The epidemiological characteristics of pediatric head injury in Hangzhou, China: a retrospective study based on cranial CT examinations.

PRIMARY OBJECTIVE: This study aims to create a pediatric head injury database based on cranial CT examinations and explore their epidemiologic characteristics. METHODS: Data related to cranial CT examinations of pediatric head injuries from March 2014 to March 2021 were collected at outpatient and emergency department of a pediatric medical center. The causes of injury, observable post-injury symptoms, and cranial injury findings were extracted with the assistance of natural language processing techniques. RESULTS: Reviewing the data from records on 52,821 children with head injuries over a period of 7 years, the most common causes of pediatric head injury were falls (58.3%), traffic accidents (26.0%), smash/crush/strike (13.9%), violence (1.5%) and sports-related incidents (0.3%). Overall, most of those injured were boys which accounting for 62.2% of all cases. Skull fractures most commonly occur in the parietal bone (9.0%), followed by the occipital (5.2%), frontal (3.3%) and temporal bones (3.0%). Most intracranial hemorrhages occurred in epidural (5.8%), followed by subdural (5.1%), subarachnoid (0.9%), intraparenchymal (0.5%) and intraventricular (0.2%) hemorrhages. Spring and autumn showed more events than any other season. CONCLUSIONS: To the best of our knowledge, this is the largest sample of epidemiological study of head injury in the Chinese pediatric population to date.

Peptide degrader-based targeting of METTL3/14 improves immunotherapy response in cutaneous melanoma.

METTL3 has emerged as a promising therapeutic target in cancer treatment, although its oncogenic functions in melanoma development and potential for therapeutic targeting drug have not been fully explored. In this study, we define the oncogenic role of METTL3 in melanoma development and progression. Building on this insight, we examine our recently designed peptide inhibitor RM3, which targets the binding interface of METTL3/14 complex for disruption and subsequent ubiquitin-mediated proteasomal degradation via the E3 ligase STUB1. RM3 treatment reduces proliferation, migration, and invasion, and induces apoptosis in melanoma cells in vitro and in vivo. Subsequent transcriptomic analysis identified changes in immuno-related genes following RM3-mediated suppression of METTL3/14 N6-methyladenosine (m6A) methyltransferase activity, suggesting a potential for interaction with immunotherapy. A combination treatment of RM3 with anti-PD-1 antibody results in significantly higher beneficial tumor response in vivo, with a good safety profile. Collectively, these findings not only delineate the oncogenic role of METTL3 in melanoma but also showcase RM3, acting as a peptide degrader, as a novel and promising strategy for melanoma treatment.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Intraoperative Transfusion of Autologous Blood Protects from Acute Kidney Injury after Pediatric Congenital Heart Surgery.

Background: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery. And autologous blood transfusion (ABT) is an important predictor of postoperative AKI. Unlike previous studies, which mainly focused on the correlation between ABT and AKI, the current study focuses heavily on the causal relationship between them, thus providing guidance for the treatment of patients during hospitalization to reduce the occurrence of AKI. Methods: A retrospective cohort of 3386 patients extracted from the Pediatric Intensive Care database was used for statistical analysis, multifactorial analysis, and causal inference. Characteristics that were correlated with ABT and AKI were categorized as confounders, instrumental variables, and effect modifiers, and were entered into the DoWhy causal inference model to determine causality. The calculated average treatment effect (ATE) was compared with the results of the multifactorial analysis. Results: The adjusted odds ratio (OR) for ABT volume was obtained by multifactorial analysis as 0.964. The DoWhy model refute test was able to indicate a causal relationship between ABT and AKI. Any ABT reduces AKI about 15.3%-18.8% by different estimation methods. The ATE regarding the amount of ABT was -0.0088, suggesting that every 1 mL/kg of ABT reduced the risk of AKI by 0.88%. Conclusions: Intraoperative transfusion of autologous blood can have a protective effect against postoperative AKI.

