Insights into the in vitro digestibility and rheology properties of myofibrillar protein with different incorporation types of curdlan.

This study investigated the effects of two forms of curdlan, namely curdlan thermoreversibility (CT) and curdlan powder (CP), on in vitro digestion and viscoelastic properties of myofibrillar protein (MP). As the level of curdlan (0.1-0.5%) increased, pepsin digestibility and pancreatin digestibility significantly decreased, active sulfhydryl group also decreased, while surface hydrophobicity and total sulfhydryl groups increased. Meanwhile, curdlan enhanced the secondary and tertiary structures of MP. As the pepsin digest, α-helix gradually transformed into random coil. Furthermore, the viscosity, storage modulus (G") and loss modulus (G') increased with the CT or CP addition. After in vitro digestion, the viscoelasticity significantly decreased with a dose-response. Molecular dynamics simulations showed hydrogen bond formation (2.86 on average) between MP and curdlan contributing to reduced radius of gyration and solvent accessible surface area. Overall, this study highlighted curdlan as a promising ingredient to modulate structural properties and digestibility of MP, especially in pre-hydrated (CT) groups.

Microelectrode Arrays for Detection of Neural Activity in Depressed Rats: Enhanced Theta Activity in the Basolateral Amygdala.

Depression is a common and severely debilitating neuropsychiatric disorder. Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression. The basolateral amygdala (BLA) is crucial in the cognitive and physiological processing and control of emotion. However, due to the lack of detection tools, the neural activity of the BLA during depression is not well understood. In this study, a microelectrode array (MEA) based on the shape and anatomical location of the BLA in the brain was designed and manufactured. Rats were injected with lipopolysaccharide (LPS) for 7 consecutive days to induce depressive behavior. We used the MEA to detect neural activity in the BLA before modeling, during modeling, and after LPS administration on 7 consecutive days. The results showed that after LPS treatment, the spike firing of neurons in the BLA region of rats gradually became more intense, and the local field potential power also increased progressively. Further analysis revealed that after LPS administration, the spike firing of BLA neurons was predominantly in the theta rhythm, with obvious periodic firing characteristics appearing after the 7 d of LPS administration, and the relative power of the local field potential in the theta band also significantly increased. In summary, our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats, providing valuable guidance for research into the neural mechanisms of depression.

Tentacle Microelectrode Arrays Uncover Soft Boundary Neurons in Hippocampal CA1.

Hippocampal CA1 neurons show intense firing at specific spatial locations, modulated by isolated landmarks. However, the impact of real-world scene transitions on neuronal activity remains unclear. Moreover, long-term neural recording during movement challenges device stability. Conventional rigid-based electrodes cause inflammatory responses, restricting recording durations. Inspired by the jellyfish tentacles, the multi-conductive layer ultra-flexible microelectrode arrays (MEAs) are developed. The tentacle MEAs ensure stable recordings during movement, thereby enabling the discovery of soft boundary neurons. The soft boundary neurons demonstrate high-frequency firing that aligns with the boundaries of scene transitions. Furthermore, the localization ability of soft boundary neurons improves with more scene transition boundaries, and their activity decreases when these boundaries are removed. The innovation of ultra-flexible, high-biocompatible tentacle MEAs improves the understanding of neural encoding in spatial cognition. They offer the potential for long-term in vivo recording of neural information, facilitating breakthroughs in the understanding and application of brain spatial navigation mehanisms.

Systematic Transcriptome Profiling of hPSC-derived Osteoblasts Unveils CORIN's Mastery in Governing Osteogenesis Through CEBPD Modulation.

The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect hPSC-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide ChIP enrichment and mechanistic studies show that p38 MAPK-mediated CEBPD upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in MSCs exerts a negative regulatory effect on osteogenesis through a similar mechanism. ChIP-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.

A Review of Conductive Hydrogel-Based Wearable Temperature Sensors.

Conductive hydrogel has garnered significant attention as an emergent candidate for diverse wearable sensors, owing to its remarkable and tailorable properties such as flexibility, biocompatibility, and strong electrical conductivity. These attributes make it highly suitable for various wearable sensor applications (e.g., biophysical, bioelectrical, and biochemical sensors) that can monitor human health conditions and provide timely interventions. Among these applications, conductive hydrogel-based wearable temperature sensors are especially important for healthcare and disease surveillance. This review aims to provide a comprehensive overview of conductive hydrogel-based wearable temperature sensors. First, this work summarizes different types of conductive fillers-based hydrogel, highlighting their recent developments and advantages as wearable temperature sensors. Next, this work discusses the sensing characteristics of conductive hydrogel-based wearable temperature sensors, focusing on sensitivity, dynamic stability, stretchability, and signal output. Then, state-of-the-art applications are introduced, ranging from body temperature detection and wound temperature detection to disease monitoring. Finally, this work identifies the remaining challenges and prospects facing this field. By addressing these challenges with potential solutions, this review hopes to shed some light on future research and innovations in this promising field.

Ba2Ga2F6(IO3)(PO4): the first fluoride-containing iodate-phosphate with a 1D [Ga2F6(IO3)(PO4)]4- helix chain.

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

Pembrolizumab in an HIV-infected patient with glioblastoma.

Persons living with human immunodeficiency virus (PLWH) carry increased risk for developing malignancies, including glioblastoma. Despite extensive investigations, both human immunodeficiency virus (HIV) and glioblastoma are incurable. Treatment for a patient with combined glioblastoma and HIV remains an unexplored need. Preliminary evidence suggests that immunotherapy may be effective for the simultaneous treatment of both HIV and cancer by reversing HIV latency and T cell exhaustion. We present a case of glioblastoma in a PLWH who was treated with pembrolizumab. Treatment was well tolerated and safe with a mixed response. Our patient did not develop any opportunistic infections, immune-related adverse events, or worsening of his immunodeficiency. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

Persons living with human immunodeficiency virus (PLWH) are at increased risk for cancers, including glioblastoma. Despite extensive research, both human immunodeficiency virus (HIV) and glioblastoma are incurable. The optimal treatment for concurrent HIV and glioblastoma is unknown. Early evidence suggests that immunotherapy can deplete residual HIV and restore immune function. We present a case of glioblastoma in a PLWH treated with immunotherapy. Treatment was well tolerated and safe. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus.

The globus pallidus internus (GPi) was considered a common target for stimulation in Parkinson's disease (PD). Located deep in the brain and of small size, pinpointing it during surgery is challenging. Multi-channel microelectrode arrays (MEAs) can provide micrometer-level precision functional localization, which can maximize the surgical outcome. In this paper, a 64-channel MEA modified by platinum nanoparticles with a detection site impedance of 61.1 kΩ was designed and prepared, and multiple channels could be synchronized to cover the target brain region and its neighboring regions so that the GPi could be identified quickly and accurately. The results of the implant trajectory indicate that, compared to the control side, there is a reduction in local field potential (LFP) power in multiple subregions of the upper central thalamus on the PD-induced side, while the remaining brain regions exhibit an increasing trend. When the MEA tip was positioned at 8,700 µm deep in the brain, the various characterizations of the spike signals, combined with the electrophysiological characteristics of the ß-segmental oscillations in PD, enabled MEAs to localize the GPi at the single-cell level. More precise localization could be achieved by utilizing the distinct characteristics of the internal capsule (ic), the thalamic reticular nucleus (Rt), and the peduncular part of the lateral hypothalamus (PLH) brain regions, as well as the relative positions of these brain structures. The MEAs designed in this study provide a new detection method and tool for functional localization of PD targets and PD pathogenesis at the cellular level.

Cu-optimized long-range interaction between Co nanoparticles and Co single atoms: Improved Fenton-like reaction activity.

