An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome.

Serial capture affinity purification (SCAP) is a powerful method to isolate a specific protein complex. When combined with cross-linking mass spectrometry and computational approaches, one can build an integrated structural model of the isolated complex. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone reader that recognizes trimethylated histone H3 lysine4 (H3K4me3). In contrast to a previous SCAP analysis of the SPIN1:SPINDOC complex, histones and the H3K4me3 mark were enriched with the WDR76:SPIN1 complex. Next, interaction network analysis of copurifying proteins and microscopy analysis revealed a potential role of the WDR76:SPIN1 complex in the DNA damage response. Since we detected 149 pairs of cross-links between WDR76, SPIN1, and histones, we then built an integrated structural model of the complex where SPIN1 recognized the H3K4me3 epigenetic mark while interacting with WDR76. Finally, we used the powerful Bayesian Integrative Modeling approach as implemented in the Integrative Modeling Platform to build a model of WDR76 and SPIN1 bound to the nucleosome.

The Role of Fc Receptors in the Innate Immune System of Flounders Purported to Be Homologs of FcγRII and FcγRIII.

FcγR is a significant opsonin receptor located on the surface of immune cells, playing a crucial role in Ab-dependent cell-mediated immunity. Our previous work revealed opposite expression trends of FcγRII and FcγRIII in flounder mIgM+ B lymphocytes after phagocytosis of antiserum-opsonized Edwardsiella tarda. This observation suggests that FcγRII and FcγRIII might serve distinct functions in Ig-opsonized immune responses. In this study, we prepared rFcγRIII as well as its corresponding Abs to investigate the potential roles of FcγRII and FcγRIII in the Ab-dependent immune response of IgM+ B cells. Our findings indicate that, unlike FcγRII, FcγRIII does not participate in Ab-dependent cellular phagocytosis. Instead, it is involved in cytokine production and bacterial killing in mIgM+ B lymphocytes. Additionally, we identified platelet-derived ADAM17 as a key factor in regulating FcγRIII shedding and cytokine release in mIgM+ B lymphocytes. These results elucidate the functions of FcγRII and FcγRIII in the innate immunology of mIgM+ B lymphocytes and contribute to an improved understanding of the regulatory roles of FcγRs in the phagocytosis of teleost B lymphocytes.

Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13.

Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named "spautin-1" for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs.

A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

Optimization of Annealing and Metal Films Radiofrequency Heating Procedures for Vitrified Umbilical Arteries.

Vitrification is well known for its application in the cryopreservation of blood vessels, which will address the supply-demand imbalance in vascular grafts for the treatment of cardiovascular disease. Thermal stress damage and devitrification injury in umbilical arteries (UAs) require attention and resolution during the vitrification and rewarming process. In this study, we validated several cooling annealing protocols with temperatures (-130 to -100 °C) and annealing duration durations (10-20 s). Among these, the umbilical artery subjected to annealing at -110 °C for 10 s exhibited the most favorable glass transition and retained 93% of its elastic modulus (0.625 ± 0.030 MPa) compared to the fresh group. Extended annealing temperatures and durations can effectively reduce thermal stress damage, leading to improved mechanical properties by minimizing temperature gradients during cooling. Furthermore, three metal radiofrequency methods were utilized for rewarming, including the use of additional metal films and different magnetic field strengths (20, 25 kA/m). Metal radiofrequency (adding an extra metal film for cryoprotectants rewarming, 20 kA/m) achieved faster and more uniform rewarming, preserving the extracellular matrix (ECM), collagen fibers, and elastic fibers without significant differences compared to the fresh group (P < 0.05). Moreover, its preservation of the biomechanical properties of blood vessels was better than that of water bath heating. Theoretical analysis supports these findings, indicating that radiofrequency heating (RFH) with metal films reduces temperature gradients and thermal stresses during arterial rewarming. RFH contributes to the cryopreservation and clinical application of large-lumen biomaterials, overcoming challenges associated with vascular vitrification and rewarming.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Interleukin-38 promotes skin tumorigenesis in an IL-1Rrp2-dependent manner.

Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL-38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12-dimethylbenzanthracene/12-O-tetradecanoyl phorbol-13-acetate-induced mouse skin tumorigenesis. IL-38 keratinocyte-specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte-specific deletion of IL-38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL-38 is dispensable for epidermal mutagenesis, but IL-38 keratinocyte-specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL-38 activates the c-Jun N-terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer-related inflammatory cytokines and proliferation and migration of tumor cells in an IL-1 receptor-related protein 2 (IL-1Rrp2)-dependent manner. Our findings highlight the role of IL-38 in the regulation of epidermal cell hyperplasia and pro-tumorigenic microenvironment through IL-1Rrp2/JNK and suggest IL-38/IL-1Rrp2 as a preventive and potential therapeutic target in skin cancer.

Parallel genomic responses to historical climate change and high elevation in East Asian songbirds.

Parallel evolution can be expected among closely related taxa exposed to similar selective pressures. However, parallelism is typically stronger at the phenotypic level, while genetic solutions to achieve these phenotypic similarities may differ. For polygenic traits, the availability of standing genetic variation (i.e., heterozygosity) may influence such genetic nonparallelism. Here, we examine the extent to which high-elevation adaptation is parallel-and whether the level of parallelism is affected by heterozygosity-by analyzing genomes of 19 Paridae species distributed across East Asia with a dramatic east-west elevation gradient. We find that western highlands endemic parids have consistently lower levels of heterozygosity-likely the result of late-Pleistocene demographic contraction-than do parids found exclusively in eastern lowlands, which remained unglaciated during the late Pleistocene. Three widespread species (east to west) have high levels of heterozygosity similar to that observed in eastern species, although their western populations are less variable than eastern ones. Comparing genomic responses to extreme environments of the Qinghai-Tibet Plateau, we find that the most differentiated genomic regions between each high-elevation taxon and its low-elevation relative are significantly enriched for genes potentially related to the oxygen transport cascade and/or thermogenesis. Despite no parallelism at particular genes, high similarity in gene function is found among comparisons. Furthermore, parallelism is not higher in more heterozygous widespread parids than in highland endemics. Thus, in East Asian parids, parallel functional response to extreme elevation appears to rely on different genes, with differences in heterozygosity having no effect on the degree of genetic parallelism.

The evolution of ancestral and species-specific adaptations in snowfinches at the Qinghai-Tibet Plateau.

Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai-Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, DTL, we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the DTL gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.

Preimplantation genetic testing for monogenic disorders (PGT-M) offers an alternative strategy to prevent children from being born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes: a retrospective study.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases. MATERIAL AND METHODS: In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers. RESULTS: A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and intellectual developmental disorder (3 families each); Cockayne syndrome (2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy, Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles, the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%; a total of 18 unaffected (i.e., healthy) children were born to these families. CONCLUSIONS: This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.

Effect of online parent training in promoting language development of children with language delay in Hubei province, China.

