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The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.
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Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.
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Planar Josephson junctions are predicted to host Majorana zero modes. The material platforms in previous studies are two-dimensional electron gases (InAs, InSb, InAsSb, and HgTe) coupled to a superconductor such as Al or Nb. Here, we introduce a new material platform for planar JJs, the PbTe-Pb hybrid. The semiconductor, PbTe, was grown as a thin film via selective area epitaxy. The Josephson junction was defined by a shadow wall during the deposition of superconductor Pb. Scanning transmission electron microscopy reveals a sharp semiconductor-superconductor interface. Gate-tunable supercurrents and multiple Andreev reflections are observed. A perpendicular magnetic field causes interference patterns of the switching current, exhibiting Fraunhofer-like and SQUID-like behaviors. We further demonstrate a prototype device for Majorana detection wherein phase bias and tunneling spectroscopy are applicable.
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This study investigated differences in adult-child language interactions when parents and their three-to-four-year old children engage in wordless book reading, text-and-picture book reading and a small-world toy play activity. Twenty-two parents recorded themselves completing each activity at home with their child. Parent input was compared across contexts, focusing on interactive and conceptual domains: use of open prompts, expansions or extensions of children's utterances, and use of decontextualised (abstract) language. Use of linguistic expansions was greater during book reading than toy play. Parents used open questions and added contingent conceptual information more often when reading wordless books than in both other conditions. Findings suggest that wordless books may combine the benefits of open-endedness and linguistic content based around a narrative. Parents' use of abstract language also varied by condition. This study extends understanding of the role of activity context in shaping children's language learning environments.
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Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.
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Engineered muscle fibers are attracting interest in bio-actuator research as they can contribute to the fabrication of actuators with a high power/size ratio for micro-robots. These fibers require to be stretched during culture for functional regulation as actuators and require a fixation on a rigid substrate for stretching in culture and evaluation of mechanical properties, such as Young's modulus and contraction force. However, the conventional fixation methods for muscle fibers have many restrictions as they are not repeatable and the connection between fixation part and the muscle fibers detaches during culture; therefore, the fixation becomes weak during culture, and direct measurement of the muscle fibers' mechanical properties by a force sensor is difficult. Therefore, we propose a facile and repeatable fixation method for muscle fibers by mixing magnetite nanoparticles at both ends of the muscle fibers to fabricate magnetic ends. The fiber can be easily attached and detached repeatedly by manipulating a magnet that applies a magnetic force larger than 3 mN to the magnetic ends. Thus, the muscle fiber can be stretched fiber during culture for functional regulation, transported between the culture dish and measurement system, and directly connected to the force sensor for measurement with magnetic ends. The muscle fiber connected with magnetic ends have a long lifetime (â¼4 weeks) and the cells inside had the morphology of a skeletal muscle. Moreover, the muscle fiber showed a contraction (specific force of 1.02 mN mm-2) synchronized with electrical stimulation, confirming the muscle fiber fabricated and cultured using our method had similar morphology and function as bio-actuators in previous research. This research demonstrates the advantages of the fixation method using muscle fibers with magnetic ends; the fibers are stretched during culture, and the transportation and force measurement of weak and tiny muscle fibers could be finished in 1 min.
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Contração Muscular , Fibras Musculares Esqueléticas , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Fenômenos Mecânicos , Fenômenos MagnéticosRESUMO
The numerous beneficial probiotic properties of Lactobacillus reuteri (L. reuteri) include decreasing metabolic syndrome, preventing disorders linked to oxidative stress, improving gut flora imbalances, controlling immunological function, and extending life span. Exposure to ionizing radiation is closely associated with several disorders. We examined the protective and salvaging effects of L. reuteri on ionizing radiation-induced injury to the intestinal tract, reproductive system, and nervous system of Drosophila melanogaster. We also examined its effects on lifespan, antioxidant capacity, progeny development, and behavioral aspects to assess the interaction between L. reuteri and ionizing radiation-induced injury. The findings demonstrated that L. reuteri improved the median survival time following irradiation and greatly extended its lifespan. In addition, it raised SOD activity, reduced ROS levels in intestinal epithelial cells, and increased the quantity of intestinal stem cells. Furthermore, L. reuteri enhanced the adult male flies' capacity to move. It also successfully safeguarded the generations' growth and development. L. reuteri dramatically enhanced expression of the AMPKα gene and regulated expression of its pathway-related gene, mTOR, as well as the autophagy-related genes Atg1 and Atg5 in female Drosophila exposed to irradiation. Notably, no prior reports have been made on the possible effects of L. reuteri on injuries caused by irradiation. As a result, our research offers important new information regarding L. reuteri's possible role as a shield against ionizing radiation-induced injury.
