"Very" Very Late Stent Thrombosis: A Detailed Look at Two Cases.

Although percutaneous coronary intervention (PCI) has radically transformed the scope of treating coronary artery disease with stenting, stent thrombosis (STh) remains a feared complication. Very late STh, a rare complication after PCI, refers to STh occurring greater than one year after post-stent implantation. An even rarer phenomenon, "very" very late stent thrombosis (VVLST), is described in the literature as STh occurring more than five years post-stent implantation. To our knowledge, there are only 10 case reports and one case series describing VVLST. We discuss two additional complex clinical cases of VVLST presenting as ST-elevation myocardial infarction. We highlight epidemiology, pathophysiology, presentation, diagnostic methods, treatment approach, associated complications, and the need for more extensive future work to minimize the risk of VVLST.

Reversibly Reactive Affinity Selection-Mass Spectrometry Enables Identification of Covalent Peptide Binders.

Covalent peptide binders have found applications as activity-based probes and as irreversible therapeutic inhibitors. Currently, there is no rapid, label-free, and tunable affinity selection platform to enrich covalent reactive peptide binders from synthetic libraries. We address this challenge by developing a reversibly reactive affinity selection platform termed ReAct-ASMS enabled by tandem high-resolution mass spectrometry (MS/MS) to identify covalent peptide binders to native protein targets. It uses mixed disulfide-containing peptides to build reversible peptide-protein conjugates that can enrich for covalent variants, which can be sequenced by MS/MS after reduction. Using this platform, we identified covalent peptide binders against two oncoproteins, human papillomavirus 16 early protein 6 (HPV16 E6) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 protein (Pin1). The resulting peptide binders efficiently and selectively cross-link Cys58 of E6 at 37 °C and Cys113 of Pin1 at room temperature, respectively. ReAct-ASMS enables the identification of highly selective covalent peptide binders for diverse molecular targets, introducing an applicable platform to assist preclinical therapeutic development pipelines.

Ultrathin Boundary-Less SnO2 Films with Surface-Activated Two-Dimensional Nanograins Enable Fast and Sensitive Hydrogen Gas Sensing.

Fast and reliable semiconductor hydrogen sensors are crucially important for the large-scale utilization of hydrogen energy. One major challenge that hinders their practical application is the elevated temperature required, arising from undesirable surface passivation and grain-boundary-dominated electron transportation in the conventional nanocrystalline sensing layers. To address this long-standing issue, in the present work, we report a class of highly reactive and boundary-less ultrathin SnO2 films, which are fabricated by the topochemical transformation of 2D SnO transferred from liquid Sn-Bi droplets. The ultrathin SnO2 films are purposely made to consist of well-crystallized quasi-2D nanograins with in-plane grain sizes going beyond 30 nm, whereby the hydroxyl adsorption and grain boundary side-effects are effectively suppressed, giving rise to an activated (101)-dominating dangling-bond surface and a surface-controlled electrical transportation with an exceptional electron mobility of 209 cm2 V-1 s-1. Our work provides a new cost-effective strategy to disruptively improve the gas reception and transduction of SnO2. The proposed chemiresistive sensors exhibit fast, sensitive, and selective hydrogen sensing performance at a much-reduced working temperature of 60 °C. The remarkable sensing performance as well as the simple and scalable fabrication process of the ultrathin SnO2 films render the thus-developed sensors attractive for long awaited practical applications in hydrogen-related industries.

Environmental DNA-based biodiversity profiling along the Houdong River in north-eastern Taiwan.

Background: This paper describes two datasets: species occurrences, which were determined by environmental DNA (eDNA) metabarcoding and their associated DNA sequences, originating from a research project which was carried out along the Houdong River (), Jiaoxi Township, Yilan, Taiwan. The Houdong River begins at an elevation of 860 m and flows for approximately 9 km before it empties into the Pacific Ocean. Meandering through mountains, hills, plains and alluvial valleys, this short river system is representative of the fluvial systems in Taiwan. The primary objective of this study was to determine eukaryotic species occurrences in the riverine ecosystem through the use of the eDNA analysis. The second goal was, based on the current dataset, to establish a metabarcoding eDNA data template that will be useful and replicable for all users, particularly the Taiwan community. The species occurrence data are accessible at the Global Biodiversity Information Facility (GBIF) portal and its associated DNA sequences have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI, respectively. A total of 12 water samples from the study yielded an average of 1.5 million reads. The subsequent species identification from the collected samples resulted in the classification of 432 Operational Taxonomic Units (OTUs) out of a total of 2,734. Furthermore, a total of 1,356 occurrences with taxon matches in GBIF were documented (excluding 4,941 incertae sedis, accessed 05-12-2023). These data will be of substantial importance for future species and habitat monitoring within the short river, such as assessment of biodiversity patterns across different elevations, zonations and time periods and its correlation to water quality, land uses and anthropogenic activities. Further, these datasets will be of importance for regional ecological studies, in particular the freshwater ecosystem and its status in the current global change scenarios. New information: The datasets are the first species diversity description of the Houdong River system using either eDNA or traditional monitoring processes.