Single-cell transcriptome analyses reveal cellular and molecular responses to low nitrogen in burley tobacco leaves.

Tobacco (Nicotiana tabacum) is cultivated and consumed worldwide. It requires great amounts of nitrogen (N) to achieve the best yield and quality. With a view to sustainable and environmentally friendly agriculture, developing new genotypes with high productivity under low N conditions is an important approach. It is unclear how genes in tobacco are expressed at the cellular level and the precise mechanisms by which cells respond to environmental stress, especially in the case of low N. Here, we characterized the transcriptomes in tobacco leaves grown in normal and low-N conditions by performing scRNA-seq. We identified 10 cell types with 17 transcriptionally distinct cell clusters with the assistance of marker genes and constructed the first single-cell atlas of tobacco leaves. Distinct gene expression patterns of cell clusters were observed under low-N conditions, and the mesophyll cells were the most important responsive cell type and displayed heterogene responses among its three subtypes. Pseudo-time trajectory analysis revealed low-N stress decelerates the differentiation towards mesophyll cells. In combination with scRNA-seq, WGCNA, and bulk RNA-seq results, we found that genes involved in porphyrin metabolism, nitrogen metabolism, carbon fixation, photosynthesis, and photosynthesis-antenna pathway play an essential role in response to low N. Moreover, we identified COL16, GATA24, MYB73, and GLK1 as key TFs in the regulation of N-responsive genes. Collectively, our findings are the first observation of the cellular and molecular responses of tobacco leaves under low N stress and lay the cornerstone for future tobacco scRNA-seq investigations.

Analysis of spatial and temporal changes in vegetation cover and its drivers in the Aksu River Basin, China.

Exploring vegetation dynamics in arid areas and their responses to different natural and anthropogenic factors is critical for understanding ecosystems. Based on the monthly MOD13Q1 (250 m) remote sensing data from 2000 to 2019, this study analyzed spatio-temporal changes in vegetation cover in the Aksu River Basin and predicted future change trends using one-dimensional linear regression, the Mann-Kendall test, and the Hurst index. Quantitative assessment of the magnitude of anthropogenic and natural drivers was performed using the Geodetector model. Eleven natural and anthropogenic factors were quantified and analyzed within five time periods. The influence of the driving factors on the changes in the normalized difference vegetation index (NDVI) in each period was calculated and analyzed. Four main results were found. (1) The overall vegetation cover in the region significantly grew from 2000 to 2019. The vegetation cover changes were dominated by expected future improvements, with a Hurst index average of 0.45. (2) Land use type, soil moisture, surface temperature, and potential vapor dispersion were the main drivers of NDVI changes, with annual average q-values above 0.2. (3) The driving effect of two-factor interactions was significantly greater than that of single factors, especially land use type interacts with other factors to a greater extent on vegetation cover. (4) The magnitude of the interaction between soil moisture and potential vapor dispersion and the magnitude of the interaction between anthropogenic factors and other factors showed an obvious increasing trend. Current soil moisture and human activities had a positive influence on the growth of vegetation in the area. The findings of this study are important for ecological monitoring and security as well as land desertification control.

The role of liquid-liquid phase separation in defining cancer EMT.

Cancer EMT is a pivotal process that drives carcinogenesis, metastasis, and cancer recurrence, with its initiation and regulation intricately governed by biochemical pathways in a precise spatiotemporal manner. Recently, the membrane-less biomolecular condensates formed via liquid-liquid phase separation (LLPS) have emerged as a universal mechanism underlying the spatiotemporal collaboration of biological activities in cancer EMT. In this review, we first elucidate the current understanding of LLPS formation and its cellular functions, followed by an overview of valuable tools for investigating LLPS. Secondly, we examine in detail the LLPS-mediated biological processes crucial for the initiation and regulation of cancer EMT. Lastly, we address current challenges in advancing LLPS research and explore the potential modulation of LLPS using therapeutic agents.

Biomimetic Design of a New Semi-Rigid Spatial Mesh Antenna Reflector.

The reflective surface accuracy (RSA) of traditional space mesh antennas typically ranges from 0.2 to 6 mmRMS. To improve the RSA, an active control scheme can be employed, although it presents challenges in determining the installation position of the actuator. In this study, we propose a novel design for a semi-rigid cable mesh that combines rigid members and a flexible woven mesh, drawing inspiration from both rigid ribbed antennas and biomimicry. Initially, we investigate the planar mesh topology of spider webs and determine the bionic cable surface's mesh topology based on the existing hexagonal meshing method, with RSA serving as the evaluation criterion. Subsequently, through motion simulations and careful observation, we establish the offset angle as the key design parameter for the bionic mesh and complete the design of the bionic cable mesh accordingly. Finally, by analyzing the impact of the node quantity on RSA, we determine a layout scheme for the flexible woven mesh with a variable number of nodes, ultimately settling for 26 nodes. Our results demonstrate that the inclusion of numerous rigid components on the bionic cable mesh surface offers viable installation positions for the actuator of the space mesh antenna. The reflector accuracy achieved is 0.196 mmRMS, slightly surpassing the lower limit of reflector accuracy observed in most traditional space-space mesh antennas. This design presents a fresh research perspective on combining active control schemes with reflective surfaces, offering the potential to enhance the RSA of traditional rigid rib antennas to a certain extent.

Eco-friendly bacterial cellulose/MXene aerogel with excellent photothermal and electrothermal conversion capabilities for efficient separation of crude oil/seawater mixture.

Developing novel absorbent materials targeting high-efficiency, low-energy-consumption, and environmental-friendly oil spill cleanup is still a global issue. Porous absorbents endowed with self-heating function are an attractive option because of that they are able to in-situ heat crude oil and dramatically reduce oil viscosity for efficient remediation. Herein, we facilely prepared an eco-friendly multifunctional bacterial cellulose/MXene aerogel (P-SBC/MXene aerogel) for rapid oil recovery. Thanks to excellent full solar spectrum absorption (average absorbance = 96.6 %), efficient photo-thermal conversion, and superior electrical conductivity (electrical resistance = 36 Ω), P-SBC/MXene aerogel exhibited outstanding photothermal and electrothermal capabilities. Its surface temperature could quickly reach 93 °C under 1.0 kW/m2 solar irradiation and 124 °C under 3.0 V voltage respectively, enabling effective heat transfer toward spilled oil. The produced heat significantly decreased crude oil viscosity, allowing P-SBC/MXene aerogel to rapidly absorb oil. By combining solar heating and Joule heating, P-SBC/MXene aerogel connected to a pump-assisted absorption device was capable of achieving all-weather crude oil removal from seawater (crude oil flux = 630 kg m-2 h-1). More notably, P-SBC/MXene aerogel showed splendid outdoor crude oil separation performance. Based on remarkable crude oil/seawater separation ability, the versatile aerogel provides a promising way to deal with large-area oil spills.

Whole-Genome Resequencing Reveals Genetic Diversity and Growth Trait-Related Genes in Pinan Cattle.

The breeding of high-quality beef cattle breeds is crucial for the development of animal husbandry, and whole-genome resequencing is widely applicated in the field of molecular breeding. Advantages in growth and reproductive traits exist in Pinan cattle compared with other cattle breeds, but there is limited research on its genomic mechanism. Using whole-genome resequencing, the genetic structure and genomic selection signatures in Pinan cattle were investigated in this study. Phylogenetic, cluster, and admixture analysis results indicated that Pinan cattle have a closer genetic relationship with Kholmogory cattle and China north cattle breeds. Through a selective sweep strategy, 207 and 54 candidate genes related to growth and reproduction and immunity, respectively, were identified in the Pinan cattle population. Given the crucial role of the glutamate-cysteine ligase catalytic (GCLC) gene in muscle antioxidative defense, the high frequency of allele T of the GCLC c.429 C>T locus in the Pinan cattle population might partially contribute to the advantages of Pinan cattle in growth performance. This study laid the foundation for the genetic improvement in Chinese local beef cattle and provide background for the studies on the growth and development of Pinan cattle.

