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Metal implants are commonly used in clinical practice. However, little is known regarding the prevalence of metal implants. Therefore, this study aimed to evaluate the prevalence of metal implants in the United States (US) among individuals aged ≥ 40 years. This study conducted a serial cross-sectional analysis of US adults aged ≥ 40 years who participated in the National Health and Nutrition Examination Survey (NHANES) (2015-2016 and 2017-March 2020). Self-reported questionnaires were used to assess whether the participants had metal implants inside their bodies. The primary outcome was the prevalence of metal implants among adults aged 40 years and older. Furthermore, weighted logistic regression analysis was employed to determine the changes in the prevalence of metal implants from 2015 to March 2020. Moreover, this study investigated the variation in metal implant prevalence by demographic factors based on the pooled NHANES cycles. All analyses were conducted based on 3,736 participants from the NHANES 2015-2016 and 6,387 participants from the NHANES 2017-March 2020. This study observed a high prevalence of metal implants among adults aged 40 and older (2015-2016: 27.23%; 2017-March 2020: 31.53%). Moreover, the results of the weighted logistic regression analysis showed that the prevalence of metal implants significantly increased from 2015 to March 2020, especially among older individuals, men, and White individuals. In addition, the results of the weighted logistic regression analysis indicated that the metal implant prevalence differed by age and race/ethnicity, in which older individuals and White individuals showed a significantly higher prevalence of metal implants than younger individuals and non-White individuals, respectively. There was a high prevalence of metal implants among US adults aged 40 and older, and the prevalence of metal implants significantly increased from 2015 to March 2020. Therefore, more attention needs to be paid to this special population, and it may be necessary to ensure accessibility and affordability and assess the potential long-term health impacts of metal implants, considering the increased prevalence of metal implants., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Projections of future income distributions at subnational levels are becoming increasingly important for a variety of analyses and evaluations. However, relevant datasets are currently limited. This study presents a methodological framework that introduces machine learning algorithms to a top-down approach used for generating income distribution datasets. We project per capita disposable income and income inequality for 31 Chinese provinces from 2020 to 2100, considering different scenarios based on China's local circumstances, and then estimate income distributions based on these. After accounting for necessary consistency between provincial, urban, and rural income datasets, we further generate the same data products at the urban and rural level for each province. We validate our projection results drawing on data from 2007-2023 for China's disposable income, data from 2007 to 2019 for provincial income inequality in China, as well as national income inequality data for the past 20 to 60 years from select developed countries. The proposed methodology provides flexibility to generate similar data products according to a user's specific needs. Our resulting datasets have several potential applications and can serve as inputs for research on drivers and impacts across social, economic, and environmental domains., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Studies on the association between dietary inflammatory index (DII) and chronic kidney disease (CKD) are limited. We aimed to examine the association between DII and CKD among U.S. adults with particular attention paid to sex differences. A total of 19317participants were included in this study. The exposure variable was DII, which was calculated based on overall inflammatory effect scores. The outcome was CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 or urinary albumin/creatinine (uACR) ≥ 30 mg/g. The mean (SD) of age our study participants was 47.84 (18.35); and the mean (SD) of DII was 1.50 (1.91) (median 1.74). In multivariate logistic regression analysis, we observed that the OR value (95%CI) of CKD is 1.19 (1.14, 1.23), 1.12 (1.06, 1.19), and 1.16 (1.06, 1.27) in models 1, 2 and 3 for Per SD increment of DII. Compared with Participants with Q1(DII < 0.15), the adjusted ORs for participants in Q2 (0.15 ≤ DII < 1.74), Q3 (1.74 ≤ DII < 3.02) and Q4 (≥ 3.02)were 1.46 (95% CI 1.14-1.88), 1.55 (95% CI 1.20-1.99) and 1.52 (95% CI 1.17, 1.98) ( p for trend < 0.05), respectively. However, this study observed that the independent positive correlation between DII and CKD appeared in women rather than men. Higher DII levels were significantly and linearly associated with an increased prevalence of chronic kidney disease, and sex modified the association. This suggests that gender-specific dietary interventions can be developed to reduce the risk of CKD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: All procedures performed in studies involving human participants were following the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants provided written informed consent. And this survey was approved by the Ethics Review Board of the National Center for Health Statistics. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 - May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 - January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848-0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836-0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868-0.953) and 0.951 (95% CI: 0.924-0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the "DELPHI" consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). "Nomogram-10" provides clinicians with a practical tool to develop personalized intervention strategies based on an individual's risk profile.Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852., (© 2024. The Author(s).)