The interplay between multi-atom assembly configurations and single atoms (SAs) has been gaining attention in research. However, the effect of long-term range interactions between SAs and multi-atom assemblies on the orbital filling characteristics has yet to be investigated. In this context, we introduced copper (Cu) doping to strengthen the interaction between cobalt (Co) nanoparticles (NPs) and Co SAs by promoting the spontaneous formation of Co-Cu alloy NPs that tends toward aggregation owing to its negative cohesive energy (-0.06454), instead of forming Cu SAs. The incorporation of Cu within the Co-Cu alloy NPs, compared to the pure Co NPs, significantly expedites the kinetics of peroxymonosulfate (PMS) oxidation processes on Co SAs. Unlike Co NPs, Co-Cu NPs facilitate electron rearrangement in the d orbitals (especially dz2 and dxz) near the Fermi level in Co SAs, thereby optimizing the dz2-O (PMS) and dxz-O (SO5-) orbital interaction. Eventually, the Co-Cu alloy NPs embedded in nitrogen-doped carbon (CC@CNC) catalysts rapidly eliminated 80.67% of 20 mg/L carbamazepine (CBZ) within 5 min. This performance significantly surpasses that of catalysts consisting solely of Co NPs in a similar matrix (C@CNC), which achieved a 58.99% reduction in 5 min. The quasi in situ characterization suggested that PMS acts as an electron donor and will transfer electrons to Co SAs, generating 1O2 for contaminant abatement. This study offers valuable insights into the mechanisms by which composite active sites formed through multi-atom assembly interact at the atomic orbital level to achieve high-efficiency PMS-based advanced oxidation processes at the atomic orbital level.

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions.

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

The pivotal role of phosphorus level gradient in regulating nitrogen cycle in wetland ecosystems.

Phosphorus (P) is one of key drivers in Earth's nitrogen (N) cycle, however, the global overview of the P-regulated microbial community structure and gene abundance carrying wetland N process remains to be investigated. The key environmental factors that influenced wetland N cycle were initially screened, verifying the central role P. More complex and stable community interaction can be established in rich (20 mg/kg < P ≤ 100 mg/kg) and surplus P groups (P > 100 mg/kg) compared to that in deficient P group (P ≤ 20 mg/kg), with enhanced participation of betaproteobacteria and actinobacteria (i.e., changed hub microorganisms). Accordingly, P-mediated variations in gene expression patterns can be expected. On the one hand, the gene responses to carbon (C), N, and P factors presented nearly synchronous variation, highlighting the potential C-N-P coupling cycle in wetland ecosystem. On the other hand, the gene sensitivity towards environmental factors was changed at different P levels. Overall, the P level gradient can influence N cycle in direct (i.e., influences on gene abundances) and indirect (i.e., influences on gene response to environmental factors) manners. These findings provide important insights for controlling the N cycle in wetland ecosystems, particularly in cases where P levels are limiting factors.

Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy.

The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

Copolyester toughened poly(lactic acid) biodegradable material prepared by in situ formation of polyethylene glycol and citric acid.

Polylactic acid (PLA) is a high-modulus, high-strength bio-based thermoplastic polyester with good biodegradability, which is currently a promising environmentally friendly material. However, its inherent brittleness has hindered its widespread use. In this study, we reported a simple and non-toxic strategy for toughening PLA, using biodegradable materials such as polyethylene glycol (PEG) and citric acid (CA) as precursors. Through reactive melt blending with PLA, PEG and CA form PEGCA copolyesters in situ during blending. At the same time, CA can react with PLA and PEG, forming a copolyester structure at the interface of the two phases, improving the interfacial compatibility between PEG and PEGCA with PLA. Fourier transform infrared spectroscopy confirms this. Experimental results show that when the content of PEG/CA reaches 15% (PLA/PEG/CA-15%) in the blends, the impact strength of the blend was 4.47 kJ m-2, and the maximum elongation at break was as high as 360.1%, which were about 2 and 44 times higher than those of pure PLA, respectively. Moreover, the tensile strength was still maintained at the level of 70%. This work can expand the application of PLA in food packaging and medical supplies.

Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations.

The striatum plays a crucial role in studying epilepsy, as it is involved in seizure generation and modulation of brain activity. To explore the complex interplay between the striatum and epilepsy, we engineered advanced microelectrode arrays (MEAs) specifically designed for precise monitoring of striatal electrophysiological activities in rats. These observations were made during and following seizure induction, particularly three and 7 days post-initial modeling. The modification of graphene oxide (GO)/poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)/platinu-m nanoparticles (PtNPs) demonstrated a marked reduction in impedance (10.5 ± 1.1 kΩ), and maintained exceptional stability, with impedance levels remaining consistently low (23 kΩ) even 14 days post-implantation. As seizure intensity escalated, we observed a corresponding increase in neuronal firing rates and local field potential power, with a notable shift towards higher frequency peaks and augmented inter-channel correlation. Significantly, during the grand mal seizures, theta and alpha bands became the dominant frequencies in the local field potential. Compared to the normal group, the spike firing rates on day 3 and 7 post-modeling were significantly higher, accompanied by a decreased firing interval. Power in both delta and theta bands exhibited an increasing trend, correlating with the duration of epilepsy. These findings offer valuable insights into the dynamic processes of striatal neural activity during the initial and latent phases of temporal lobe epilepsy and contribute to our understanding of the neural mechanisms underpinning epilepsy.

