive organic materials in smart windows, including poly(N-isopropylacrylamide) (PNIPAm) hydrogels, hydroxypropyl cellulose (HPC) hydrogels, ionic liquids and liquid crystals. Besides, the mechanism of various organic materials and the properties of functional materials were also introduced. Finally, opportunities and challenges relating to thermochromic smart windows and prospects for future development are discussed.

IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. METHODS: Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan-Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. RESULTS: Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan-Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). CONCLUSIONS: Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes' biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

Ablation of lncRNA Miat attenuates pathological hypertrophy and heart failure.

Rationale: The conserved long non-coding RNA (lncRNA) myocardial infarction associate transcript (Miat) was identified for its multiple single-nucleotide polymorphisms that are strongly associated with susceptibility to MI, but its role in cardiovascular biology remains elusive. Here we investigated whether Miat regulates cardiac response to pathological hypertrophic stimuli. Methods: Both an angiotensin II (Ang II) infusion model and a transverse aortic constriction (TAC) model were used in adult WT and Miat-null knockout (Miat-KO) mice to induce pathological cardiac hypertrophy. Heart structure and function were evaluated by echocardiography and histological assessments. Gene expression in the heart was evaluated by RNA sequencing (RNA-seq), quantitative real-time RT-PCR (qRT-PCR), and Western blotting. Primary WT and Miat-KO mouse cardiomyocytes were isolated and used in Ca2+ transient and contractility measurements. Results: Continuous Ang II infusion for 4 weeks induced concentric hypertrophy in WT mice, but to a lesser extent in Miat-KO mice. Surgical TAC for 6 weeks resulted in decreased systolic function and heart failure in WT mice but not in Miat-KO mice. In both models, Miat-KO mice displayed reduced heart-weight to tibia-length ratio, cardiomyocyte cross-sectional area, cardiomyocyte apoptosis, and cardiac interstitial fibrosis and a better-preserved capillary density, as compared to WT mice. In addition, Ang II treatment led to significantly reduced mRNA and protein expression of the Ca2+ cycling genes Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and ryanodine receptor 2 (RyR2) and a dramatic increase in global RNA splicing events in the left ventricle (LV) of WT mice, and these changes were largely blunted in Miat-KO mice. Consistently, cardiomyocytes isolated from Miat-KO mice demonstrated more efficient Ca2+ cycling and greater contractility. Conclusions: Ablation of Miat attenuates pathological hypertrophy and heart failure, in part, by enhancing cardiomyocyte contractility.

Ablation of Sam68 in adult mice increases thermogenesis and energy expenditure.

Genetic deletion of Src associated in mitosis of 68kDa (Sam68), a pleiotropic adaptor protein prevents high-fat diet-induced weight gain and insulin resistance. To clarify the role of Sam68 in energy metabolism in the adult stage, we generated an inducible Sam68 knockout mice. Knockout of Sam68 was induced at the age of 7-10 weeks, and then we examined the metabolic profiles of the mice. Sam68 knockout mice gained less body weight over time and at 34 or 36 weeks old, had smaller fat mass without changes in food intake and absorption efficiency. Deletion of Sam68 in mice elevated thermogenesis, increased energy expenditure, and attenuated core-temperature drop during acute cold exposure. Furthermore, we examined younger Sam68 knockout mice at 11 weeks old before their body weights deviate, and confirmed increased energy expenditure and thermogenic gene program. Thus, Sam68 is essential for the control of adipose thermogenesis and energy homeostasis in the adult.

Sam68 promotes hepatic gluconeogenesis via CRTC2.

Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes.