Cup-like nuclei in adult B-cell acute lymphoblastic leukemia with the translocation (4;11)(q21;q23).

Cuplike Nuclei(CLN) cells, particularly rare in Acute Lymphoblastic Leukemia(ALL), have been documented in only few cases to date. A recent study has revealed a correlation between CLN and IKZF1 deletions in pediatric B-ALL. This study introduces a case of CLN in adult B-ALL with a translocation (4;11)(q21;q23), while discussing the current relevant literature on the subject. Through this examination, several unique characteristics of CLN cells in both ALL and Acute Myeloid Leukemia are highlighted. It is essential to accumulate further data to confirm these distinctive traits, and investigate the potential association between CLN and cytogenetic/molecular abnormalities.

Vaspin facilitates the proliferation and osteogenic differentiation of periodontal ligament stem cells.

OBJECTIVE: To investigate whether visceral adipose tissue-derived serine protease inhibitor (vaspin) can alleviate the inhibitory effect of high-glucose (HG) culture on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) and to preliminarily explore the underlying mechanisms. BACKGROUND: High glucose produces damage to the regeneration of periodontal tissue of PDLSCs. The expression level of vaspin in periodontal tissue is high in periodontitis patients and effectively reduced after initial therapy of periodontal diseases. However, the effect of vaspin on PDLSCs remains unknown. MATERIALS AND METHODS: PDLSCs were cultured in media augmented with 5.5 or 25.0 mM concentrations of glucose to elucidate the impact and mechanism of vaspin on PDLSCs under high glucose in vitro. Proliferation was measured by Cell Counting Kit-8 (CCK8) assay. Osteogenesis of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, and Alizarin Red staining. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) were used to investigate the osteo-specific markers. Then, the molecular impact of vaspin in the presence/absence of HG on PDLSCs physiology was determined with TGF-ß1/Smad signaling pathway as the main focus. RESULTS: It was revealed that the proliferation and osteogenic differentiation (OD) of PDLSCs under HG was reduced, and by adding vaspin the anti-osteogenic impact of HG was relieved. Moreover, vaspin enhanced TGF-ß1/Smad signaling pathway activity. Pretreatment with TGF-ß1 inhibitor blocked vaspin-triggered TGF-ß1/Smad signal activation and minimized the vaspin-induced protective effect against HG-inhibited growth and OD. CONCLUSIONS: In summary, vaspin observably reduces HG-mediated inhibition of PDLSCs OD by modulating the TGF-ß1/Smad signaling pathway. Vaspin may be a potential therapeutic for periodontal tissue regeneration in diabetic patients.

Body size as a metric for the affordable world.

The physical body of an organism serves as a vital interface for interactions with its environment. Here, we investigated the impact of human body size on the perception of action possibilities (affordances) offered by the environment. We found that the body size delineated a distinct boundary on affordances, dividing objects of continuous real-world sizes into two discrete categories with each affording distinct action sets. Additionally, the boundary shifted with imagined body sizes, suggesting a causal link between body size and affordance perception. Intriguingly, ChatGPT, a large language model lacking physical embodiment, exhibited a modest yet comparable affordance boundary at the scale of human body size, suggesting the boundary is not exclusively derived from organism-environment interactions. A subsequent fMRI experiment offered preliminary evidence of affordance processing exclusively for objects within the body size range, but not for those beyond. This suggests that only objects capable of being manipulated are the objects capable of offering affordance in the eyes of an organism. In summary, our study suggests a novel definition of object-ness in an affordance-based context, advocating the concept of embodied cognition in understanding the emergence of intelligence constrained by an organism's physical attributes.

Sequencing of N6-methyl-deoxyadenosine at single-base resolution across the mammalian genome.

Although DNA N6-methyl-deoxyadenosine (6mA) is abundant in bacteria and protists, its presence and function in mammalian genomes have been less clear. We present Direct-Read 6mA sequencing (DR-6mA-seq), an antibody-independent method, to measure 6mA at base resolution. DR-6mA-seq employs a unique mutation-based strategy to reveal 6mA sites as misincorporation signatures without any chemical or enzymatic modulation of 6mA. We validated DR-6mA-seq through the successful mapping of the well-characterized G(6mA)TC motif in the E. coli DNA. As expected, when applying DR-6mA-seq to mammalian systems, we found that genomic DNA (gDNA) 6mA abundance is generally low in most mammalian tissues and cells; however, we did observe distinct gDNA 6mA sites in mouse testis and glioblastoma cells. DR-6mA-seq provides an enabling tool to detect 6mA at single-base resolution for a comprehensive understanding of DNA 6mA in eukaryotes.