BACKGROUND: Training parents to implement language and communication intervention strategies is an effective approach to promote language development for children with language delay. AIMS: This study introduces an online parent training program conducted in Hubei province, China, which was designed to help parents of language-delayed children with a diagnosis of autism spectrum disorder (ASD), developmental language disorder (DLD) or global developmental delay (GDD) apply language intervention strategies into daily interactions and promote their children's language development at home. METHODS & PROCEDURES: The Bethel Hearing and Speaking Training Center Family Training for Early Communication & Language Development (Bethel Family Training Program, BFT) (Bethel HSTC, 2020) was designed to improve the language and communication skills for children with language delay in a naturalistic way. The caregivers (including parents, grandparents and other main caregivers) participated in an 8-h online program, including lectures on milestones in child language development, common misunderstandings of child language development, and three basic family language intervention strategies ('Looking together, playing together, and talking together') incorporating active learning through video analysis and discussion. Tongji Hospital in Hubei then continued with 3 months of online home intervention monitoring to all the caregivers via weekly online Q&As led by BFT certified speech therapists' team. The Gesell Developmental Schedules (GDS) was carried out before the online parent training program and after the 3-month online home intervention monitoring. OUTCOMES & RESULTS: 146 families whose children aged 12-68 months with language delay participated in the online training program. The results of the GDS assessments conducted before and after the program showed that not only did the developmental quotient (DQ) of language improve, but so did the DQ of social behaviour and adaptive behaviour (p < 0.001). There is no between-group difference in the application of three strategies between the ASD group and the DLD or GDD group (p > 0.05). Furthermore, both caregivers' ability to apply 'looking together, playing together, talking together' strategies and the effective interaction time played important roles in improving the child's language abilities. CONCLUSION & IMPLICATIONS: The online parent training focusing on improving daily interaction with children through speech-language stimulation strategies promoted the development of language skills. It is an economic and practical approach for children with language delay who have limited access to local language intervention programs. WHAT THIS PAPER ADDS: What is already known on the subject Parent-implemented language intervention is an effective approach at improving children's language development. Telepractice is an appropriate model of service delivery for audiologists and speech-language therapists and may be the primary mode of service delivery or may supplement in-person services. What this paper adds to the existing knowledge This paper explores the effectiveness of an online parent training program and provides new evidence that online training on language support strategies (looking together, playing together, talking together) followed by home intervention monitoring works for Mandarin-speaking children and it is equally effective for children with ASD and non-ASD diagnosis. What are the potential or actual clinical implications of this work? Developmental behavioural paediatricians and speech-language therapists in countries and areas that lack sufficient training resource for every child will have the option to deliver parent training and home intervention monitoring online, which will save time and cost considerably while offering convenience.

A Convenient In Situ Preparation of Cu2ZnSnS4-Anatase Hybrid Nanocomposite for Photocatalysis/Photoelectrochemical Water-Splitting Hydrogen Production.

This study details the rational design and synthesis of Cu2ZnSnS4 (CZTS)-doped anatase (A) heterostructures, utilizing earth-abundant elements to enhance the efficiency of solar-driven water splitting. A one-step hydrothermal method was employed to fabricate a series of CZTS-A heterojunctions. As the concentration of titanium dioxide (TiO2) varied, the morphology of CZTS shifted from floral patterns to sheet-like structures. The resulting CZTS-A heterostructures underwent comprehensive characterization through photoelectrochemical response assessments, optical measurements, and electrochemical impedance spectroscopy analyses. Detailed photoelectrochemical (PEC) investigations demonstrated notable enhancements in photocurrent density and incident photon-to-electron conversion efficiency (IPCE). Compared to pure anatase electrodes, the optimized CZTS-A heterostructures exhibited a seven-fold increase in photocurrent density and reached a hydrogen production efficiency of 1.1%. Additionally, the maximum H2 production rate from these heterostructures was 11-times greater than that of pure anatase and 250-times higher than the original CZTS after 2 h of irradiation. These results underscore the enhanced PEC performance of CZTS-A heterostructures, highlighting their potential as highly efficient materials for solar water splitting. Integrating Cu2ZnSnS4 nanoparticles (NPs) within TiO2 (anatase) heterostructures implied new avenues for developing earth-abundant and cost-effective photocatalytic systems for renewable energy applications.

The role of cannabinoid receptor 2 in bone remodeling during orthodontic tooth movement.

BACKGROUND: The purpose of this study is to explore the effects of CB2 on bone regulation during orthodontic tooth movement. METHODS: Thirty male mice were allocated into 2 groups (n = 15 in each group): wild type (WT) group and CB2 knockout (CB2-/-) group. Orthodontic tooth movement (OTM) was induced by applying a nickel-titanium coil spring between the maxillary first molar and the central incisors. There are three subgroups within the WT groups (0, 7 and 14 days) and the CB2-/- groups (0, 7 and 14 days). 0-day groups without force application. Tooth displacement, alveolar bone mass and alveolar bone volume were assessed by micro-CT on 0, 7 and 14 days, and the number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the expression levels of RANKL and OPG in the compression area were measured histomorphometrically. RESULTS: The WT group exhibited the typical pattern of OTM, characterized by narrowed periodontal space and bone resorption on the compression area. In contrast, the accelerated tooth displacement, increased osteoclast number (P < 0.0001) and bone resorption on the compression area in CB2-/- group. Additionally, the expression of RANKL was significantly upregulated, while OPG showed low levels in the compression area of the CB2 - / - group (P < 0.0001). CONCLUSIONS: CB2 modulated OTM and bone remodeling through regulating osteoclast activity and RANKL/OPG balance.