Enhanced gene transfection and induction of apoptosis in melanoma cells by branched poly(ß-amino ester)s with uniformly distributed branching units.

Melanoma, one of the most devastating forms of skin cancer, currently lacks effective clinical treatments. Delivery of functional genes to modulate specific protein expression to induce melanoma cell apoptosis could be a promising therapeutic approach. However, transfecting melanoma cells using non-viral methods, particularly with cationic polymers, presents significant challenges. In this study, we synthesized three branched poly(ß-amino ester)s (HPAEs) with evenly distributed branching units but varying space lengths through a two-step "oligomer combination" strategy. The unique topological structure enables HPAEs to condense DNA to form nano-sized polyplexes with favorable physiochemical properties. Notably, HPAEs, especially HPAE-2 with intermediate branching unit space length, demonstrated significantly higher gene transfection efficiency than the leading commercial gene transfection reagent, jetPRIME, in human melanoma cells. Furthermore, HPAE-2 efficiently delivered the Bax-encoding plasmid into melanoma cells, leading to a pronounced pro-apoptotic effect without causing noticeable cytotoxicity. This study establishes a potent non-viral platform for gene transfection of melanoma cells by harnessing the distribution of branching units, paving the way for potential clinical applications of gene therapy in melanoma treatment.

Genomic insights into the clonal reproductive Opuntia cochenillifera: mitochondrial and chloroplast genomes of the cochineal cactus for enhanced understanding of structural dynamics and evolutionary implications.

Background: The cochineal cactus (Opuntia cochenillifera), notable for its substantial agricultural and industrial applications, predominantly undergoes clonal reproduction, which presents significant challenges in breeding and germplasm innovation. Recent developments in mitochondrial genome engineering offer promising avenues for introducing heritable mutations, potentially facilitating selective sexual reproduction through the creation of cytoplasmic male sterile genotypes. However, the lack of comprehensive mitochondrial genome information for Opuntia species hinders these efforts. Here, we intended to sequence and characterize its mitochondrial genome to maximize the potential of its genomes for evolutionary studies, molecular breeding, and molecular marker developments. Results: We sequenced the total DNA of the O. cochenillifera using DNBSEQ and Nanopore platforms. The mitochondrial genome was then assembled using a hybrid assembly strategy using Unicycler software. We found that the mitochondrial genome of O. cochenillifera has a length of 1,156,235 bp, a GC content of 43.06%, and contains 54 unique protein-coding genes and 346 simple repeats. Comparative genomic analysis revealed 48 homologous fragments shared between mitochondrial and chloroplast genomes, with a total length of 47,935 bp. Additionally, the comparison of mitochondrial genomes from four Cactaceae species highlighted their dynamic nature and frequent mitogenomic reorganizations. Conclusion: Our study provides a new perspective on the evolution of the organelle genome and its potential application in genetic breeding. These findings offer valuable insights into the mitochondrial genetics of Cactaceae, potentially facilitating future research and breeding programs aimed at enhancing the genetic diversity and adaptability of O. cochenillifera by leveraging its unique mitochondrial genome characteristics.

Deciphering the Plastomic Code of Chinese Hog-Peanut (Amphicarpaea edgeworthii Benth., Leguminosae): Comparative Genomics and Evolutionary Insights within the Phaseoleae Tribe.