BID-seq for transcriptome-wide quantitative sequencing of mRNA pseudouridine at base resolution.

Pseudouridine (Ψ) is an abundant RNA modification that is present in and affects the functions of diverse non-coding RNA species, including rRNA, tRNA and small nuclear RNA. Ψ also exists in mammalian mRNA and probably exhibits functional roles; however, functional investigations of mRNA Ψ modifications in mammals have been hampered by the lack of a quantitative method that detects Ψ at base precision. We have recently developed bisulfite-induced deletion sequencing (BID-seq), which provides the community with a quantitative method to map RNA Ψ distribution transcriptome-wide at single-base resolution. Here, we describe an optimized BID-seq protocol for mapping Ψ distribution across cellular mRNAs, which includes fast steps in both library preparation and data analysis. This protocol generates highly reproducible results by inducing high deletion ratios at Ψ modification within diverse sequence contexts, and meanwhile displayed almost zero background deletions at unmodified uridines. When used for transcriptome-wide Ψ profiling in mouse embryonic stem cells, the current protocol uncovered 8,407 Ψ sites from as little as 10 ng of polyA+ RNA input. This optimized BID-seq workflow takes 5 days to complete and includes four main sections: RNA preparation, library construction, next-generation sequencing (NGS) and data analysis. Library construction can be completed by researchers who have basic knowledge and skills in molecular biology and genetics. In addition to the experimental protocol, we provide BID-pipe ( https://github.com/y9c/pseudoU-BIDseq ), a user-friendly data analysis pipeline for Ψ site detection and modification stoichiometry quantification, requiring only basic bioinformatic and computational skills to uncover Ψ signatures from BID-seq data.

Phase transition and lysosomal degradation of expanded CAG repeat RNA suppress global protein synthesis.

Phase transitions (PT) of biomolecules are heavily involved in neurodegenerative disorders. Almost all previous studies were focusing on the PT of misfolded proteins whereas RNA molecules containing expanded repeats such as the CAG repeats are also able to undergo PT in vitro, a process called RNA gelation. Meanwhile, the expanded CAG repeat (eCAGr) RNA forms condensates that are largely observed only in the nuclei and exhibit liquid-like properties without obvious gelation. Thus, whether eCAGr RNA gelation occurs in cells and what function it is involved in remained elusive. We recently discovered that eCAGr RNA forms solid-like RNA gels in the cytoplasm, but they are rapidly cleared by the lysosomes via an autophagy-independent but LAMP2C-depdent pathway, making their presence in the cytoplasm difficult to be observed. We further revealed that these RNA gels sequester EEF2 in the cells and thus suppress global protein synthesis. In vivo expression of eCAGr RNA alone without detectable protein expression in the mouse model led to neurodegeneration-relevant electrophysiological and behavioral phenotypes, demonstrating its possible pathogenic roles.

Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis.

RNA molecules with the expanded CAG repeat (eCAGr) may undergo sol-gel phase transitions, but the functional impact of RNA gelation is completely unknown. Here, we demonstrate that the eCAGr RNA may form cytoplasmic gel-like foci that are rapidly degraded by lysosomes. These RNA foci may significantly reduce the global protein synthesis rate, possibly by sequestering the translation elongation factor eEF2. Disrupting the eCAGr RNA gelation restored the global protein synthesis rate, whereas enhanced gelation exacerbated this phenotype. eEF2 puncta were significantly enhanced in brain slices from a knock-in mouse model and from patients with Huntington's disease, which is a CAG expansion disorder expressing eCAGr RNA. Finally, neuronal expression of the eCAGr RNA by adeno-associated virus injection caused significant behavioral deficits in mice. Our study demonstrates the existence of RNA gelation inside the cells and reveals its functional impact, providing insights into repeat expansion diseases and functional impacts of RNA phase transition.

Fundamental mechanistic insights into the catalytic reactions of Li─S redox by Co single-atom electrocatalysts via operando methods.