Bi-directional charge transfer channels in highly crystalline carbon nitride enabling superior photocatalytic hydrogen evolution.

Introducing a donor-acceptor (D-A) unit is an effective approach to facilitate charge transfer in polymeric carbon nitride (PCN) and enhance photocatalytic performance. However, the introduction of hetero-molecules can lead to a decrease in crystallinity, limiting interlayer charge transfer and inhibiting further improvement. In this study, we constructed a novel D-A type carbon nitride with significantly higher crystallinity and a bi-directional charge transfer channel, which was achieved through 2,5-thiophenedicarboxylic acid (2,5-TDCA)-assisted self-assembly followed by KCl-templated calcination. The thiophene and cyano groups introduced serve as the electron donor and acceptor, respectively, enhancing in-plane electron delocalization. Additionally, introduced potassium ions are intercalated among the adjacent layers of carbon nitride, creating an interlayer charge transfer channel. Moreover, the highly ordered structure and improved crystallinity further facilitate charge transfer. As a result, the as-prepared photocatalyst exhibits superior photocatalytic hydrogen evolution (PHE) activity of 7.449 mmol h-1 g-1, which is 6.03 times higher than that of pure carbon nitride. The strategy of developing crystalline D-A-structured carbon nitride with controlled in-plane and interlayer charge transfer opens new avenues for the design of carbon nitride with enhanced properties for PHE.

Development of an α-Klotho Recognizing High-Affinity Peptide Probe from In-Solution Enrichment.

The kidney, parathyroid gland, and choroid plexus express the aging-related transmembrane protein α-Klotho, a coreceptor of the fibroblast growth factor 23 (FGF23) receptor complex. Reduced α-Klotho levels are correlated with chronic kidney disease and other age-related diseases, wherein they are released from membranes into circulation. Klotho's potential physiological action as a hormone is of current scientific interest. Part of the challenges associated with advancing these studies, however, has been the long-standing difficulty in detecting soluble α-Klotho in biofluids. Here, we describe the discovery of peptides that recognize α-Klotho with high affinity and selectivity by applying in-solution size-exclusion-based affinity selection-mass spectrometry (AS-MS). After two rounds of AS-MS and subsequent N-terminal modifications, the peptides improved their binding affinity to α-Klotho by approximately 2300-fold compared to the reported starting peptide Pep-10, previously designed based on the C-terminal region of FGF23. The lead peptide binders were shown to enrich α-Klotho from cell lysates and to label α-Klotho in kidney cells. Our results further support the utility of in-solution, label-free AS-MS protocols to discover peptide-based binders to target proteins of interest with high affinity and selectivity, resulting in functional probes for biological studies.

Electrochemical Knocking-Down of Zn Metal Clusters into Single Atoms.

Single Atoms Catalysts (SACs) have emerged as a class of highly promising heterogeneous catalysts, where the traditional bottom-up synthesis approaches often encounter considerable challenges in relation to aggregation issues and poor stability. Consequently, achieving densely dispersed atomic species in a reliable and efficient manner remains a key focus in the field. Herein, we report a new facile electrochemical knock-down strategy for the formation of SACs, whereby the metal Zn clusters are transformed into single atoms. While a defect-rich substrate plays a pivotal role in capturing and stabilizing isolated Zn atoms, the feasibility of this novel strategy is demonstrated through a comprehensive investigation, combining experimental and theoretical studies. Furthermore, when studied in exploring for potential applications, the material prepared shows a remarkable improvement of 58.21% for the Li+ storage and delivers a capacity over 300 Wh kg-1 after 500 cycles upon the transformation of Zn clusters into single atoms.

AbDPP: Target-oriented antibody design with pretraining and prior biological structure knowledge.

Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target-oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning-based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP.

Challenges and Opportunities in Preserving Key Structural Features of 3D-Printed Metal/Covalent Organic Framework.

