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Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid-blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.

Emerging studies highlight the Hippo pathway as an important player in organ size control, tissue homeostasis, regeneration, development, and diseases, but our understanding of its roles and regulations remains incomplete. Our recent work reported a functional interplay between the Hippo pathway and heavy metals, providing new insights into this key signaling pathway.

The red panda (Ailurus), a rare and endangered mammal native to the Himalayan–Hengduan Mountains, has a specialized bamboo diet. Combining morphological and genomic evidence, red pandas have been classified as Ailurus fulgens and Ailurus styani. However, previous studies focused on ecological aspects such as foraging behaviors, habitat use and threats within specific distributions; hence, there is still a gap in quantitative comparative studies on the trophic niches of these two species. In this study, we calculated and compared the isotopic trophic niche widths of A. styani and A. fulgens by measuring carbon and nitrogen stable isotopes in hair keratin of 102 red pandas, then conducting a fecal analysis to explore the diet of a population. The results showed that (1) there was no significant difference in δ13C values between A. styani (−24.73 ± 1.26‰, N = 86) and A. fulgens (−24.43 ± 1.20‰, N = 16); however, A. styani had 1.4‰ higher average δ1⁵N value than that of A. fulgens, and the isotopic niche widths converted by Bayesian ellipse model were A. styani SEAC = 4.40‰2, A. fulgens SEAC = 4.70‰2, which might be caused by their lower and narrower altitude distribution. (2) Niche widths of three genetic populations in A. styani were XXL-LS (5.16‰2), EH-GLG (3.40‰2), QL (2.31‰2), and the comparison of the fecal composition suggested their diet diversity, which might imply a degree of competitive pressure with sympatric animals. (3) Sichuan red pandas occupied a lower trophic position compared to other herbivores but higher than giant pandas in the same ecosystem, and the niche width of red pandas was two times larger than that of sympatric giant pandas, which was related to the foraging strategies and microhabitat selection of the giant and red panda. This research provides basic stable isotopic data for red pandas, offers scientific support for the differentiated and refined conservation and management of the red panda and its habitat, and develops the application of stable isotope analysis in the ecological studies of endangered species.

As a key factor in tumorigenesis, progression, recurrence and metastasis, the biological properties, metabolic adaptations and immune escape mechanisms of CSCs are the focus of current oncological research. CSCs possess self-renewal, multidirectional differentiation and tumorigenicity, and their mechanisms of action can be elucidated by the clonal evolution, hierarchical model and the dynamic CSCs model, of which the dynamic model is widely recognized due to its better explanation of the function and origin of CSCs. The origin hypothesis of CSCs involves cell-cell fusion, horizontal gene transfer, genomic instability and microenvironmental regulation, which together shape the diversity of CSCs. In terms of classification, CSCs include primary CSCs (pri-CSCs), precancerous stem cells (pre-CSCs), migratory CSCs (mig-CSCs), and chemo-radiotherapy-resistant CSCs (cr-CSCs and rr-CSCs), with each type playing a specific role in tumor progression. Surface markers of CSCs, such as CD24, CD34, CD44, CD90, CD133, CD166, EpCAM, and LGR5, offer the possibility of identifying, isolating, and targeting CSCs, but the instability and heterogeneity of their expression increase the difficulty of treatment. CSCs have adapted to their survival needs through metabolic reprogramming, showing the ability to flexibly switch between glycolysis and oxidative phosphorylation (OXPHOS), as well as adjustments to amino acid and lipid metabolism. The Warburg effect typifies their metabolic profiles, and altered glutamine and fatty acid metabolism further contributes to the rapid proliferation and survival of CSCs. CSCs are able to maintain their stemness by regulating the metabolic networks to maintain their stemness characteristics, enhance antioxidant defences, and adapt to therapeutic stress. Immune escape is another strategy for CSCs to maintain their survival, and CSCs can effectively evade immune surveillance through mechanisms such as up-regulating PD-L1 expression and promoting the formation of an immunosuppressive microenvironment. Together, these properties reveal the multidimensional complexity of CSCs, underscoring the importance of a deeper understanding of the biology of CSCs for the development of more effective tumor therapeutic strategies. In the future, therapies targeting CSCs will focus on precise identification of surface markers, intervention of metabolic pathways, and overcoming immune escape, with the aim of improving the relevance and efficacy of cancer treatments, and ultimately improving patient prognosis.

