A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

HSP70A promotes the photosynthetic activity of marine diatom Phaeodactylum tricornutum under high temperature.

With global climate change, the high-temperature environment has severely impacted the community structure and phenotype of marine diatoms. Phaeodactylum tricornutum, a model species of marine diatom, is sensitive to high temperature, which grow slowly under high temperature. However, the regulatory mechanism of P. tricornutum in response to high-temperature is still unclear. In this study, we found that the expression level of the HSP70A in the wild type (WT) increased 28 times when exposed to high temperature (26°C) for 1 h, indicating that HSP70A plays a role in high temperature in P. tricornutum. Furthermore, overexpression and interference of HSP70A have great impact on the exponential growth phase of P. tricornutum under 26°C. Moreover, the results of Co-immunoprecipitation (Co-IP) suggested that HSP70A potentially involved in the correct folding of the photosynthetic system-related proteins (D1/D2), preventing aggregation. The photosynthetic activity results demonstrated that overexpression of HSP70A improves non-photochemical quenching (NPQ) activity under high-temperature stress. These results reveal that HSP70A regulates the photosynthetic activity of P. tricornutum under high temperatures. This study not only helps us to understand the photosynthetic activity of marine diatoms to high temperature but also provides a molecular mechanism for HSP70A in P. tricornutum under high-temperature stress.

Genetic basis of maize stalk strength decoded via linkage and association mapping.

Stalk lodging is a severe problem that limits maize production worldwide, although little attention has been given to its genetic basis. Here we measured rind penetrometer resistance (RPR), an effective index for stalk lodging, in a multi-parent population of 1948 recombinant inbred lines (RILs) and an association population of 508 inbred lines (AMP508). Linkage and association mapping identified 53 and 29 single quantitative trait loci (QTLs) and 50 and 19 pairs of epistatic interactions for RPR in the multi-parent population and AMP508 population, respectively. Phenotypic variation explained by all identified epistatic QTLs (up to ~5%) was much less than that explained by all single additive QTLs (up to ~33% in the multi-parent population and ~ 60% in the AMP508 population). Among all detected QTLs, only eight single QTLs explained >10% of phenotypic variation in single RIL populations. Alleles that increased RPR were enriched in tropical/subtropical (TST) groups from the AMP508 population. Based on genome-wide association studies in both populations, we identified 137 candidate genes affecting RPR, which were assigned to multiple biological processes, such as the biosynthesis of cell wall components. Sixty-six candidate genes were cross-validated by multiple methods or populations. Most importantly, 23 candidate genes were upregulated or downregulated in high-RPR lines relative to low-RPR lines, supporting the associations between candidate genes and RPR. These findings reveal the complex nature of the genetic basis underlying RPR and provide loci or candidate genes for developing elite varieties that are resistant to stalk lodging via molecular breeding.

Rectifying METTL4-Mediated N6-Methyladenine Excess in Mitochondrial DNA Alleviates Heart Failure.

BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.

Cognitive and neural mechanisms of voluntary versus forced language switching in Chinese-English bilinguals: an fMRI study.

The ecological validity of bilingual code-switching has garnered increasing attention in recent years. Contrary to traditional studies that have focused on forced language switching, emerging theories posit that voluntary switching may not incur such a cost. To test these claims and understand differences between forced and voluntary switching, the present study conducted a systematic comparison through both behavioral and neural perspectives. Utilizing fMRI alongside picture-naming tasks, our findings diverge from prior work. Voluntary language switching not only demonstrated switching costs at the behavioral level but also significantly activated brain regions associated with inhibitory control. Direct comparisons of voluntary and forced language switching revealed no significant behavioral differences in switching costs, and both shared several common brain regions that were activated. On the other hand, a nuanced difference between the two types of language switching was revealed by whole-brain analysis: voluntary switching engaged fewer language control regions than forced switching. These findings offer a comprehensive view of the neural and behavioral dynamics involved in bilingual language switching, challenging prior claims that voluntary switching imposes no behavioral or neural costs, and thus providing behavioral and neuroimaging evidence for the involvement of inhibitory control in voluntary language switching.

Theta Signal Transfer from Parietal to Prefrontal Cortex Ignites Conscious Awareness of Implicit Knowledge during Sequence Learning.

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.

HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner.

