Surveying biomedical relation extraction: a critical examination of current datasets and the proposal of a new resource.

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases.

Impact of viral telomeric repeat sequences on herpesvirus vector vaccine integration and persistence.

Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected billions of chickens from a deadly MDV infection. It is also among the most common vaccine vectors providing protection against a plethora of pathogens. HVT establishes latency in T-cells, allowing the vaccine virus to persist in the host for life. Intriguingly, the HVT genome contains telomeric repeat arrays (TMRs) at both ends; however, their role in the HVT life cycle remains elusive. We have previously shown that similar TMRs in the MDV genome facilitate its integration into host telomeres, which ensures efficient maintenance of the virus genome during latency and tumorigenesis. In this study, we investigated the role of the TMRs in HVT genome integration, latency, and reactivation in vitro and in vivo. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (vΔTMR) that efficiently replicated in cell culture. We could demonstrate that wild type HVT integrates at the ends of chromosomes containing the telomeres in T-cells, while integration was severely impaired in the absence of the TMRs. To assess the role of TMRs in vivo, we infected one-day-old chickens with HVT or vΔTMR. vΔTMR loads were significantly reduced in the blood and hardly any virus was transported to the feather follicle epithelium where the virus is commonly shed. Strikingly, latency in the spleen and reactivation of the virus were severely impaired in the absence of the TMRs, indicating that the TMRs are crucial for the establishment of latency and reactivation of HVT. Our findings revealed that the TMRs facilitate integration of the HVT genome into host chromosomes, which ensures efficient persistence in the host, reactivation, and transport of the virus to the skin.

The past 10 years of molecular ferroelectrics: structures, design, and properties.

Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc., the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.

Neuronal small extracellular vesicles carrying miR-181c-5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C-δ/glutamate transporter-1 axis in astrocytes.

Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter-1 (GLT-1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR-181c-5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV-derived miR-181c-5p interacted with protein kinase C-delta (PKCδ), downregulated PKCδ and GLT-1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR-181c-5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy.

Rational Design of 2D Metal Halide Perovskites with Low Congruent Melting Temperature and Large Melt-Processable Window.

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

Unraveling the role of hepatitis B virus DNA integration in B-cell lymphomagenesis.

BACKGROUND: Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. METHODS: Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. RESULTS: A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. CONCLUSION: Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.

ALDOA coordinates PDE3A through the ß-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations.

Lung cancer has a high incidence rate and requires more effective treatment strategies and drug options for clinical patients. EGFR is a common genetic alteration event in lung cancer that affects patient survival and drug strategy. Our study discovered aberrant aldolase A (ALDOA) expression and dysfunction in lung cancer patients with EGFR mutations. In addition to investigating relevant metabolic processes like glucose uptake, lactate production, and ATPase activity, we examined multi-omics profiles (transcriptomics, proteomics, and pull-down assays). It was observed that phosphodiesterase 3A (PDE3A) enzyme and ALDOA exhibit correlation, and furthermore, they impact M2 macrophage polarization through ß-catenin and downstream ID3. In addition to demonstrating the aforementioned mechanism of action, our experiments discovered that the PDE3 inhibitor trequinsin has a substantial impact on lung cancer cell lines with EGFR mutants. The trequinsin medication was found to decrease the M2 macrophage polarization status and several cancer phenotypes, in addition to transduction. These findings have potential prognostic and therapeutic applications for clinical patients with EGFR mutation and lung cancer.

Sustained Release-Driven Interface Engineering Enables Fast Charging Lithium Metal Batteries.

LiNO3 has attracted intensive attention as a promising electrolyte additive to regulate Li deposition behavior as it can form favorable Li3N, LiNxOy species to improve the interfacial stability. However, the inferior solubility in carbonate-based electrolyte restricts its application in high-voltage Li metal batteries. Herein, an artificial composite layer (referred to as PML) composed of LiNO3 and PMMA is rationally designed on Li surface. The PML layer serves as a reservoir for LiNO3 release gradually to the electrolyte during cycling, guaranteeing the stability of SEI layer for uniform Li deposition. The PMMA matrix not only links the nitrogen-containing species for uniform ionic conductivity but also can be coordinated with Li for rapid Li ions migration, resulting in homogenous Li-ion flux and dendrite-free morphology. As a result, stable and dendrite-free plating/stripping behaviors of Li metal anodes are achieved even at an ultrahigh current density of 20 mA cm-2 (>570 h) and large areal capacity of 10 mAh cm-2 (>1200 h). Moreover, the Li||LiFePO4 full cell using PML-Li anode undergoes stable cycling for 2000 cycles with high-capacity retention of 94.8%. This facile strategy will widen the potential application of LiNO3 in carbonate-based electrolyte for practical LMBs.

Photon blockade with high photon occupation via cavity electromagnetically induced transparency.

Photon blockade (PB) is one of the effective methods to generate single-photon sources. In general, both the PB effect with the significant sub-Poissonian statistics and a large mean photon number are desired to guarantee the brightness and the purity of single-photon sources. Here, we propose to obtain the PB effect at the cavity dark-state polariton (DSP) using a cavity Λ-type electromagnetically induced transparency (EIT) system with and without the two-photon dissipation (TPD). In the Raman resonance case, the PB effect at the DSP could by realized by using the TPD process in the weak or intermediate coupling regime, which accompanies with near unity transmission, i.e., very high photon occupation. In the slightly detuned Raman resonance case, the excited state is induced into the components of the DSP, and the atomic dissipation path is added into the two-photon excitation paths. Thus, the PB effect at the DSP can be obtained due to the quantum destructive interference (QDI) in the strong coupling regime, which can be further enhanced using the TPD process. Due to the slight detuning, the PB effect still remains high photon occupation and has highly tunability. This work provides an alternative way to manipulate the photon statistics by the PB effect and has potential applications in generating single-photon sources with high brightness and purity.

Revealing the Polarizations of Molecular Ferroelectrics via SHG Polarimetry at the Nanoscale.

Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.