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Limosilactobacillus reuteri , Probióticos , Animais , Masculino , Feminino , Lactobacillus , Drosophila melanogaster , Intestinos , Radiação Ionizante , Probióticos/farmacologiaRESUMO
Electrochemical CO2 transformation to fuels and chemicals is an effective strategy for conversion of renewable electric energy into storable chemical energy in combination with reducing green-house gas emission. Metal-nitrogen-carbon (M-N-C) single atom catalysts (SAC) have shown great potential in the electrochemical CO2 reduction reaction (CO2RR). However, exploring advanced SACs with simultaneously high catalytic activity and high product selectivity remains a great challenge. In this study, density functional theory (DFT) calculations are combined with machine learning (ML) for rapid and high-throughput screening of high performance CO reduction catalysts. Firstly, the electrochemical properties of 99 M-N-C SACs were calculated by DFT and used as a database. By using different machine learning models with simple features, the investigated SACs were expanded from 99 to 297. Through several effective indicators of catalyst stability, inhibition of the hydrogen evolution reaction, and CO adsorption strength, 33 SACs were finally selected. The catalytic activity and selectivity of the remaining 33 SACs were explored by micro-kinetic simulation based on Marcus theory. Among all the studied SACs, Mn-NC2, Pt-NC2, and Au-NC2 deliver the best catalytic performance and can be used as potential catalysts for CO2/CO conversion to hydrocarbons with high energy density. This effective screening method using a machine learning algorithm can promote the exploration of CO2RR catalysts and significantly reduce the simulation cost.
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Injuries and subclinical effects from exposure to blasts are of significant concern in military operational settings, including tactical training, and are associated with self-reported concussion-like symptomology and physiological changes such as increased intestinal permeability (IP), which was investigated in this study. Time-series gene expression and IP biomarker data were generated from "breachers" exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre-, post-, and follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and taking longer to think, dissipating ~16 h following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p = 0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n = 23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mild traumatic brain injury and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive functioning. These preliminary findings show for the first time within real-world military operational settings that exposures to blast can contribute to IP.
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Traumatismos por Explosões , Concussão Encefálica , Militares , Humanos , Masculino , Militares/psicologia , Função da Barreira Intestinal , Traumatismos por Explosões/complicações , Concussão Encefálica/complicações , BiomarcadoresRESUMO
Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.
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Traumatismos por Explosões , Concussão Encefálica , Lesões Encefálicas , Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Estados Unidos/epidemiologia , Veteranos/psicologia , Lesões Encefálicas/psicologia , Militares/psicologia , Concussão Encefálica/complicações , Traumatismos por Explosões/complicações , Sono , Transtornos de Estresse Pós-Traumáticos/psicologia , Guerra do Iraque 2003-2011 , Campanha Afegã de 2001- , Estudos Observacionais como AssuntoRESUMO
OBJECTIVES: To investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6 A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. MATERIALS AND METHODS: The efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would-healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT-PCR, MeRIP-qPCR, immunofluorescence, and immunohistochemistry. RESULTS: STM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial-mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells. CONCLUSIONS: The combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti-tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC.
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It is believed that polysaccharides will become a focal point for future production of food, pharmaceuticals, and materials due to their ubiquitous and renewable nature, as well as their exceptional properties that have been extensively validated in the fields of nutrition, healthcare, and materials. Sulfated polysaccharides derived from seaweed sources have attracted considerable attention owing to their distinctive structures and properties. The genus Codium, represented by the species C. fragile, holds significance as a vital economic green seaweed and serves as a traditional Chinese medicinal herb. To date, the cell walls of the genus Codium have been found to contain at least four types of sulfated polysaccharides, specifically pyruvylated ß-d-galactan sulfates, sulfated arabinogalactans, sulfated ß-l-arabinans, and sulfated ß-d-mannans. These sulfated polysaccharides exhibit diverse biofunctions, including anticoagulant, immune-enhancing, anticancer, antioxidant activities, and drug-carrying capacity. This review explores the structural and biofunctional diversity of sulfated polysaccharides derived from the genus Codium. Additionally, in addressing the impending challenges within the industrialization of these polysaccharides, encompassing concerns regarding scale-up production and quality control, we outline potential strategies to address these challenges from the perspectives of raw materials, extraction processes, purification technologies, and methods for quality control.
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Clorófitas , Alga Marinha , Sulfatos/química , Clorófitas/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Alga Marinha/química , Mananas , Anticoagulantes/químicaRESUMO
Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules (p < 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p < 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability.
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Encéfalo , Ideação Suicida , Suicídio , Transcriptoma , Humanos , Feminino , Masculino , Transcriptoma/genética , Suicídio/psicologia , Adulto , Encéfalo/metabolismo , Pessoa de Meia-Idade , Redes Reguladoras de Genes/genética , Depressão/genética , Depressão/sangue , Inflamação/genética , Inflamação/sangueRESUMO
Inherent "soft" ionic lattice nature of halide perovskite quantum dots (QDs), triggered by the weak Pb-X (X=Cl, Br, I) bond, is recognized as the primary culprit for their serious instability. A promising way is to construct exceedingly strong ionic interaction inside the QDs and increase their crystal cohesive energy by substituting the interior X- with highly electronegative F- , however, which is challenging and hitherto remains unreported. Here, a "whole-body" fluorination strategy is proposed for strengthening the interior bonding architecture of QDs, wherein the F- are uniformly distributed throughout the whole nanocrystal encompassing both the interior lattice and surface, successfully stabilizing their "soft" crystal lattice and passivating surface defects. This approach effectively mitigates their intrinsic instability issues including light-induced phase segregation. As a result, light-emitting devices based on these QDs exhibit exceptional efficiency and remarkable stability.
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We introduced a label-free sensing system based on an array of microring resonators (MRRs) which was successfully employed for human serum albumin (HSA) detection. The sensing-ring surface was functionalized to immobilize anti-HSA, facilitating HSA binding. Our refractive index sensing system demonstrates high sensitivity at 168 nm/RIU and a low limit of detection (LOD) of 63.54 ng/mL, closely comparable to current HSA detection methods. These findings confirm the potential of MRRs as biocompatible sensors for HSA detection. This system holds great promise as an innovative platform for the detection of HSA, carrying significant importance in medical diagnostics.
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Técnicas Biossensoriais , Refratometria , Humanos , Limite de DetecçãoRESUMO
Trivalent Au ions are easily reduced to be zerovalent atoms by coexisting reductant reagents, resulting in the subsequent accumulation of Au atoms and formation of plasmonic nanostructures. In the absence of stabilizers or presence of weak stabilizers, aggregative growth of Au nanoparticles (NPs) always occurs, and unregular multidimensional Au materials are consequently constructed. Herein, the addition of nanomole-level mercury ions can efficiently prevent the epitaxial accumulation of Au atoms, and separated Au NPs with mediated morphologies and superior plasmonic characteristics are obtained. Experimental results and theoretical simulation demonstrate the Hg-concentration-reliant formation of plasmonic nanostructures with their mediated sizes and shapes in the presence of weak reductants. Moreover, the sensitive plasmonic responses of reaction systems exhibit selectivity comparable to that of Hg species. As a concept of proof, polymeric carbon dots (CDs) were used as the initial reductant, and the reactions between trivalent Au and CDs were studies. Significantly, Hg atoms prevent the epitaxial accumulation of Au atoms, and plasmonic NPs with decreased sizes were in situ synthesized, corresponding to varied surface plasmonic resonance absorption performance of the CD-induced hybrids. Moreover, with the integration of sensing substrates of CD-doped hydrogels, superior response stabilities, analysis selectivity, and sensitivity of Hg2+ ions were achieved on the basis of the mercury-mediated in situ chemical reactions between trivalent Au ions and reductant CDs. Consequently, a high-performance sensing strategy with the use of Au NP-staining hydrogels (nanostaining hydrogels) was exhibited. In addition to Hg sensing, the nanostaining hydrogels facilitated by doping of emerging materials and advanced chem/biostrategies can be developed as high-performance on-site monitoring routes to various pollutant species.
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Disorder is the primary obstacle in the current Majorana nanowire experiments. Reducing disorder or achieving ballistic transport is thus of paramount importance. In clean and ballistic nanowire devices, quantized conductance is expected, with plateau quality serving as a benchmark for disorder assessment. Here, we introduce ballistic PbTe nanowire devices grown by using the selective-area-growth (SAG) technique. Quantized conductance plateaus in units of 2e2/h are observed at zero magnetic field. This observation represents an advancement in diminishing disorder within SAG nanowires as most of the previously studied SAG nanowires (InSb or InAs) have not exhibited zero-field ballistic transport. Notably, the plateau values indicate that the ubiquitous valley degeneracy in PbTe is lifted in nanowire devices. This degeneracy lifting addresses an additional concern in the pursuit of Majorana realization. Moreover, these ballistic PbTe nanowires may enable the search for clean signatures of the spin-orbit helical gap in future devices.
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Ultralong organic phosphorescence (UOP) materials have attracted considerable attention in recent years. Herein, a new type of flexible films is fabricated by doping amphipathic pyrene tetrasulfonic acid sodium salts into amorphous poly(vinyl alcohol) matrix, which enables the realization of color-tunable UOP spanning from orange-red to green after excitation light is switched off. Interestingly, precise control of the proportion of isolated-molecular and aggregated-state phosphorescence is demonstrated for colorful afterglow using photo-activation. An increase in the dynamic phosphorescence lifetime of isolated molecules is observed from 894.75 to 1735.71 ms following an 8 min irradiation under ambient conditions. The photo-activation, however, showed little influence on aggreated-state phosphorescence. This flexible and processable film exhibits versatile applications in multicolor afterglow displays, ultraviolet detection, multilevel information encryption, etc. This study not only provides a strategy for the rational regulation of UOP colors but also expands the application potential of color-tunable UOP materials.
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Chemical oxygen demand (COD) is an important indicator for monitoring the quality of seawater. The COD of seawater reflects the levels of organic pollutants in the water. Methods that are commonly used to measure the COD of seawater have high accuracy, good repeatability, and low costs. However, using them for the in situ real-time monitoring of the COD of seawater is unfavorable because they require complex procedures and a long measurement time and may cause pollution to the environment. This paper reports on an optical sensor that accurately determines the COD of seawater in situ. The COD determination is based on the absorption of ultraviolet and visible lights with different wavelengths by organic matter in the water. Single-point LEDs emitting lights with different wavelengths (254, 265, 280, and 546 nm) were used as sources of excitation lights, and photodiodes were used as receiving devices. The optical system, circuit system, and mechanical structure of the sensor were efficiently integrated. The inversion of the COD of seawater was obtained after turbidity correction using the multiple linear regression algorithm. The maximum measurement error, detection limit, and repeatability of the sensor were 5%, 0.05 mg/l, and 0.62%, respectively. Moreover, the R2 values for correlations between COD values and absorbance values measured at three wavelengths (254, 265, and 280 nm) were above 0.99. Overall, the sensor is suitable for the in situ real-time monitoring of the COD of seawater. It requires a short measurement time and generates no pollution.
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BACKGROUND: To develop an ultrasound scoring system for placenta accreta spectrum (PAS), evaluate its diagnostic value, and provide a practical approach to prenatal diagnosis of PAS. METHODS: A total of 532 pregnant women (n = 184 no PAS, n = 120 placenta accreta, n = 189 placenta increta, n = 39 placenta percreta) at high-risk for placenta accreta who delivered in the Third Affiliated Hospital of Zhengzhou University between January 2021 and December 2022 underwent prenatal ultrasound to evaluate placental invasion. An ultrasound scoring system that included placental and cervical morphology and history of cesarean section was created. Each feature was assigned a score of 0 ~ 2, according to severity. Thresholds for the total ultrasound score that discriminated between no PAS, placenta accreta, placenta increta, and placenta percreta were calculated. RESULTS: Univariate and multivariate regression analysis identified seven indicators of PAS that were included in the ultrasound scoring system, including placental location, placental thickness, presence/absence of the retroplacental space, thickness of the retroplacental myometrium, presence/absence of placental lacunae, retroplacental myometrial blood flow and history of cesarean section. Using the final ultrasound scoring system, no PAS is diagnosed at a total score < 5, placenta accreta or placenta increta is diagnosed at a total score 5-10, and placenta percreta is diagnosed at a total score ≥ 10. CONCLUSIONS: This study identified seven indicators of PAS and included them in an ultrasound scoring system that has good diagnostic efficacy and clinical utility. TRIAL REGISTRATION: ChiCTR2300069261 (retrospectively registered on 10/03/2023).