Glioma is the most common malignant tumor in the central nervous system, and it is crucial to uncover the factors that influence prognosis. In this study, we utilized Mfuzz to identify a gene set that showed a negative correlation with overall survival in patients with glioma. Gene Ontology (GO) enrichment analyses were then undertaken to gain insights into the functional characteristics and pathways associated with these genes. The expression distribution of Hyaluronan Synthase 2 (HAS2) was explored across multiple datasets, revealing its expression patterns. In vitro and in vivo experiments were carried out through gene knockdown and overexpression to validate the functionality of HAS2. Potential upstream transcription factors of HAS2 were predicted using transcriptional regulatory databases, and these predictions were experimentally validated using ChIP-PCR and dual-luciferase reporter gene assays. The results showed that elevated expression of HAS2 in glioma indicates poor prognosis. HAS2 was found to play a role in activating an antiferroptosis pathway in glioma cells. Inhibiting HAS2 significantly increased cellular sensitivity to ferroptosis-inducing agents. Finally, we determined that the oncogenic effect of HAS2 is mediated by the key receptor of the WNT pathway, FZD7.

Designing Compatible Ceramic/Polymer Composite Solid-State Electrolyte for Stable Silicon Nanosheet Anodes.

The commercialization of silicon anode for lithium-ion batteries has been hindered by severe structure fracture and continuous interfacial reaction against liquid electrolytes, which can be mitigated by solid-state electrolytes. However, rigid ceramic electrolyte suffers from large electrolyte/electrode interfacial resistance, and polymer electrolyte undergoes poor ionic conductivity, both of which are worsened by volume expansion of silicon. Herein, by dispersing Li1.3Al0.3Ti1.7(PO4)3 (LATP) into poly(vinylidene fluoride)-hexafluoropropylene (PVDF-HFP) and poly(ethylene oxide) (PEO) matrix, the PVDF-HFP/PEO/LATP (PHP-L) solid-state electrolyte with high ionic conductivity (1.40 × 10-3 S cm-1), high tensile strength and flexibility is designed, achieving brilliant compatibility with silicon nanosheets. The chemical interactions between PVDF-HFP and PEO, LATP increase amorphous degree of polymer, accelerating Li+ transfer. Good flexibility of the PHP-L contributes to adaptive structure variation of electrolyte with silicon expansion/shrinkage, ensuring swift interfacial ions transfer. Moreover, the solid membrane with high tensile limits electrode structural degradation and eliminates continuous interfacial growth to form stable 2D solid electrolyte interface (SEI) film, achieving superior cyclic performance to liquid electrolytes. The Si//PHP-L15//LiFePO4 solid-state full-cell exhibits stable lithium storage with 81% capacity retention after 100 cycles. This work demonstrates the effectiveness of composite solid electrolyte in addressing fundamental interfacial and performance challenges of silicon anodes.

Insights into spinach domestication from genome sequences of two wild spinach progenitors, Spinacia turkestanica and Spinacia tetrandra.

Cultivated spinach (Spinacia oleracea) is a dioecious species. We report high-quality genome sequences for its two closest wild relatives, Spinacia turkestanica and Spinacia tetrandra, which are also dioecious, and are used to study the genetics of spinach domestication. Using a combination of genomic approaches, we assembled genomes of both these species and analyzed them in comparison with the previously assembled S. oleracea genome. These species diverged c. 6.3 million years ago (Ma), while cultivated spinach split from S. turkestanica 0.8 Ma. In all three species, all six chromosomes include very large gene-poor, repeat-rich regions, which, in S. oleracea, are pericentromeric regions with very low recombination rates in both male and female genetic maps. We describe population genomic evidence that the similar regions in the wild species also recombine rarely. We characterized 282 structural variants (SVs) that have been selected during domestication. These regions include genes associated with leaf margin type and flowering time. We also describe evidence that the downy mildew resistance loci of cultivated spinach are derived from introgression from both wild spinach species. Collectively, this study reveals the genome architecture of spinach assemblies and highlights the importance of SVs during the domestication of cultivated spinach.

Evolution of the spinach sex-linked region within a rarely recombining pericentromeric region.

Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by sequencing homozygous XX females and YY males. The long arm of 185-Mb chromosome 4 carries a 13-Mb X-linked region (XLR) and 24.1-Mb Y-linked region (YLR), of which 10 Mb is Y specific. We describe evidence that this reflects insertions of autosomal sequences creating a "Y duplication region" or "YDR" whose presence probably directly reduces genetic recombination in the immediately flanking regions, although both the X and Y sex-linked regions are within a large pericentromeric region of chromosome 4 that recombines rarely in meiosis of both sexes. Sequence divergence estimates using synonymous sites indicate that YDR genes started diverging from their likely autosomal progenitors about 3 MYA, around the time when the flanking YLR stopped recombining with the XLR. These flanking regions have a higher density of repetitive sequences in the YY than the XX assembly and include slightly more pseudogenes compared with the XLR, and the YLR has lost about 11% of the ancestral genes, suggesting some degeneration. Insertion of a male-determining factor would have caused Y linkage across the entire pericentromeric region, creating physically small, highly recombining, terminal pseudoautosomal regions. These findings provide a broader understanding of the origin of sex chromosomes in spinach.