The classification and phylogenetic relationships within the Phaseoleae tribe (Leguminosae) have consistently posed challenges to botanists. This study addresses these taxonomic intricacies, with a specific focus on the Glycininae subtribe, by conducting a comprehensive analysis of the highly conserved plastome in Amphicarpaea edgeworthii Benth., a critical species within this subtribe. Through meticulous genomic sequencing, we identified a plastome size of 148,650 bp, composed of 128 genes, including 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Comparative genomic analysis across seven Glycininae species illuminated a universally conserved circular and quadripartite structure, with nine genes exhibiting notable nucleotide diversity, signifying a remarkable genomic variability. Phylogenetic reconstruction of 35 Phaseoleae species underscores the affinity of Amphicarpaea with Glycine, placing Apios as a sister lineage to all other Phaseoleae species, excluding Clitorinae and Diocleinae subtribes. Intriguingly, Apios, Butea, Erythrina, and Spatholobus, traditionally clumped together in the Erythrininae subtribe, display paraphyletic divergence, thereby contesting their taxonomic coherence. The pronounced structural differences in the quadripartite boundary genes among taxa with unresolved subtribal affiliations demand a reevaluation of Erythrininae's taxonomic classification, potentially refining the phylogenetic contours of the tribe.

Multifunctional Hydrogel of Recombinant Humanized Collagen Loaded with MSCs and MnO2 Accelerates Chronic Diabetic Wound Healing.

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.

Mutant p53 achieves function by regulating EGR1 to induce epithelial mesenchymal transition.

The epithelial-mesenchymal transition (EMT) plays a crucial role in lung cancer metastasis, rendering it a promising therapeutic target. Research has shown that non-small cell lung cancer (NSCLC) with p53 mutations exhibits an increased tendency for cancer metastasis. However, the exact contribution of the p53-R273H mutation to tumor metastasis remains uncertain in the current literature. Our study established the H1299-p53-R273H cell model successfully by transfecting the p53-R273H plasmid into H1299 cells. We observed that p53-R273H promotes cell proliferation, migration, invasion, and EMT through CCK-8, wound healing, transwell, western blot and immunofluorescence assays. Notably, the expression of EGR1 was increased in H1299-p53-R273H cells. Knocking out EGR1 in these cells hindered the progression of EMT. ChIP-PCR experiments revealed that p53-R273H binds to the EGR1 promoter sequence, thereby regulating its expression. These findings suggest that p53-R273H triggers EMT by activating EGR1, thereby offering a potential therapeutic approach for lung cancer treatment.

Salvia guidongensis sp. nov.: unraveling a critical evolutionary link in East Asian Salvia from Central China integrating morphology, phylogeny, and plastid genomics.

Introduction: Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus. Methods: Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia. The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics. Results: The newly discovered species, Salvia guidongensis, exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria, S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia, suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis, comparing them with those of closely related species. Discussion: The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Quantitative microbiome profiling reveals the developmental trajectory of the chicken gut microbiota and its connection to host metabolism.

Revealing the assembly and succession of the chicken gut microbiota is critical for a better understanding of its role in chicken physiology and metabolism. However, few studies have examined dynamic changes of absolute chicken gut microbes using the quantitative microbiome profiling (QMP) method. Here, we revealed the developmental trajectory of the broiler chicken gut bacteriome and mycobiome by combining high-throughput sequencing with a microbial load quantification assay. We showed that chicken gut microbiota abundance and diversity reached a plateau at 7 days posthatch (DPH), forming segment-specific community types after 1 DPH. The bacteriome was more impacted by deterministic processes, and the mycobiome was more affected by stochastic processes. We also observed stage-specific microbes in different gut segments, and three microbial occurrence patterns including "colonization," "disappearance," and "core" were defined. The microbial co-occurrence networks were very different among gut segments, with more positive associations than negative associations. Furthermore, we provided links between the absolute changes in chicken gut microbiota and their serum metabolite variations. Time-course untargeted metabolomics revealed six metabolite clusters with different changing patterns of abundance. The foregut microbiota had more connections with chicken serum metabolites, and the gut microbes were closely related to chicken lipid and amino acid metabolism. The present study provided a full landscape of chicken gut microbiota development in a quantitative manner, and the associations between gut microbes and chicken serum metabolites further highlight the impact of gut microbiota in chicken growth and development.