The toxicity of lunar dust (LD) to astronauts' health has been confirmed in the Apollo missions and subsequent biological experiments. Therefore, it is crucial to understand the biological toxicity of lunar dust for future human missions to the Moon. In this study, we exposed human lung epithelial cells (BEAS-2B) and peripheral blood B lymphocytes (AHH-1) to varying concentrations (0, 500, 1000, and 1500 μg/ml) of a lunar dust simulant (LDS) called CLDS-i for 24 and 48 h. The results provided the following key findings: (1) LDS induction of cell damage occurred through oxidative stress, with the levels of reactive oxygen species (ROS) in BEAS-2B cells being dependent on the duration of exposure. (2) Necrosis and early apoptosis were observed in BEAS-2B cells and AHH-1 cells, respectively. In addition, both cells showed lysosomal damage. (3) Genes CXCL1, SPP1, CSF2, MMP1, and POSTN are implicated in immune response and cytoskeletal arrangement regulation in BEAS-2B cells. Considering the similarities in composition and properties between CLDS-i and real lunar dust, our findings not only enhance the understanding of LDS toxicity, but also contribute to a better comprehension of the genomic alterations and molecular mechanisms underlying cellular toxicity induced by LD. These insights will contribute to the development of a biotoxicology framework aimed at safeguarding the health of astronauts and, consequently, facilitating future human missions to the Moon., (© 2024. The Author(s).)

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases., (© 2024. The Author(s).)

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 10 9 /L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na + currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na + /Ca 2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca 2+ -optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD 80 ), Ca 2+ transient peak signals and durations at 80% recovery (CaTD 80 ), times to peak Ca 2+ (TTP 100 ) and Ca 2+ decay constants (Decay 30-90 ) during regular 10-Hz stimulation, and Ca 2+ transient alternans with shortening cycle length. Isoproterenol shortened APD 80 in sham-operated and TAC-only hearts, shortening CaTD 80 and Decay 30-90 but sparing TTP 100 and Ca 2+ transient alternans in all groups. All groups showed similar APD 80 , and TAC-only hearts showed greater CaTD 80 , heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca 2+ homeostatic, and pro-arrhythmogenic changes in intact hearts., (© 2024. The Author(s).)

In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2-200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2-200 kb targets using a short-read sequencer., (© 2024. The Author(s).)

In order to explore relationship of ambulatory blood pressure monitoring (ABPM) and soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) in suspected preeclampsia(PE), suspected PE participants in 28 + 0 to 33 + 6 weeks underwent ABPM and sFlt-1/PlGF from July 2020 to July 2022 were included(N = 476) in study. ABPM parameters were compared between sFlt-1/PlGF ≥38 and <38 groups. Correlation analysis was performed between ABPM and sFlt-1/PlGF, and logistic regression was used to explore prediction value for PE in 2 weeks. One hundred eighteen cases developed PE in 2 weeks with 114 from sFlt-1/PlGF ≥38 group. Daytime and nighttime BP were all increased,with increased non-dipper (58.4% vs. 30.3%), riser (22.1% vs. 13.1%) and and decreased Dipper (15.4% vs. 45.9%) type of ABPM in sFlt-1/PlGF ≥38 groups (P < 0.05).The riser group had the highest sFlt-1 and lowest PlGF. sFlt-1/PlGF and sFlt-1 were all positively correlated with systolic (SBP) & diastolic blood pressure(DBP)(P < 0.01), in which correlation coefficients of daytime and nighttime BP with sFlt-1 were β = 150.05 & 157.67 for SBP, β = 234 and 199.01 for DBP, respectively. However, PlGF was only negatively associated with nighttime SBP and DBP(P < 0.05), with no correlation with daytime BP (P > 0.05).Combining sFlt-1/PlGF and ABPM model, showed sFlt-1/PlGF (aOR = 2.01 (1.69-2.36)), Nighttime DBP (aOR = 1.14 (1.02-1.28)) contributed to preeclampsia prediction, and had improved predictive value compared to ABPM or sFlt-1/PlGF models alone(P < 0.05). sFlt-1/PlGF ratio was positively correlated with BP parameters, whereas PIGF was only negatively correlated with nocturnal BP and increased non-dipper type change in ABPM, which had a synergistic effect with sFlt-1/PlGF on PE prediction., (© 2023. The Author(s).)