Metal-organic framework (MOF) and covalent organic framework (COF) are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features, such as large surface area, tunable pore size, and functional surfaces, which have significant values in various application areas. The emerging 3D printing technology further provides MOF and COFs (M/COFs) with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3D monoliths. However, the currently available 3D printing M/COFs strategy faces a major challenge of severe destruction of M/COFs' microstructural features, both during and after 3D printing. It is envisioned that preserving the microstructure of M/COFs in the 3D-printed monolith will bring a great improvement to the related applications. In this overview, the 3D-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered monoliths. Their differences in the properties, applications, and current research states are discussed. The up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3D printing are further discussed for the two types of 3D-printed M/COF. Throughout the analysis of the current states of 3D-printed M/COFs, the expected future research direction to achieve a highly preserved microstructure in the 3D monolith is proposed.

Structure of the p53 degradation complex from HPV16.

Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity is facilitated in part by the HPV early protein 6 (E6), which interacts with the E3-ligase E6AP, also known as UBE3A, to promote degradation of the tumor suppressor, p53. In this study, we present a single-particle cryoEM structure of the full-length E6AP protein in complex with HPV16 E6 (16E6) and p53, determined at a resolution of ~3.3 Å. Our structure reveals extensive protein-protein interactions between 16E6 and E6AP, explaining their picomolar binding affinity. These findings shed light on the molecular basis of the ternary complex, which has been pursued as a potential therapeutic target for HPV-driven cervical, anal, and oropharyngeal cancers over the last two decades. Understanding the structural and mechanistic underpinnings of this complex is crucial for developing effective therapies to combat HPV-induced cancers. Our findings may help to explain why previous attempts to disrupt this complex have failed to generate therapeutic modalities and suggest that current strategies should be reevaluated.

Diffuse Pneumonitis after Lutetium-177-PSMA-617 Treatment in a Patient with Metastatic Castration-Resistant Prostate Cancer.

We present the case of a patient with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) who received lutetium Lu-177 vipivotide tetraxetan (also known as 177Lu-PSMA-617) due to progressive disease despite chemotherapy, hormonal therapy and radiation, including palliative mediastinal and central nervous system radiation. He was subsequently hospitalised for worsening acute onset dyspnoea despite clinically responding to therapy. Interval imaging revealed progressive multifocal ground-glass opacities superimposed on a background of underlying peribronchovascular fibrosis. Further workup, including an extensive workup to identify a possible infectious aetiology, ruled out most aetiologies leaving radiation pneumonitis (RP), radiation recall pneumonitis (RRP) and drug-induced pneumonitis as possible diagnoses secondary to 177Lu -PSMA-617. The associated imaging findings of ground-glass opacities and consolidation can be like other aetiologies such as acute infection and subsequently may be treated incorrectly. In the use of theragnostics like 177Lu -PSMA-617, it is fundamental to apply the practices of radioprotection learnt from radiotherapy, as well as to consider prior radiotherapy treatments and their possible side effects when used in conjunction.

Nanofiltration Ceramic Membranes as a Feasible Two-Pronged Approach toward Desalination and Lithium Recovery.

Ceramic membranes are taking center stage for separation technologies in water treatment. Among them, ceramic nanofiltration membranes are at the forefront of membrane technologies. The desalination of seawater using ceramic nanofiltration membranes is a potential application toward increasing the global water supply and tackling water scarcity. However, while the high fabrication cost poses a challenge to their large-scale applications, high-value separation applications can help to offset the overall cost. In this regard, ceramic nanofiltration membranes can also be explored as a viable option for high-value lithium extraction from the waste seawater brine. In order to determine the potential of nanofiltration ceramic membranes for desalination and lithium recovery from seawater, the current efficiency of salt rejection across various operation parameters must be thoroughly evaluated. Specifically, the interactions between the Donnan exclusion, steric exclusion, zeta potential, and salt concentration play an important role in determining the salt rejection efficiency. Several strategies are then proposed to guide ceramic nanofiltration membranes toward potentially practical applications regarding desalination and lithium recovery.