Lithium-sulfur batteries represent an attractive option for energy storage applications. A deeper understanding of the multistep lithium-sulfur reactions and the electrocatalytic mechanisms are required to develop advanced, high-performance batteries. We have systematically investigated the lithium-sulfur redox processes catalyzed by a cobalt single-atom electrocatalyst (Co-SAs/NC) via operando confocal Raman microscopy and x-ray absorption spectroscopy (XAS). The real-time observations, based on potentiostatic measurements, indicate that Co-SAs/NC efficiently accelerates the lithium-sulfur reduction/oxidation reactions, which display zero-order kinetics. Under galvanostatic discharge conditions, the typical stepwise mechanism of long-chain and intermediate-chain polysulfides is transformed to a concurrent pathway under electrocatalysis. In addition, operando cobalt K-edge XAS studies elucidate the potential-dependent evolution of cobalt's oxidation state and the formation of cobalt-sulfur bonds. Our work provides fundamental insights into the mechanisms of catalyzed lithium-sulfur reactions via operando methods, enabling a deeper understanding of electrocatalysis and interfacial dynamics in electrical energy storage systems.

Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing.

The Ras GTPase-activating protein SYNGAP1 plays a central role in synaptic plasticity, and de novo SYNGAP1 mutations are among the most frequent causes of autism and intellectual disability. How SYNGAP1 is regulated during development and how to treat SYNGAP1-associated haploinsufficiency remain challenging questions. Here, we characterize an alternative 3' splice site (A3SS) of SYNGAP1 that induces nonsense-mediated mRNA decay (A3SS-NMD) in mouse and human neural development. We demonstrate that PTBP1/2 directly bind to and promote SYNGAP1 A3SS inclusion. Genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates the long-term potentiation and membrane excitability deficits caused by a Syngap1 knockout allele. We further report a splice-switching oligonucleotide (SSO) that converts SYNGAP1 unproductive isoform to the functional form in human iPSC-derived neurons. This study describes the regulation and function of SYNGAP1 A3SS-NMD, the genetic rescue of heterozygous Syngap1 knockout mice, and the development of an SSO to potentially alleviate SYNGAP1-associated haploinsufficiency.

Mammalian DNA N6-methyladenosine: Challenges and new insights.

DNA N6-methyldeoxyadenosine (6mA) modification was first discovered in Bacterium coli in the 1950s. Over the next several decades, 6mA was recognized as a critical DNA modification in the genomes of prokaryotes and protists. While important in prokaryotes, less is known about the presence and functional roles of DNA 6mA in eukaryotes, particularly in mammals. Taking advantage of recent technology advances that made 6mA detection and sequencing possible, studies over the past several years have brought new insights into 6mA biology in mammals. In this perspective, we present recent progress, discuss challenges, and pose four questions for future research regarding mammalian DNA 6mA.

Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution.

Functional characterization of pseudouridine (Ψ) in mammalian mRNA has been hampered by the lack of a quantitative method that maps Ψ in the whole transcriptome. We report bisulfite-induced deletion sequencing (BID-seq), which uses a bisulfite-mediated reaction to convert pseudouridine stoichiometrically into deletion upon reverse transcription without cytosine deamination. BID-seq enables detection of abundant Ψ sites with stoichiometry information in several human cell lines and 12 different mouse tissues using 10-20 ng input RNA. We uncover consensus sequences for Ψ in mammalian mRNA and assign different 'writer' proteins to individual Ψ deposition. Our results reveal a transcript stabilization role of Ψ sites installed by TRUB1 in human cancer cells. We also detect the presence of Ψ within stop codons of mammalian mRNA and confirm the role of Ψ in promoting stop codon readthrough in vivo. BID-seq will enable future investigations of the roles of Ψ in diverse biological processes.

Understanding the lithium-sulfur battery redox reactions via operando confocal Raman microscopy.

The complex interplay and only partial understanding of the multi-step phase transitions and reaction kinetics of redox processes in lithium-sulfur batteries are the main stumbling blocks that hinder the advancement and broad deployment of this electrochemical energy storage system. To better understand these aspects, here we report operando confocal Raman microscopy measurements to investigate the reaction kinetics of Li-S redox processes and provide mechanistic insights into polysulfide generation/evolution and sulfur deposition. Operando visualization and quantification of the reactants and intermediates enabled the characterization of potential-dependent rates during Li-S redox and the linking of the electronic conductivity of the sulfur-based electrode and concentrations of polysulfides to the cell performance. We also report the visualization of the interfacial evolution and diffusion processes of different polysulfides that demonstrate stepwise discharge and parallel recharge mechanisms during cell operation. These results provide fundamental insights into the mechanisms and kinetics of Li-S redox reactions.

Oxidative Stability Matters: A Case Study of Palladium Hydride Nanosheets for Alkaline Fuel Cells.