Depending on the source of the blastophore, there are various subtypes of laryngeal cancer, each with a unique metastatic risk and prognosis. The forecasting of their prognosis is a pressing issue that needs to be resolved. This study comprised 5953 patients with glottic carcinoma and 4465 individuals with non-glottic type (supraglottic and subglottic). Five clinicopathological characteristics of glottic and non-glottic carcinoma were screened using univariate and multivariate regression for CoxPH (Cox proportional hazards); for other models, 10 (glottic) and 11 (non-glottic) clinicopathological characteristics were selected using least absolute shrinkage and selection operator (LASSO) regression analysis, respectively; the corresponding survival models were established; and the best model was evaluated. We discovered that RSF (Random survival forest) was a superior model for both glottic and non-glottic carcinoma, with a projected concordance index (C-index) of 0.687 for glottic and 0.657 for non-glottic, respectively. The integrated Brier score (IBS) of their 1-year, 3-year, and 5-year time points is, respectively, 0.116, 0.182, 0.195 (glottic), and 0.130, 0.215, 0.220 (non-glottic), demonstrating the model's effective correction. We represented significant variables in a Shapley Additive Explanations (SHAP) plot. The two models are then combined to predict the prognosis for two distinct individuals, which has some effectiveness in predicting prognosis. For our investigation, we established separate models for glottic carcinoma and non-glottic carcinoma that were most effective at predicting survival. RSF is used to evaluate both glottic and non-glottic cancer, and it has a considerable impact on patient prognosis and risk factor prediction., (© 2024. The Author(s).)

An unexpected surge of osteoporosis outpatients occurred after COVID-19 lockdown was lifted in China. To confirm the observation and identify possible reasons driving patients care seeking behaviors post-pandemic, we compared the outpatient volumes at the osteoporosis clinic in January through May, 2019-2022 and surveyed seven osteoporosis specialists across China to validate the phenomenon before devising an online questionnaire to collect patients' characters and physical activity levels. Univariate and binary logistic regression analyses were calculated to identify predictors of post-lockdown care-seeking. We received 480 valid responses, including 397 (82.7%) patients having visited the clinic after lockdown and 83 (17.3%) having not. Four significant predictors were identified, including being female, experiencing pain, aggravating symptoms, and heightened anxiety during lockdown (P < 0.05). Both groups experienced lower physical activity levels during lockdown, which however was not a significant predictor (P = 0.317). The surge in osteoporosis outpatient visits after COVID-19 lockdown suggests vast latent demand for osteoporosis care accumulated during the pandemic. Four significant factors predict post-lockdown outpatient care-seeking, including being female, experiencing pain and aggravating symptoms, and heightened anxiety levels. Though physical activity levels decreased during lockdown, it failed to predict care-seeking. This demonstrates resilience of osteoporosis patients to resume regular care despite disruption and stress the substantial backlog of unmet healthcare needs., (© 2024. The Author(s).)

A total of 40 fiber reinforced polymer (FRP) and polyvinyl chloride (PVC) confined spontaneous combustion gangue coarse-aggregate concrete (SAC) specimens were subjected to axial compression tests and theoretical studies. The main analysis focused on the impact of the replacement rate of spontaneous combustion gangue (SCG), the type of CFRP confinement, and the number of CFRP layers on the axial compression performance of CFRP-PVC confined SAC (CFRP-PVC-SAC). The results show that CFRP-PVC confinement can effectively enhance the axial compressive capacity, axial deformation, and lateral deformation of the components. The increase in strength ranges from 1.68 to 3.48 times, while the increase in strain ranges from 5.21 to 11.98 times. The crack patterns and expansive behavior of the coal gangue concrete under confinement exhibit significant differences compared to ordinary concrete. In addition, based on the framework of the existing FRP-confined plain concrete model, a modified model is established to facilitate prediction of stress-strain relationships for short columns of CFRP-PVC-SAC, with the calculated results in good agreement with experimental values., (© 2024. The Author(s).)

The Asian ladybeetle, Coccinella septempunctata, is an important insect of predatory natural enemy, which has a strong control effect and application prospects for aphids, whiteflies, mealybugs, and other small-sized pests of agriculture and forestry crops. Gut microbiota composition posed impacts on development of insects. In order to clarify the effect of artificial feed feeding on the intestinal microbial species and structure of C. septempunctata, we compared the intestinal microbial flora of C. septempunctata reared on bean aphids and artificial food for 15 days. Results show that Proteobacteria was the dominant component in all groups at phylum level, Rhodobacter, Methylovigula, Burkholderia, and Bradyrhizobium were the dominant bacteria among all groups at genus level. As to the differences in bacterial community structure and diversity, there is no significant difference between Shannon index and Simpson index, the principal components analysis of the bacterial communities, and the samples were roughly distributed in different regions. After 15 days of feeding, artificial diet did not significantly reduce the microbial diversity of the gut of C. septempunctata compared to the aphid group, and there was no significant effect on the abundance of dominant flora in the gut of C. septempunctata, C. septempunctata gut has a similar core microbiota. This study clarifies the effects in intestinal microbial diversity and composition structure of the C. septempunctata with artificial diet, and provides a theoretical basis for understanding the intestinal microorganisms and optimizating the artificial diet of C. septempunctata., (© 2024. The Author(s).)