Background: There is still no study on the use of the SARC-CalF questionnaire for older critically ill patients. Moreover, there is limited evidence on whether a combination of sarcopenia and frailty can provide incremental improvements in risk stratification for older critically ill patients. Methods: A total of 653 patients older than 60 years were recruited. We used the clinical frailty scale (CFS) and SARC-CalF questionnaire to assess the frailty status and sarcopenia risk, respectively, of older patients shortly after admission to the ICU. The effect of frailty and sarcopenia risk on ICU mortality and 30-day mortality was evaluated. Results: A total of 147 (22.5%) patients died in the ICU, and 187 (28.6%) patients died within 30 days after ICU admission. The CFS score was associated with increased ICU mortality [per 1-score increase: odds ratio (OR) = 1.222, 95% confidential interval (CI): 1.003–1.489] and 30-day mortality (per 1-score increase: OR = 1.307, 95% CI: 1.079–1.583). The SARC-CalF score was also associated with increased ICU mortality (per 1-score increase: OR = 1.204, 95% CI: 1.120–1.294) and 30-day mortality (per 1-score increase: OR = 1.247, 95% CI: 1.163–1.337). The addition of the CFS + SARC-CalF score to Acute Physiology and Chronic Health Evaluation (APACHE) II improved discrimination and reclassified ICU and 30-day mortality risk. Conclusions: Sarcopenia risk assessed by the SARC-CalF questionnaire provided independent prognostic information for older critically ill patients. A combination of sarcopenia and frailty improved the prediction of mortality for older critically ill patients and thus might be useful in the clinical decision-making process.

Surgery is the primary treatment of choice for tumours, and improves prognosis, prolongs survival and is potentially curative. Previous studies have described the effects of anaesthesia and changes in the neuroendocrine, circulatory and sympathetic nervous systems on postoperative cancer progression. There is growing evidence that intraoperative blood loss is an independent prognostic factor for tumour recurrence, postoperative inflammation is a predictor of cancer prognosis, and immunosuppressive status correlates with the degree of surgical damage. This paper outlines the potential mechanisms by which blood loss, surgical trauma and postoperative immunosuppressive status contribute to tumour growth and recurrence by reducing intraoperative haemorrhage and perioperative immunotherapy, thereby reducing tumour growth and recurrence, and improving long-term prognosis.

IntroductionPeach (Prunus persica) has a high nutritional and economic value. However, its overgrowth can lead to yield loss. Regulating the growth of peach trees is challenging. The small auxin-up RNA (SAUR) gene family is the largest family of auxin-responsive genes, which play important roles in plant growth and development. However, members of this gene family are rarely reported in peach.MethodsIn this study, we measured leaf area, chlorophyll and lignin content to detect the role of PpSAUR5 on growth through transgenic Arabidopsis.ResultsPpSAUR5 responds to auxin and gibberellin, promoting and inhibiting the synthesis of gibberellin and auxin, respectively. The heterologous transformation of PpSAUR5 in Arabidopsis led to enhanced growth of leaves and siliques, lightening of leaf color, decrease in chlorophyll content, increase in lignin content, abnormalities in the floral organs, and distortion of the inflorescence axis. Transcriptome data analysis of PpSAUR5 overexpression and wild-type lines revealed 854 differentially expressed genes (DEGs). GO and KEGG analyses showed that the DEGs were primarily involved in biological processes, such as cellular processes, metabolic processes, response to stimuli, and catalytic activity. These genes were mainly enriched in pathways, such as phenylalanine biosynthesis, phytohormone signaling, and MAPK signaling.DiscussionIn summary, these results suggested that PpSAUR5 might regulate tree vigor by modulating the synthesis of auxin and gibberellin. Future studies can use PpSAUR5 as a candidate gene to elucidate the potential regulatory mechanisms underlying peach tree vigor.