Pd-based electrocatalysts are considered to be a promising alternative to Pt in anion-exchange membrane fuel cells (AEMFCs), although major challenges remain. Most of the Pd-based electrocatalysts developed for the sluggish oxygen reduction reaction (ORR) have been exclusively evaluated by rotating disk electrode (RDE) voltammetry at room temperature, rather than in membrane electrode assemblies (MEAs), making it challenging to apply them in practical fuel cells. We have developed a series of carbon-supported novel PdHx nanosheets (PdHx NS), which displayed outstanding ORR performance in room-temperature RDE tests. Specifically, a sample synthesized at 190 °C displayed a mass activity of 0.67 A mg-1 and a specific activity of 1.07 mA cm-2 at 0.95 V vs RHE, representing the highest reported value among Pd-based ORR electrocatalysts in alkaline media and higher than Pt-based catalysts reported in the literature. Furthermore, we employed PdHx NS and commercial Pd/C as model catalysts to systematically study the effects of temperature on their ORR activity in RDE measurements and subsequently evaluated their performance in MEA testing. Our observations indicate/demonstrate how oxidative stability affected the ORR performance of Pd-based electrocatalysts, which provided some critical insights into future ORR catalyst development for alkaline fuel cell applications.

Nonprecious transition metal nitrides as efficient oxygen reduction electrocatalysts for alkaline fuel cells.

Hydrogen fuel cells have attracted growing attention for high-performance automotive power but are hindered by the scarcity of platinum (and other precious metals) used to catalyze the sluggish oxygen reduction reaction (ORR). We report on a family of nonprecious transition metal nitrides (TMNs) as ORR electrocatalysts in alkaline medium. The air-exposed nitrides spontaneously form a several-nanometer-thick oxide shell on the conductive nitride core, serving as a highly active catalyst architecture. The most active catalyst, carbon-supported cobalt nitride (Co3N/C), exhibited a half-wave potential of 0.862 V and achieved a record-high peak power density among reported nitride cathode catalysts of 700 mW cm-2 in alkaline membrane electrode assemblies. Operando x-ray absorption spectroscopy studies revealed that Co3N/C remains stable below 1.0 V but experiences irreversible oxidation at higher potentials. This work provides a comprehensive analysis of nonprecious TMNs as ORR electrocatalysts and will help inform future design of TMNs for alkaline fuel cells and other energy applications.

Trait/Financial Information of Potential Male Mate Eliminates Mate-Choice Copying by Women: Trade-Off Between Social Information and Personal Information in Mate Selection.

Mate-choice copying occurs when people rely on the mate choices of others (social information) to inform their own mate decisions. The present study investigated women's strategic trade-off between such social learning and using the personal information of a potential mate. We conducted two experiments to investigate how mate-choice copying was affected by the personal information (e.g., trait/financial information, negative/positive valence of this information, and attractiveness) of a potential male mate in short-/long-term mate selection. The results demonstrated that when women had no trait/financial information other than photos of potential mates, they showed mate-choice copying, but when women obtained personality trait or financial situation information (no matter negative or positive) of a potential mate, their mate-choice copying disappeared; this effect was only observed for low-attractiveness and long-term potential partners. These results demonstrated human social learning strategies in mate selection through a trade-off between social information and personal information.

ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing.

Members of the mammalian AlkB family are known to mediate nucleic acid demethylation1,2. ALKBH7, a mammalian AlkB homologue, localizes in mitochondria and affects metabolism3, but its function and mechanism of action are unknown. Here we report an approach to site-specifically detect N1-methyladenosine (m1A), N3-methylcytidine (m3C), N1-methylguanosine (m1G) and N2,N2-dimethylguanosine (m22G) modifications simultaneously within all cellular RNAs, and discovered that human ALKBH7 demethylates m22G and m1A within mitochondrial Ile and Leu1 pre-tRNA regions, respectively, in nascent polycistronic mitochondrial RNA4-6. We further show that ALKBH7 regulates the processing and structural dynamics of polycistronic mitochondrial RNAs. Depletion of ALKBH7 leads to increased polycistronic mitochondrial RNA processing, reduced steady-state mitochondria-encoded tRNA levels and protein translation, and notably decreased mitochondrial activity. Thus, we identify ALKBH7 as an RNA demethylase that controls nascent mitochondrial RNA processing and mitochondrial activity.

Understanding the document bias in face matching.