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target., (© 2023. The Author(s).)

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cities play a fundamental role in policy decision-making processes, necessitating the availability of city-level population projections to better understand future population dynamics and facilitate research across various domains, including urban planning, shrinking cities, GHG emission projections, GDP projections, disaster risk mitigation, and public health risk assessment. However, the current absence of city-level population projections for China is a significant gap in knowledge. Moreover, aggregating grid-level projections to the city level introduces substantial errors of approximately 30%, leading to discrepancies with actual population trends. The unique circumstances of China, characterized by comprehensive poverty reduction, compulsory education policies, and carbon neutrality goals, render scenarios like SSP4(Shared Socioeconomic Pathways) and SSP5 less applicable. To address the aforementioned limitations, this study made three key enhancements, which significantly refines and augments our previous investigation. Firstly, we refined the model, incorporating granular demographic data at the city level. Secondly, we redesigned the migration module to consider both regional and city-level population attractiveness. Lastly, we explored diverse fertility and migration scenarios., (© 2023. The Author(s).)

The development of the cardiac conduction system (CCS) is essential for correct heart function. However, critical details on the cell types populating the CCS in the mammalian heart during the development remain to be resolved. Using single-cell RNA sequencing, we generated a large dataset of transcriptomes of ~0.5 million individual cells isolated from murine hearts at six successive developmental corresponding to the early, middle and late stages of heart development. The dataset provides a powerful library for studying the development of the heart's CCS and other cardiac components. Our initial analysis identified distinct cell types between 20 to 26 cell types across different stages, of which ten are involved in forming the CCS. Our dataset allows researchers to reuse the datasets for data mining and a wide range of analyses. Collectively, our data add valuable transcriptomic resources for further study of cardiac development, such as gene expression, transcriptional regulation and functional gene activity in developing hearts, particularly the CCS., (© 2023. Springer Nature Limited.)

The utilization rate of water resources of mines in China is still relatively low. The evaluation of mine water recycling has practical guiding significance for the planning, positioning, development, and construction of groundwater in today's society. This article constructs an evaluation system for mine water recycling based on the key performance index (KPI) via the Internet of Things and big data platforms. This system evaluates the recycling status of mine water. First, the micro-seismic monitoring system and the hydrological dynamic detection system are deployed in work. The installation and debugging methods are compared to meet the monitoring requirements. Second, the filtered clear water is used for equipment cooling and firefighting dust removal at the mining face through the constant pressure supply pump. The excess clear water is discharged to the surface. Finally, 16 indicators are screened from four dimensions to construct a key KPI mine water evaluation system for evaluation and optimization. The results demonstrate that the first mine water monitoring system runs well and is fully functional, achieving the expected goal. The utilization rate evaluation score has increased yearly, from 3.05 points in 2016 to 3.39 points in 2020. However, the per capita utilization rate score still needs improvement. It is essential to improve the rationality of development and utilization., (© 2023. The Author(s).)

Quantum emitters coupled to optical resonators are quintessential systems for exploring fundamental phenomena in cavity quantum electrodynamics (cQED) 1 and are commonly used in quantum devices acting as qubits, memories and transducers 2 . Many previous experimental cQED studies have focused on regimes in which a small number of identical emitters interact with a weak external drive 3-6 , such that the system can be described with simple, effective models. However, the dynamics of a disordered, many-body quantum system subject to a strong drive have not been fully explored, despite its importance and potential in quantum applications 7-10 . Here we study how a large, inhomogeneously broadened ensemble of solid-state emitters coupled with high cooperativity to a nanophotonic resonator behaves under strong excitation. We discover a sharp, collectively induced transparency (CIT) in the cavity reflection spectrum, resulting from quantum interference and collective response induced by the interplay between driven inhomogeneous emitters and cavity photons. Furthermore, coherent excitation within the CIT window leads to highly nonlinear optical emission, spanning from fast superradiance to slow subradiance 11 . These phenomena in the many-body cQED regime enable new mechanisms for achieving slow light 12 and frequency referencing, pave a way towards solid-state superradiant lasers 13 and inform the development of ensemble-based quantum interconnects 9,10 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Nocturnal scratch is one major factor leading to impaired quality of life in atopic dermatitis (AD) patients. Therefore, objectively quantifying nocturnal scratch events aids in assessing the disease state, treatment effect, and AD patients' quality of life. In this paper, we describe the use of actigraphy, highly predictive topological features, and a model-ensembling approach to develop an assessment of nocturnal scratch events by measuring scratch duration and intensity. Our assessment is tested in a clinical setting against the ground truth obtained from video recordings. The new approach addresses unmet challenges in existing studies, such as the lack of generalizability to real-world applications, the failure to capture finger scratches, and the limitations in the evaluation due to imbalanced data in the current literature. Furthermore, the performance evaluation shows agreement between derived digital endpoints and the video annotation ground truth, as well as patient-reported outcomes, which demonstrated the validity of the new assessment of nocturnal scratch., (© 2023. The Author(s).)