Effects of SvAPETALA1-5 gene on floral organ development in Senecio vulgaris.

Asteraceae is a large class of eudicots with complex capitulum, and little is known regarding the molecular regulation mechanism of flower development. APETALA1(AP1) belongs to the MADS-box gene family and plays a key role in plant floral induction and floral organ development. In this study, the bioinformatics and tissue-specific expression of AP1 homologous gene SvAP1-5 in Senecio vulgaris were analyzed. Based on VIGS technology, SvAP1-5 gene silencing plants were created, and SvAP1-5 was overexpressed in Solanum nigrum. The results of bioinformatics analysis showed that SvAP1-5 gene had typical MADS-box and K-box structure, and contains FUL motif and paleoAP1 motif at the C-terminal. SvAP1-5 belongs to the euFUL branch of AP1 gene. qRT-PCR results showed that SvAP1-5 was expressed in bracts, petals and carpels, and was highly expressed in carpels. Compared with the control group, SvAP1-5 gene silencing resulted in irregular petal dehiscence, increased stigma division, and carpel dysplasia. The fruit development of SvAP1-5 overexpressing S.nigrum plants was abnormal, and the hyperplastic tissue similar to fruit appeared. In summary, SvAP1-5 gene may be involved in the development of petals and carpels and plays an important role during the development of S.vulgaris.

Multivalent Weak Protections Ultimately Enable Customizable DNA Grafting on Pristine Ag Colloids for Nanoplasmonics.

Silver nanoparticles (AgNPs) have superior plasmonic properties surpassing other metals. However, a long-standing difficulty in valence/density-tunable DNA grafting of AgNPs disfavors their use in DNA-directed nanoplasmonics. Herein a close-to-ideal surface protection of pristine AgNPs against various notorious stability issues of Ag is achieved based on multidentate weak nucleobase bindings of non-programming FSDNA (fish sperm DNA). This further allows grafting of thiolated DNA with tunable valence/density on AgNPs. The end-on format of the thiolated DNA grafts and the very thin FSDNA layer benefit DNA hybridization and plasmon coupling, respectively. Significantly promoted optical coupling and Raman enhancing are achieved. The compatibility of FSDNA-capped AgNPs with Au enables DNA-bonded symmetry-broken Au-Ag heterodimers with strong near-field coupling and an easily seen Fano-induced feature. Our work provides a treasured freedom of using AgNPs in DNA-programmed, better-behaving plasmonic devices.

Asymmetric Total Synthesis of Euphordraculoate A and Pedrolide.

Here we report the asymmetric total syntheses of two rearranged tigliane diterpenoids, euphordraculoate A and pedrolide. A reductive dihydroxylation cascade and Nazarov cyclization were performed to generate euphordraculoate A, which was subjected to a cascade of Eu-promoted dienyl enolization, intramolecular Diels-Alder reaction and enol-ketone tautomerization to afford pedrolide, a pathway consistent with our proposal for the biogenesis of pedrolide.

Ultralarge Pixel Array Photothermal Film based on 3D Self-Suspended Microbridge Structure for Infrared Scene Projection.