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.

Key Role of Vegetation Cover in Alleviating Microplastic-Enhanced Carbon Emissions.

Microplastics (MPs) are considered to influence fundamental biogeochemical processes, but the effects of plant residue-MP interactions on soil carbon turnover in urban greenspaces are virtually unknown. Here, an 84-day incubation experiment was constructed using four types of single-vegetation-covered soils (6 years), showing that polystyrene MP (PSMP) pollution caused an unexpectedly large increase in soil CO2 emissions. The additional CO2 originating from highly bioavailable active dissolved organic matter molecules (<380 °C, predominantly polysaccharides) was converted from persistent carbon (380-650 °C, predominantly aromatic compounds) rather than PSMP derivatives. However, the priming effect of PSMP derivatives was weakened in plant-driven soils (resistivity: shrub > tree > grass). This can be explained from two perspectives: (1) Plant residue-driven humification processes reduced the percentage of bioavailable active dissolved organic matter derived from the priming effects of PSMPs. (2) Plant residues accelerated bacterial community succession (dominated by plant residue types) but slowed fungal community demise (retained carbon turnover-related functional taxa), enabling specific enrichment of glycolysis, the citric acid cycle and the pentose phosphate pathway. These results provide a necessary theoretical basis to understand the role of plant residues in reducing PSMP harm at the ecological level and refresh knowledge about the importance of biodiversity for ecosystem stability.

Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Neuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks. STUDY DESIGN: We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks. STUDY RESULTS: The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance. CONCLUSIONS: Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.

N, S, and Cl tri-doped carbon boost the switching of radical to non-radical pathway in Fenton-like reactions: Synergism of N species and defects.

Heteroatom doping represents a promising strategy for enhancing the generation of singlet oxygen (1O2) during the activation of peroxymonosulfate (PMS) using carbon-based catalysts; however, it remains a formidable challenge. In this study, we systematically controlled the structure of metal-free carbon-based materials by introducing different heteroatoms to investigate their efficacy in degrading organic pollutants in water via PMS activation. The results of reactive oxygen species detection showed that the dominant free radical in the four samples was different: CN (•SO4- and •OH), CNS (•O2-), CNCl (1O2), and CNClS (1O2). This led to the transformation of active species from free radicals to non-free radicals. The tri-doped carbons with nitrogen, sulfur, and chlorine (CNClS) exhibited exceptional performance in PMS activation and achieved a remarkable degradation efficiency of 95% within just 6 min for tetracycline. Moreover, a strong linear correlation was observed between the ratio of pyridine-N/graphite-N and ID/IG with the yield of 1O2, indicating that N species and defects play a crucial role in CNClS as they facilitate the transition from radical to non-radical pathways during PMS activation. These findings highlight the possibility that adjustable tri-heteroatom doping will expand the Fenton-like reaction for the treatment of actual wastewater.

Supramolecular assembly-induced electrochemiluminescence enhancement of gold nanoclusters for hemoglobin detection.

Gold nanoclusters (Au NCs) with excellent optical properties and biocompatibility have become one of the most promising electrochemiluminescence (ECL) emitters. However, the low efficiency and poor stability of Au NCs restrict their applications in ECL. Herein, by supramolecular assembly of L-arginine (Arg) and 4-hydroxy-2-mercapto-6-methylpyrimidine (MTU) on the surface of Au NCs, Arg/MTU-Au NCs with enhanced ECL efficiency and stability were prepared. Compared with the MTU-stabilized Au NCs (MTU-Au NCs), the ECL efficiency of Arg/MTU-Au NCs increased by 24.8 times. As a proof-of-concept, a sensitive biosensing platform was constructed for sensitive detection of hemoglobin (Hb) in urine using Arg/MTU-Au NCs as ECL emitters. The proposed ECL detection platform provides a feasible strategy for the detection of biomarkers in urine and has broad application prospects in disease screening and clinical marker detection.