Under the creep action of composite steel and concrete beams reinforced by carbon-fiber-reinforced polymer (CFRP) sheet, the face of the CFRP sheet, steel beam, and concrete slab beam produce relative slip. This slip affects the interface interaction, reduces the bearing capacity and stiffness of the members, and increases the deformation. In this paper, elastic and energy methods are used to analyze the interface forces between steel beams and concrete slabs reinforced by CFRP sheeting under the action of concrete creep. The calculation formulas for interface slip, axial force, and incremental deformation are established. The influence of design parameters on the mechanical properties of the interface is analyzed. Results show that the increments in interface slip, axial force, and deformation are zero on the 28th day. With increasing age, the increments in interface slip, axial force, and deformation gradually increase, and the increase is large in the first 100 days; it basically remains unchanged during the time interval from 100 to 1028 days. When the load increases by 5 N/mm (5 kN), the slip increments increase by approximately 0.004 mm, 0.002 mm, and 0.002 mm. The increments in axial force are approximately 19.4 kN, 15.9 kN, and 16.1 kN. The deformation increments increase by approximately 1.7 mm, 1.1 mm, and 0.6 mm., (© 2022. The Author(s).)

Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Optical mapping of animal models is a widely used technique in pre-clinical cardiac research. It has several advantages over other methods, including higher spatial resolution, contactless recording and direct visualisation of action potentials and calcium transients. Optical mapping enables simultaneous study of action potential and calcium transient morphology, conduction dynamics, regional heterogeneity, restitution and arrhythmogenesis. In this dataset, we have optically mapped Langendorff perfused isolated whole hearts (mouse and guinea pig) and superfused isolated atria (mouse). Raw datasets (consisting of over 400 files) can be combined with open-source software for processing and analysis. We have generated a comprehensive post-processed dataset characterising the baseline cardiac electrophysiology in these widely used pre-clinical models. This dataset also provides reference information detailing the effect of heart rate, clinically used anti-arrhythmic drugs, ischaemia-reperfusion and sympathetic nervous stimulation on cardiac electrophysiology. The effects of these interventions can be studied in a global or regional manner, enabling new insights into the prevention and initiation of arrhythmia., (© 2022. The Author(s).)

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma 1-4 . Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial 5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries 6 . Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively 7-11 . Treatment combining 1 mg kg -1 nivolumab with 3 mg kg -1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer 12 . Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma., (© 2022. The Author(s).)

Pathological hypertrophy underlies sudden cardiac death due to its high incidence of occurrence of ventricular arrhythmias. The alteration of transmural electrophysiological properties in hypertrophic cardiac murine tissue has never been explored previously. In this dataset, we have for the first time conducted high-throughput simultaneous optical imaging of transmembrane potential and calcium transients (CaT) throughout the entire hypertrophic murine hearts at high temporal and spatial resolution. Using ElectroMap, we have conducted multiple parameters analysis including action potential duration/calcium transient duration, conduction velocity, alternans and diastolic interval. Voltage-calcium latency was measured as time difference between action potential and CaT peak. The dataset therefore provides the first high spatial resolution transmural electrophysiological profiling of the murine heart, allowing interrogation of mechanisms driving ventricular arrhythmias associated with pathological hypertrophy. The dataset allows for further reuse and detailed analyses of geometrical, topological and functional analyses and reconstruction of 2-dimensional and 3-dimentional models., (© 2021. Crown.)

Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer-template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer-template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis., (© 2021. The Author(s).)

Many pathogenic fungi depend on the development of specialized infection structures called appressoria to invade their hosts and cause disease. Impairing the function of fungal infection structures therefore provides a potential means by which diseases could be prevented. In spite of this extraordinary potential, however, relatively few anti-penetrant drugs have been developed to control fungal diseases, of either plants or animals. In the present study, we report the identification of compounds that act specifically to prevent fungal infection. We found that the organization of septin GTPases, which are essential for appressorium-mediated infection in the rice blast fungus Magnaporthe oryzae, requires very-long-chain fatty acids (VLCFAs), which act as mediators of septin organization at membrane interfaces. VLCFAs promote septin recruitment to curved plasma membranes and depletion of VLCFAs prevents septin assembly and host penetration by M. oryzae. We observed that VLCFA biosynthesis inhibitors not only prevent rice blast disease, but also show effective, broad-spectrum fungicidal activity against a wide range of fungal pathogens of maize, wheat and locusts, without affecting their respective hosts. Our findings reveal a mechanism underlying septin-mediated infection structure formation in fungi and provide a class of fungicides to control diverse diseases of plants and animals.