Target recycle initiated entropy driven assembly strategy for sensitive, enzyme-free, and portable miRNA detection.

MicroRNA (miRNA) is a pivotal biomarker in the diagnosis of various cancers, including bladder cancer (BCa). Despite their significance, the low abundance of miRNA presents a substantial challenge for sensitive and reliable detection. We introduce an innovative, highly sensitive assay for miRNA expression quantification that is both enzyme-free and portable. This method leverages the synergy of target recycling and entropy-driven assembly (EDA) for enhanced sensitivity and specificity. The proposed method possesses several advantages, including i) dual signal amplification through target recycling and EDA, which significantly boosts sensitivity with a lower limit of detection of 2.54 fM; ii) elimination of enzyme requirements, resulting in a cost-effective and stable signal amplification process; and iii) utilization of a personal glucose meter (PGM) for signal recording, rendering the method portable and adaptable to diverse settings. In summary, this PGM-based approach holds promising potential for clinical molecular diagnostics, offering a practical and efficient solution for miRNA analysis in cancer detection.

Programmable living assembly of materials by bacterial adhesion.

The field of engineered living materials aims to construct functional materials with desirable properties of natural living systems. A recent study demonstrated the programmed self-assembly of bacterial populations by engineered adhesion. Here we use this strategy to engineer self-healing living materials with versatile functions. Bacteria displaying outer membrane-anchored nanobody-antigen pairs are cultured separately and, when mixed, adhere to each other to enable processing into functional materials, which we term living assembled material by bacterial adhesion (LAMBA). LAMBA is programmable and can be functionalized with extracellular moieties up to 545 amino acids. Notably, the adhesion between nanobody-antigen pairs in LAMBA leads to fast recovery under stretching or bending. By exploiting this feature, we fabricated wearable LAMBA sensors that can detect bioelectrical or biomechanical signals. Our work establishes a scalable approach to produce genetically editable and self-healable living functional materials that can be applied in biomanufacturing, bioremediation and soft bioelectronics assembly.

Genomic and biological characteristics of a novel leafhopper-transmitted marafivirus infecting Triticum aestivum.

Here, we report a novel wheat-infecting marafivirus, tentatively named "Triticum aestivum marafivirus" (TaMRV). The full-length genome sequence of TaMRV comprises 6,437 nucleotides, excluding the poly(A) tail. Pairwise sequence comparisons and phylogenetic analysis revealed that TaMRV may represent a novel species within the genus Marafivirus in the family Tymoviridae. We also observed a mass of isometric particles with a diameter of about 30 nm in ultrathin sections of infected wheat leaf tissue. In addition, the leafhopper Psammotettix alienus was identified as a vector for this virus. This is the first report of the occurrence of a wheat-infecting marafivirus.

Different computational relations in language are captured by distinct brain systems.

A critical way for humans to acquire information is through language, yet whether and how language experience drives specific neural semantic representations is still poorly understood. We considered statistical properties captured by 3 different computational principles of language (simple co-occurrence, network-(graph)-topological relations, and neural-network-vector-embedding relations) and tested the extent to which they can explain the neural patterns of semantic representations, measured by 2 functional magnetic resonance imaging experiments that shared common semantic processes. Distinct graph-topological word relations, and not simple co-occurrence or neural-network-vector-embedding relations, had unique explanatory power for the neural patterns in the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were relatively specific to language: they were not explained by sensory-motor similarities and the same computational relations of visual objects (based on visual image database) showed effects in the visual cortex in the picture naming experiment. That is, different topological properties within language and the same topological computations (common-neighbors) for language and visual inputs are captured by different brain regions. These findings reveal the specific neural semantic representations along graph-topological properties of language, highlighting the information type-specific and statistical property-specific manner of semantic representations in the human brain.

Maternal Diabetes and Risk of Hypospadias: A Systemic Review and Meta-Analysis.

INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.

Genome-Wide Identification and Characterization of MYB Gene Family and Analysis of Its Sex-Biased Expression Pattern in Spinacia oleracea L.