Infrared emitter is highly desirable for applications in infrared imaging and infrared stealth technology. It is also a core device in infrared scene generation. Light-driven photothermal film has attracted considerable interest due to its outstanding photothermal properties and easy fabrication. However, the existing photothermal films suffer from low photothermal conversion efficiency (PCE) as well as small sizes. The improvement of the PCE is usually achieved at the expense of dynamic frame rate. Here, this work designs and fabricates a photothermal film based on 3D self-suspended microbridge structure. Silicon (Si) microbridges are introduced into each microstructure to manipulate the thermal conductivity of the films. By optimizing the parameters of the Si microbridges, the high PCE and fast frame rate are both achieved. Moreover, the 3D structure microbridge film is 4-inch in diameter, forming an ultralarge array with over 2200 × 2200 pixels. Finally, a high PCE infrared scene projector is realized based on this photothermal film. A visible image is projected on the film, the 3D-microstructured photothermal film absorbs the visible light and emits an infrared image same as the visible one with high resolution and fast frame rate due to the excellent photothermal properties.

Akkermansia muciniphila plays critical roles in host health.

Akkermansia muciniphila, an intestinal microorganism, belongs to Verrucomicrobia, one of the most abundant microorganisms in the mammalian gut. It is a mucin-degrading bacterium that can colonise intestines of mammals such as humans and mice by utilising mucin as the only nitrogen and carbon source. When A. muciniphila colonises the intestine, its metabolites interact with the intestinal barrier, affecting host health by consolidating the intestinal barrier, regulating metabolic functions of the intestinal and circulatory systems, and regulating immune functions. This review summarised the mechanisms of A. muciniphila-host interactions that are relevant to host health. We focussed on characteristics of A. muciniphila in relation to its metabolites to provide a comprehensive understanding of A. muciniphila and its effects on host health and disease processes.

Divergent contributions of coding and noncoding sequences to initial high-altitude adaptation in passerine birds endemic to the Qinghai-Tibet Plateau.

Early events in the evolution of an ancestral lineage can shape the adaptive patterns of descendant species, but the evolutionary mechanisms driving initial adaptation from an ancestor remain largely unexplored. High-altitude adaptations have been extensively explored from the viewpoint of protein-coding genes; however, the contribution of noncoding regions remains relatively neglected. Here, we integrate genomic and transcriptomic data to investigate adaptive evolution in the ancestor of three high-altitude snowfinch species endemic to the Qinghai-Tibet Plateau. Our genome-wide scan for adaptation in the snowfinch ancestor identifies strong adaptation signals in functions of development and metabolism for the coding genes, but in functions of the nervous system development for noncoding regions. This pattern is exclusive to the snowfinch ancestor compared to a control ancestral lineage subject to weak selection. Changes in noncoding regions in the snowfinch ancestor, especially those nearest to coding genes, may be disproportionately associated with the differential expression of genes in the brain tissue compared to other tissues. Extensive gene expression in the brain tissue can be further altered via genetic regulatory networks of transcription factors harbouring potential accelerated regulatory regions (e.g., the development-related transcription factor YEATS4). Altogether, our study provides new evidence concerning how coding and noncoding sequences work through decoupled pathways in initial adaptation to the selective pressure of high-altitude environments. The analysis highlights the idea that noncoding sequences may be promising elements in facilitating the rapid evolution and adaptation to high altitudes.

Metabolic Changes in Cardiac Aging.

Cardiac aging is a natural process accompanied by cardiomyocyte hypertrophy and dysfunction. These changes can lead to adverse organ remodeling and ultimately lead to the development of heart failure. The study of cardiac aging is helpful to explore the mechanism of senescence and is of great significance for preventing cardiac aging. Cardiac aging is accompanied by changes in various metabolic functions. In this process, due to the change of metabolic substrates and enzyme activities, oxidative stress response increases, and reactive oxygen species (ROS) increases, accompanied by mitochondrial dysfunction and gene expression changes, so related protein metabolism also changes. Hormone metabolism and autophagy are also involved in the process of cardiac aging. Based on these findings, changes in diet, caloric restriction, improvement of mitochondrial function and promotion of autophagy have been proven to have positive effects in delaying cardiac aging. This article reviews the metabolic changes involved in the process of cardiac aging from different aspects, and briefly reviews the measures to improve cardiac aging.