Herein, we report two female cases with novel nonsense mutations of STAG2 at Xq25, encoding stromal antigen 2, a component of the cohesion complex. Exome analysis identified c.3097 C>T, p.(Arg1033*) in Case 1 (a fetus with multiple congenital anomalies) and c.2229 G>A, p.(Trp743*) in Case 2 (a 7-year-old girl with white matter hypoplasia and cleft palate). X inactivation was highly skewed in both cases., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Ethylene-triggered flowering is a common phenomenon in plants of the family Bromeliaceae, but its molecular mechanism remains unclear. As a classical group of small RNAs, microRNAs play an essential role in the regulation of flowering. In this study, we found that various miRNAs participate in the ethylene-triggered flowering process in Aechmea fasciata via small RNA sequencing using juvenile and adult plants treated with ethylene for 24 hours. Finally, 63 known miRNAs, 52 novel miRNAs and 1721 target genes were identified or predicted. Expression changes of specific miRNAs were validated by qRT-PCR and northern blotting. Some predicted targets, including SPL, GAMYB and ARF, were verified in RLM-RACE experiments. Gene Ontology (GO) and KEGG analysis showed that numerous developmental and RNA-related processes were enriched. Integrated analysis of the transcriptomic data with small RNA sequencing revealed that numerous miRNAs and targets involved in ethylene-triggered flowering in A. fasciata. Our study is helpful for illuminating the molecular basis of the ethylene-triggered flowering phenomenon in Bromeliaceae.

GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several psychiatric disorders 1,2 . Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric G s protein 2 , but it is unclear how GPR52 and G s couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a G s -coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR52 3 . A fully active state is achieved when G s is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52.

Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development 1-6 . The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities 7-9 . Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown 10-12 . Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.

The engineering of immunoglobulin-G molecules (IgGs) is of wide interest for improving therapeutics, for example by modulating the activity or multiplexing the specificity of IgGs to recognize more than one antigen. Optimization of engineered IgG requires knowledge of three-dimensional (3D) structure of synthetic IgG. However, due to flexible nature of the molecules, their structural characterization is challenging. Here, we use our reported individual-particle electron tomography (IPET) method with optimized negative-staining (OpNS) for direct 3D reconstruction of individual IgG hole-hole homodimer molecules. The hole-hole homodimer is an undesired variant generated during the production of a bispecific antibody using the knob-into-hole heterodimer technology. A total of 64 IPET 3D density maps at ~15 Å resolutions were reconstructed from 64 individual molecules, revealing 64 unique conformations. In addition to the known Y-shaped conformation, we also observed an unusual X-shaped conformation. The 3D structure of the X-shaped conformation contributes to our understanding of the structural details of the interaction between two heavy chains in the Fc domain. The IPET approach, as an orthogonal technique to characterize the 3D structure of therapeutic antibodies, provides insight into the 3D structural variety and dynamics of heterogeneous IgG molecules.

The reclaimed soil properties of industrial and mining wasteland have strong spatial specificity. The paper aimed to screen out a hybrid multifractal and kriging (Named as Mkriging) method for digital mapping and scientifically reveal the spatial distribution characteristics in view of heavy metal in reclaimed soil of industrial and mining abandoned land. The results of the study showed that for reasons of history and reclamation, the original samples of heavy metals in reclaimed soil of industrial and mining abandoned land showed a very large range and variation degree, the C 0 /(C 0  + C 1 ) values of different heavy metals basically were all greater than 50%, random factors played a dominant role. The five kinds of heavy metals in reclaimed soil were in the following descending order in terms of homogeneity: Cd, As, Hg, Ni and Cr. Compared with ordinary Kriging method, the relative improvement of root mean squared errors of elements Cd, Hg, As, Cr and Ni based on Mkriging were 95.28%, 61.74%, 78.54%, 82.51% and 83.58% respectively. The higher the fractal degree of heavy metals in reclaimed soil was, the higher the prediction accuracy will be. Mkriging method is more suitable for spatial prediction of heavy metals in reclaimed soil of industrial and mining abandoned land.