Predictive Biomarkers of Immune Checkpoint Inhibitor-Based Mono- and Combination Therapies for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the most frequent and deadly human cancers worldwide. It has been shown that interaction between immune checkpoint receptors and ligands plays a crucial role in inhibition of T cell-mediated anti-tumor immune responses, thereby assisting tumor cells to evade the host immune surveillance. Therefore, several immune checkpoint inhibitors (ICIs) that selectively block immune checkpoint receptors or ligands have been developed as clinically effective and safe immunotherapeutic agents for treating HCC, including the inhibitors targeting cytotoxic T lymphocyte-associated antigen 4, programmed death 1, and programmed death ligand 1. In addition, various combinations of ICIs and other ICIs or tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors have also emerged as clinically beneficial treatments for HCC. However, the overall response rates of ICI mono-therapy and combination therapy in HCC patients remain unsatisfied, highlighting the urgent need for discovering valuable predictive biomarkers to achieve personalized therapy. This review comprehensively summarizes the literature-based evidence validating a variety of biomarkers with predictive significance for treatment responses and outcomes in HCC patients receiving various ICI-based mono- and combination therapies.

Switch Volmer-Heyrovsky to Volmer-Tafel Pathway for Efficient Acidic Electrocatalytic Hydrogen Evolution by Correlating Pt Single Atoms with Clusters.

As cost-effective catalysts, platinum (Pt) single-atom catalysts (SACs) have attracted substantial attention. However, most studies indicate that Pt SACs in acidic hydrogen evolution reaction (HER) follow the slow Volmer-Heyrovsky (VH) mechanism instead of the fast kinetic Volmer-Tafel (VT) pathway. Here, this work propose that the VH mechanism in Pt SACs can be switched to the faster VT pathway for efficient HER by correlating Pt single atoms (SAs) with Pt clusters (Cs). Our calculations reveal that the correlation between Pt SAs and Cs significantly impacts the electronic structure of exposed Pt atoms, lowering the adsorption barrier for atomic hydrogen and enabling a faster VT mechanism. To validate these findings, this work purposely synthesize three catalysts: l-Pt@MoS2, m-Pt@MoS2 and h-Pt@MoS2 with low, moderate, and high Pt-loading, having different distributions of Pt SAs and Cs. The m-Pt@MoS2 catalyst with properly correlating Pt SAs and Cs exhibits outstanding performance with an overpotential of 47 mV and Tafel slope of 32 mV dec-1. Further analysis of the Tafel values confirms that the m-Pt@MoS2 sample indeed follows the VT reaction mechanism, aligning with the theoretical findings. This study offers a deep understanding of the synergistic mechanism, paving a way for designing novel-advanced catalysts.

Potential PCR amplification bias in identifying complex ecological patterns: Higher species compositional homogeneity revealed in smaller-size coral reef zooplankton by metatranscriptomics.

PCR-based high-throughput sequencing has permitted comprehensive resolution analyses of zooplankton diversity dynamics. However, significant methodological issues still surround analyses of complex bulk community samples, not least as in prevailing PCR-based approaches. Marine drifting animals-zooplankton-play essential ecological roles in the pelagic ecosystem, transferring energy and elements to higher trophic levels, such as fishes, cetaceans and others. In the present study, we collected 48 size-fractionated zooplankton samples in the vicinity of a coral reef island with environmental gradients. To investigate the spatiotemporal dynamics of zooplankton diversity patterns and the effect of PCR amplification biases across these complex communities, we first took metatranscriptomics approach. Comprehensive computational analyses revealed a clear pattern of higher/lower homogeneity in smaller/larger zooplankton compositions across samples respectively. Our study thus suggests changes in the role of dispersal across the sizes. Next, we applied in silico PCR to the metatranscriptomics datasets, in order to estimate the extent of PCR amplification bias. Irrespective of stringency criteria, we observed clear separations of size fraction sample clusters in both metatranscriptomics and in silico datasets. In contrast, the pattern-smaller-fractioned communities had higher compositional homogeneity than larger ones-was observed in the metatranscriptomics data but not in the in silico datasets. To investigate this discrepancy further, we analysed the mismatches of widely used mitochondrial CO1 primers and identified priming site mismatches likely driving PCR-based biases. Our results suggest the use of metatranscriptomics or, although less ideal, redesigning the CO1 primers is necessary to circumvent these issues.

Electrophile Scanning Reveals Reactivity Hotspots for the Design of Covalent Peptide Binders.