Mercury (Hg) is a ubiquitous contaminant in the environment and its methylated form, methylmercury (MeHg), poses a worldwide health concern for humans and wildlife, primarily through fish consumption. Global production of forest fire ash, derived from wildfires and prescribed burns, is rapidly increasing due to a warming climate, but their interactions with aqueous and sedimentary Hg are poorly understood. Herein, we compared the differences of wildfire ash with activated carbon and biochar on the sorption of aqueous inorganic Hg and sedimentary Hg methylation. Sorption of aqueous inorganic Hg was greatest for wildfire ash materials (up to 0.21 μg g-1 or 2.2 μg g-1 C) among all of the solid sorbents evaluated. A similar Hg adsorption mechanism for activated carbon, biochar made of walnut, and wildfire ash was found that involves the formation of complexes between Hg and oxygen-containing functional groups, especially the -COO group. Notably, increasing dissolved organic matter from 2.4 to 70 mg C L-1 remarkably reduced Hg sorption (up to 40% reduction) and increased the time required to reach Hg-sorbent pseudo-equilibrium. Surprisingly, biochar and wildfire ash, but not activated carbon, stimulated MeHg production during anoxic sediment incubation, possibly due to the release of labile organic matter. Overall, our study indicates that while wildfire ash can sequester aqueous Hg, the leaching of its labile organic matter may promote production of toxic MeHg in anoxic sediments, which has an important implication for potential MeHg contamination in downstream aquatic ecosystems after wildfires.

Early embryonic cell fates are specified through coordinated integration of transcription factor activities and epigenetic states of the genome. Foxh1 is a key maternal transcription factor controlling the mesendodermal gene regulatory program. Proteomic interactome analyses using FOXH1 as a bait in mouse embryonic stem cells revealed that FOXH1 interacts with PRC2 subunits and HDAC1. Foxh1 physically interacts with Hdac1, and confers transcriptional repression of mesendodermal genes in Xenopus ectoderm. Our findings reveal a central role of Foxh1 in coordinating the chromatin states of the Xenopus embryonic genome.

Abstract Background This study evaluate the efficacy of part-time patching in preventing recurrence after bilateral lateral rectus recession (BLR) in patients with intermittent exotropia (IXT). Methods A total of 190 children aged 3–13 years who experienced recurrence after BLR for IXT and received part-time patching were retrospectively reviewed. The patching was prescribed for 2 h per day for more than 6 months. Patients who had a recurrence of 18 PD or more underwent reoperation. Changes in exodeviation and reoperation ratio after part-time patching were analyzed. Results A total of 34 patients (17.9%) received reoperation after part-time patching, and the reoperation ratio after 2 years was 20.3% as per the Kaplan–Meier survival analysis. Patients with a recurrence of 7 to 10 PD showed a significantly better effect compared to those with a recurrence of more than 10 PD (p

Abstract Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were −6.7% (SE 0.7) with mazdutide 3 mg, −10.4% (0.7) with 4.5 mg, −11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from −7.7% to −12.3% (all p