Prepulse inhibition (PPI) is the suppression of the startle reflex when the intense startling stimulus is shortly preceded by a weaker non-startling stimulus (prepulse). In rats, the auditory precedence-effect-induced perceived spatial separation between the fear-conditioned prepulse and a noise masker facilitates selective attention to the prepulse and enhances PPI. However, whether the perceptual separation between the prepulse and a noise masker can also enhance PPI in humans remains unclear. Also, the relationship between the PPI enhancement and the change in early cortical representations of prepulse signals is unclear. This study for the first time reveals that in a sound-attenuated laboratory environment, relative to the listening condition with perceptual co-location between the prepulse stimulus and a noise-masking stimulus, the perceptual separation between the two stimuli significantly enhances the group-mean PPI. More importantly, the early cortical responses (N1/P2 complex) to the prepulse stimulus are also enhanced by the perceptual separation in most listeners, and the perceptual-separation-induced enhancement of the N1 component is positively correlated with the perceptual-separation-induced PPI enhancement. Thus, the perceptual separation enhances PPI through facilitating selective attention to the prepulse, leading to an enhancement of the early cortical representation of the prepulse signal in temporal auditory cortical fields.

Ethylene has long been used to promote flowering in pineapple production. Ethylene-induced flowering is dose dependent, with a critical threshold level of ethylene response factors needed to trigger flowering. The mechanism of ethylene-induced flowering is still unclear. Here, we integrated isoform sequencing (iso-seq), Illumina short-reads sequencing and whole-genome bisulfite sequencing (WGBS) to explore the early changes of transcriptomic and DNA methylation in pineapple following high-concentration ethylene (HE) and low-concentration ethylene (LE) treatment. Iso-seq produced 122,338 transcripts, including 26,893 alternative splicing isoforms, 8,090 novel transcripts and 12,536 candidate long non-coding RNAs. The WGBS results suggested a decrease in CG methylation and increase in CHH methylation following HE treatment. The LE and HE treatments induced drastic changes in transcriptome and DNA methylome, with LE inducing the initial response to flower induction and HE inducing the subsequent response. The dose-dependent induction of FLOWERING LOCUS T-like genes (FTLs) may have contributed to dose-dependent flowering induction in pineapple by ethylene. Alterations in DNA methylation, lncRNAs and multiple genes may be involved in the regulation of FTLs. Our data provided a landscape of the transcriptome and DNA methylome and revealed a candidate network that regulates flowering time in pineapple, which may promote further studies.

Telomeric shelterin complex caps chromosome ends and plays a crucial role in telomere maintenance and protection. In the fission yeast Schizosaccharomyces pombe, shelterin is composed of telomeric single- and double-stranded DNA-binding protein subcomplexes Pot1-Tpz1 and Taz1-Rap1, which are bridged by their interacting protein Poz1. However, the structure of Poz1 and how Poz1 functions as an interaction hub in the shelterin complex remain unclear. Here we report the crystal structure of Poz1 in complex with Poz1-binding motifs of Tpz1 and Rap1. The crystal structure shows that Poz1 employs two different binding surfaces to interact with Tpz1 and Rap1. Unexpectedly, the structure also reveals that Poz1 adopts a dimeric conformation. Mutational analyses suggest that proper interactions between Tpz1, Poz1, and Rap1 in the shelterin core complex are required for telomere length homeostasis and heterochromatin structure maintenance at telomeres. Structural resemblance between Poz1 and the TRFH domains of other shelterin proteins in fission yeast and humans suggests a model for the evolution of shelterin proteins.

Telomeres are nucleoprotein complexes that play essential roles in protecting chromosome ends. Mammalian telomeres consist of repetitive DNA sequences bound by the shelterin complex. In this complex, the POT1-TPP1 heterodimer binds to single-stranded telomeric DNAs, while TRF1 and TRF2-RAP1 interact with double-stranded telomeric DNAs. TIN2, the linchpin of this complex, simultaneously interacts with TRF1, TRF2, and TPP1 to mediate the stable assembly of the shelterin complex. However, the molecular mechanism by which TIN2 interacts with these proteins to orchestrate telomere protection remains poorly understood. Here, we report the crystal structure of the N-terminal domain of TIN2 in complex with TIN2-binding motifs from TPP1 and TRF2, revealing how TIN2 interacts cooperatively with TPP1 and TRF2. Unexpectedly, TIN2 contains a telomeric repeat factor homology (TRFH)-like domain that functions as a protein-protein interaction platform. Structure-based mutagenesis analyses suggest that TIN2 plays an important role in maintaining the stable shelterin complex required for proper telomere end protection.