The members of the myeloblastosis (MYB) family of transcription factors (TFs) participate in a variety of biological regulatory processes in plants, such as circadian rhythm, metabolism, and flower development. However, the characterization of MYB genes across the genomes of spinach Spinacia oleracea L. has not been reported. Here, we identified 140 MYB genes in spinach and described their characteristics using bioinformatics approaches. Among the MYB genes, 54 were 1R-MYB, 80 were 2R-MYB, 5 were 3R-MYB, and 1 was 4R-MYB. Almost all MYB genes were located in the 0-30 Mb region of autosomes; however, the 20 MYB genes were enriched at both ends of the sex chromosome (chromosome 4). Based on phylogeny, conserved motifs, and the structure of genes, 2R-MYB exhibited higher conservation relative to 1R-MYB genes. Tandem duplication and collinearity of spinach MYB genes drive their evolution, enabling the functional diversification of spinach genes. Subcellular localization prediction indicated that spinach MYB genes were mainly located in the nucleus. Cis-acting element analysis confirmed that MYB genes were involved in various processes of spinach growth and development, such as circadian rhythm, cell differentiation, and reproduction through hormone synthesis. Furthermore, through the transcriptome data analysis of male and female flower organs at five different periods, ten candidate genes showed biased expression in spinach males, suggesting that these genes might be related to the development of spinach anthers. Collectively, this study provides useful information for further investigating the function of MYB TFs and novel insights into the regulation of sex determination in spinach.

MR-based spatiotemporal anisotropic atrophy evaluation of hippocampus in Alzheimer's disease progression by multiscale skeletal representation.

Increasing evidence has shown a higher sensitivity of Alzheimer's disease (AD) progression by local hippocampal atrophy rather than the whole volume. However, existing morphological methods based on subfield-volume or surface in imaging studies are not capable to describe the comprehensive process of hippocampal atrophy as sensitive as histological findings. To map histological distinctive measurements onto medical magnetic resonance (MR) images, we propose a multiscale skeletal representation (m-s-rep) to quantify focal hippocampal atrophy during AD progression in longitudinal cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The m-s-rep captures large-to-small-scale hippocampal morphology by spoke interpolation over label projection on skeletal models. To enhance morphological correspondence within subjects, we align the longitudinal m-s-reps by surface-based transformations from baseline to subsequent timepoints. Cross-sectional and longitudinal measurements derived from m-s-rep are statistically analyzed to comprehensively evaluate the bilateral hippocampal atrophy. Our findings reveal that during the early AD progression, atrophy primarily affects the lateral-medial extent of the hippocampus, with a difference of 1.8 mm in lateral-medial width in 2 years preceding conversion (p < .001), and the medial head exhibits a maximum difference of 3.05%/year in local atrophy rate (p = .011) compared to controls. Moreover, progressive mild cognitive impairment (pMCI) exhibits more severe and widespread atrophy in the head and body compared to stable mild cognitive impairment (sMCI), with a maximum difference of 1.21 mm in thickness in the medial head 1 year preceding conversion (p = .012). In summary, our proposed method can quantitatively measure the hippocampal morphological changes on 3T MR images, potentially assisting the pre-diagnosis and prognosis of AD.

Mass Loading-Independent Lithium Storage of Transitional Metal Compounds Achieved by Multi-Dimensional Synergistic Nanoarchitecture.

Nanostructured transitional metal compounds (TMCs) have demonstrated extraordinary promise for high-efficient and rapid lithium storage. However, good performance is usually limited to electrodes with low mass loading (≤1.0 mg cm-2 ) and is difficult to realize at higher mass loading due to increased electrons/ions transport limitations in the thicker electrode. Herein, the multi-dimensional synergistic nanoarchitecture design of graphene-wrapped MnO@carbon microcapsules (capsule-like MnO@C-G) is reported, which demonstrates impressive mass loading-independent lithium storage properties. Highly porous MnO nanoclusters assembled by 0D nanocrystals facilitate sufficient electrolyte infiltration and shorten the solid-state ions transport path. 1D carbon shell, 2D graphene, and 3D continuous network with tight interconnection accelerate electrons transport inside the thick electrode. The capsule-like MnO@C-G delivers ultrahigh gravimetric capacity retention of 91.0% as the mass loading increases 4.3 times, while the areal capacities increase linearly with the mass loading at various current densities. Specifically, the capsule-like MnO@C electrode delivers a remarkable areal capacity of 2.0 mAh cm-2 at a mass loading of 3.0 mg cm-2 . Moreover, the capsule-like MnO@C also demonstrates excellent performance in full battery applications. This study demonstrates the effectiveness of multi-dimensional synergistic nanoarchitecture in achieving mass loading-independent performance, which can be extended to other TMCs for electrochemical energy storage.

The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma.

BACKGROUND: Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression. METHODS: Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2. CONCLUSION: Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.