Matching unfamiliar faces is a well-studied task, apparently capturing important everyday decisions such as ID checks. In typical laboratory studies, participants make same/different judgements to pairs of faces, presented in isolation and without context. However, it has recently become clear that matching faces embedded in documents (e.g., passports and driving licences) induces a bias, resulting in elevated levels of "same person" responses. While practically important, it remains unclear whether this bias arises due to expectations induced by the ID cards or interference between textual information and faces. Here, we observe the same bias when faces are embedded in blank (i.e., non-authoritative) cards carrying basic personal information, but not when the same information is presented alongside a face without the card (Experiments 1 and 2). Cards bearing unreadable text (blurred or in an unfamiliar alphabet) do not induce the bias, but those bearing arbitrary (non-biographical) words do (Experiments 3 and 4). The results suggest a complex basis for the effect, relying on multiple factors which happen to converge in photo-ID.

The constancy of the holistic processing of unfamiliar faces: Evidence from the study-test consistency effect and the within-person motion and viewpoint invariance.

It has been well documented that static face processing is holistic. Faces contain variant (e.g., motion, viewpoint) and invariant (race, sex) features. However, little research has focused on whether holistic face representations are tolerant of within-person variations. The present study thus investigated whether holistic face representations of faces are tolerant of within-person motion and viewpoint variations by manipulating study-test consistency using a complete composite paradigm. Participants were shown two faces sequentially and were asked to judge whether the faces' top halves were identical or different. The first face was a static face or a dynamic face rotated in depth at 30°, 60°, and 90°. The second face was either a different front-view static face (Experiment 1a, study-test inconsistent) or identical to the first face (Experiment 1b, study-test consistent). In Experiment 2, study-test consistency was manipulated within subjects, and inverted faces were included. Our results show that study-test consistency significantly enhanced the holistic processing of upright and inverted faces; this study-test consistency effect and holistic processing were not modulated by motion and viewpoint changes via depth rotation. Interestingly, we found holistic processing for moving study-test consistent inverted faces, but not for static inverted faces. What these results tell us about the nature of holistic face representation is discussed in depth with respect to earlier and current theories on face processing.

An Innovative Lithium Ion Battery System Based on a Cu2S Anode Material.

Cu2S is considered as one of the potential anode paradigms for advanced rechargeable batteries because of its high theoretical capacity (∼335 mAh·g-1), high and flat charge/discharge voltage plateaus (∼1.7 V vs Li+/Li), stable cycling performance, and its elemental abundance. However, many studies have shown that Cu2S exhibits a dramatic capacity fade in carbonate-based electrolytes, which has precluded its commercialization when paired with high voltage cathodes in state-of-the-art lithium ion batteries. Here, we report on a fundamental mechanistic study of the electrochemical processes of Cu2S in both ether- and carbonate-based electrolytes employing operando synchrotron X-ray methods. Based on our findings, we developed a Cu2S/C composite material that suppresses its failure mechanism in carbonate-based electrolytes and further demonstrated its feasibility in lithium ion full cells for the first time. Our experiment provides the basis for the utilization of Cu2S in industrial-scale applications for large-scale electrical energy storage.

Octahedral spinel electrocatalysts for alkaline fuel cells.

Designing high-performance nonprecious electrocatalysts to replace Pt for the oxygen reduction reaction (ORR) has been a key challenge for advancing fuel cell technologies. Here, we report a systematic study of 15 different AB2O4/C spinel nanoparticles with well-controlled octahedral morphology. The 3 most active ORR electrocatalysts were MnCo2O4/C, CoMn2O4/C, and CoFe2O4/C. CoMn2O4/C exhibited a half-wave potential of 0.89 V in 1 M KOH, equal to the benchmark activity of Pt/C, which was ascribed to charge transfer between Co and Mn, as evidenced by X-ray absorption spectroscopy. Scanning transmission electron microscopy (STEM) provided atomic-scale, spatially resolved images, and high-energy-resolution electron-loss near-edge structure (ELNES) enabled fingerprinting the local chemical environment around the active sites. The most active MnCo2O4/C was shown to have a unique Co-Mn core-shell structure. ELNES spectra indicate that the Co in the core is predominantly Co2.7+ while in the shell, it is mainly Co2+ Broader Mn ELNES spectra indicate less-ordered nearest oxygen neighbors. Co in the shell occupies mainly tetrahedral sites, which are likely candidates as the active sites for the ORR. Such microscopic-level investigation probes the heterogeneous electronic structure at the single-nanoparticle level, and may provide a more rational basis for the design of electrocatalysts for alkaline fuel cells.