Elucidating the function of specific cell types in a highly complex multicellular system such as the heart often requires detailed anatomic reconstruction. We recently described a distinctive class of phenylethanolamine n-methyltransferase (Pnmt + ) cell-derived cardiomyocytes (PdCMs), a new cardiomyocyte population with a potential endocrine role. In this dataset, a 3D reconstruction was carried out to visualise the distribution of PdCMs throughout the murine heart. Rigid registration (stiff rotation and translation) was applied to properly align the fused heart slice images based on landmarks using TrakEM2, an open source plug-in in Fiji. The registered slices were then analysed and reconstructed using MATLAB (MATLAB ® . Version 8.3.0.532). The final reconstructed 3D volume was 561×866×48 pixels (corresponding to spatial resolutions of 5.8, 8.9 and 2.5 mm in the x-, y- and z-direction respectively), and visualised in Paraview. The reconstruction allows for detailed analyses of morphology, projections and cellular features of different cell types, enabling further geometrical and topological analyses. Image data can be accessed and viewed through Figshare.

Tunable metasurfaces have emerged as an efficient approach to manipulate the wave propagation. Different from previous work concentrating on electrically tunable mechanisms, here we demonstrate a magnetically tunable metasurface composed of ferrite rods and metallic foils. By tuning the thickness of ferrite rods, metasurfaces with different rod thickness gradients are obtained. The incident wave can propagate through the metasurfaces due to the extraordinary transmission. The deflection angle of the transmission wave is not only influenced by the rod thickness gradient, but also tuned by the applied magnetic field. This approach opens a way for the design of tunable metasurfaces.

Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution. We provide evidence that CBP and p300 are the major HCTs in mammalian cells. Furthermore, we have generated novel CBP/p300 mutants with deficient histone acetyltransferase but competent HCT activity. These CBP/p300 mutants can substitute the endogenous CBP/p300 to enhance transcriptional activation in the cell, which correlates with enhanced promoter crotonylation and recruitment of DPF2, a selective reader for crotonylated histones. Taken together, we have identified MOF as an evolutionarily conserved HCT and provide first cellular evidence that CBP/p300 can facilitate transcriptional activation through histone acylation other than acetylation, thus supporting an emerging role for the non-acetylation type of histone acylation in transcription and possibly other chromatin-based processes., Competing Interests: The authors declare no conflict of interest.

Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic rearrangements leading to genetic changes permissive for cancer initiation and progression. Protection of Telomere 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome stability by repressing the activation of aberrant DNA damage and repair responses at telomeres. Sporadic and familial mutations in the oligosaccharide-oligonucleotide (OB) folds of POT1 have been identified in many human cancers, but the mechanism underlying how hPOT1 mutations initiate tumorigenesis has remained unclear. Here we show that the human POT1's OB-folds are essential for the protection of newly replicated telomeres. Oncogenic mutations in hPOT1 OB-fold fail to bind to single-stranded telomeric DNA, eliciting a DNA damage response at telomeres that promote inappropriate chromosome fusions via the mutagenic alternative non-homologous end joining (A-NHEJ) pathway. hPOT1 mutations also result in telomere elongation and the formation of transplantable hematopoietic malignancies. Strikingly, conditional deletion of both mPot1a and p53 in mouse mammary epithelium resulted in development of highly invasive breast carcinomas and the formation of whole chromosomes containing massive arrays of telomeric fusions indicative of multiple breakage-fusion-bridge cycles. Our results reveal that hPOT1 OB-folds are required to protect and prevent newly replicated telomeres from engaging in A-NHEJ mediated fusions that would otherwise promote genome instability to fuel tumorigenesis.

Transposons are generally kept silent by epigenetic mechanisms including DNA methylation. Here, we identified a pair of Harbinger transposon-derived proteins (HDPs), HDP1 and HDP2, as anti-silencing factors in Arabidopsis. hdp1 and hdp2 mutants displayed an enhanced silencing of transgenes and some transposons. Phylogenetic analyses revealed that HDP1 and HDP2 were co-domesticated from the Harbinger transposon-encoded transposase and DNA-binding protein, respectively. HDP1 interacts with HDP2 in the nucleus, analogous to their transposon counterparts. Moreover, HDP1 and HDP2 are associated with IDM1, IDM2, IDM3 and MBD7 that constitute a histone acetyltransferase complex functioning in DNA demethylation. HDP2 and the methyl-DNA-binding protein MBD7 share a large set of common genomic binding sites, indicating that they jointly determine the target specificity of the histone acetyltransferase complex. Thus, our data revealed that HDP1 and HDP2 constitute a functional module that has been recruited to a histone acetyltransferase complex to prevent DNA hypermethylation and epigenetic silencing.