The ionospheric F2 critical frequency (foF2) is one of the most crucial application parameters in high-frequency communication, detection, and electronic warfare. To improve the accuracy of spatial reconstruction of the ionospheric foF2, we propose a high-accuracy surface (HAS) modeling method. This method converts difficult-to-solve differential equations into more manageable algebraic equations using direct difference approximation, significantly reducing algorithm complexity and computational load while exhibiting excellent convergence properties. We used seven stations in Brisbane, Canberra, Darwin, Hobart, Learmonth, Perth, and Townsville, with one station as a validation station and six as training stations (e.g., Brisbane as a validation station and the other stations—Canberra, Darwin, Hobart, Learmonth, Perth, and Townsville—as training stations). The training stations and the HAS method were used to train and reconstruct the validation stations at different solar activity periods, seasons, and local times. The predicted values of the validation stations were compared with the measured values, and the proposed method was analyzed and validated. The reconstruction results show the following. (1) The relative root mean square errors (RRMSEs) of HAS method prediction in different solar activity epochs were 13.67%, 7.74%, and 9.19%, respectively, which are 13.57%, 7.41%, and 6.41% higher than the prediction accuracy of the Kriging method, respectively. (2) In the four seasons, the RRMSEs of the HAS method prediction are 9.27%, 13.1%, 8.81%, and 8.09%, respectively, which are 10.83%, 11.73%, 4.25%, and 12.00% higher than the prediction accuracy of the Kriging method. (c) During the daytime and nighttime, the RRMSEs of HAS method prediction were 9.23% and 11.17%, which were 5.92% and 11.99% higher than the prediction accuracy of the Kriging method, respectively. (d) Under the validation dataset, the average predictive RRMSE of the HAS method was 10.29%, and the average predictive RRMSE of the IRI prediction model was 12.35%, with a 2.06% improvement in the predictive accuracy of the HAS method. In general, the prediction effect of the HAS method was better than that of the Kriging method, thus verifying the effectiveness and reliability of the proposed method. In summary, the proposed reconstruction method is of great significance for improving usable frequency prediction and enhancing communication performance.

Mammalian phospholipase D (PLD) enzyme family consists of six members. Among them, PLD1/2/6 catalyzes phosphatidic acid (PA) production, while PLD3/4/5 has no catalytic activities. Deregulation of the PLD-PA lipid signaling has been associated with various human diseases including cancer. However, a comprehensive analysis of the regulators and effectors for this crucial lipid metabolic pathway has not been fully achieved. Using a proteomic approach, we defined the protein interaction network for the human PLD family of enzymes and PA and revealed diverse cellular signaling events involving them. Through it, we identified PJA2 as a novel E3 ubiquitin ligase for PLD1 involved in control of the PLD1-mediated mammalian target of rapamycin signaling. Additionally, we showed that PA interacted with and positively regulated sphingosine kinase 1. Taken together, our study not only generates a rich interactome resource for further characterizing the human PLD-PA lipid signaling but also connects this important metabolic pathway with numerous biological processes.

Heavy metals are both integral parts of cells and environmental toxicants, and their deregulation is associated with severe cellular dysfunction and various diseases. Here we show that the Hippo pathway plays a critical role in regulating heavy metal homeostasis. Hippo signalling deficiency promotes the transcription of heavy metal response genes and protects cells from heavy metal-induced toxicity, a process independent of its classic downstream effectors YAP and TAZ. Mechanistically, the Hippo pathway kinase LATS phosphorylates and inhibits MTF1, an essential transcription factor in the heavy metal response, resulting in the loss of heavy metal response gene transcription and cellular protection. Moreover, LATS activity is inhibited following heavy metal treatment, where accumulated zinc directly binds and inhibits LATS. Together, our study reveals an interplay between the Hippo pathway and heavy metals, providing insights into this growth-related pathway in tissue homeostasis and stress response.

The materials supply for sea islands is the basis for ensuring survival needs of persons on sea islands. Considering factors such as transportation cost, storage cost, recycling demand and transportation capacity, it is a vehicle path planning problem with time window and capacity limit to use many transportation tools to supply materials for sea islands within a time cycle. The intelligent algorithm provides a preferable solution to solve this complex irregular optimization problem. The paper establishes a mathematical model of mission planning of materials supply for sea islands, explores the solving process of genetic algorithm, and uses an example to calculate it. The optimization result shows that the scheme can save transportation costs and storage costs, and also meet the need of materials supply cycle, which can provide a reference for scientific mission planning of materials supply for sea islands.