Protein-protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides are well suited to target PPIs, which typically present with large surface areas lacking distinct features and deep binding pockets. To improve binding interactions with these topologies and advance the development of PPI-focused therapeutics, potential ligands can be equipped with electrophilic groups to enable binding through covalent mechanisms of action. We report a strategy termed electrophile scanning to identify reactivity hotspots in a known peptide ligand and demonstrate its application in a model PPI. Cysteine mutants of a known ligand are used to install protein-reactive modifiers via a palladium oxidative addition complex (Pd-OAC). Reactivity hotspots are revealed by cross-linking reactions with the target protein under physiological conditions. In a model PPI with the 9-mer peptide antigen VL9 and major histocompatibility complex (MHC) class I protein HLA-E, we identify two reactivity hotspots that afford up to 87% conversion to the protein-peptide conjugate within 4 h. The reactions are specific to the target protein in vitro and dependent on the peptide sequence. Moreover, the cross-linked peptide successfully inhibits molecular recognition of HLA-E by CD94-NKG2A possibly due to structural changes enacted at the PPI interface. The results illustrate the potential application of electrophile scanning as a tool for rapid discovery and development of covalent peptide binders.

Effects of propofol on presynaptic synapsin phosphorylation in the mouse brain in vivo.

The commonly used general anesthetic propofol can enhance the γ-aminobutyric acid-mediated inhibitory synaptic transmission and depress the glutamatergic excitatory synaptic transmission to achieve general anesthesia and other outcomes. In addition to the actions at postsynaptic sites, the modulation of presynaptic activity by propofol is thought to contribute to neurophysiological effects of the anesthetic, although potential targets of propofol within presynaptic nerve terminals are incompletely studied at present. In this study, we explored the possible linkage of propofol to synapsins, a family of neuron-specific phosphoproteins which are the most abundant proteins on presynaptic vesicles, in the adult mouse brain in vivo. We found that an intraperitoneal injection of propofol at a dose that caused loss of righting reflex increased basal levels of synapsin phosphorylation at the major representative phosphorylation sites (serine 9, serine 62/67, and serine 603) in the prefrontal cortex (PFC) of male and female mice. Propofol also elevated synapsin phosphorylation at these sites in the striatum and S9 and S62/67 phosphorylation in the hippocampus, while propofol had no effect on tyrosine hydroxylase phosphorylation in striatal nerve terminals. Total synapsin protein expression in the PFC, hippocampus, and striatum was not altered by propofol. These results reveal that synapsin could be a novel substrate of propofol in the presynaptic neurotransmitter release machinery. Propofol possesses the ability to upregulate synapsin phosphorylation in broad mouse brain regions.

Correlating Single-Atomic Ruthenium Interdistance with Long-Range Interaction Boosts Hydrogen Evolution Reaction Kinetics.

Correlated single-atom catalysts (c-SACs) with tailored intersite metal-metal interactions are superior to conventional catalysts with isolated metal sites. However, precise quantification of the single-atomic interdistance (SAD) in c-SACs is not yet achieved, which is essential for a crucial understanding and remarkable improvement of the correlated metal-site-governed catalytic reaction kinetics. Here, three Ru c-SACs are fabricated with precise SAD using a planar organometallic molecular design and π-π molecule-carbon nanotube confinement. This strategy results in graded SAD from 2.4 to 9.3 Å in the Ru c-SACs, wherein tailoring the Ru SAD into 7.0 Å generates an exceptionally high turnover frequency of 17.92 H2 s-1 and a remarkable mass activity of 100.4 A mg-1 under 50 and 100 mV overpotentials, respectively, which is superior to all the Ru-based catalysts reported previously. Furthermore, density functional theory calculations confirm that Ru SAD has a negative correlation with its d-band center owing to the long-range interactions induced by distinct local atomic geometries, resulting in an appropriate electrostatic potential and the highest catalytic activity on c-SACs with 7.0 Å Ru SAD. The present study promises an attractive methodology for experimentally quantifying the metal SAD to provide valuable insights into the catalytic mechanism of c-SACs.

Interfacial Synergy in Mo2C/MoC Heterostructure Promoting Sequential Polysulfide Conversion in High-Performance Lithium-Sulfur Battery.

A rational design of sulfur host is the key to conquering the"polysulfide shuttle effects" by accelerating the polysulfide conversion. Since the process involves solid-liquid-solid multistep phase transitions, purposely-engineered heterostructure catalysts with various active regions for catalyzing conversion steps correspondingly are beneficial to promote the overall conversion process. However, the functionalities of the materials surface and interface in heterostructure catalysts remain unclear. In this work, an Mo2C/MoC catalyst with abundant Mo2C surface-interface-MoC surface tri-active-region is developed by in situ converting the MoZn-metal organic framework. The experimental and simulation studies demonstrate the interface can catch long-chain polysulfides and promote their conversion. Instead, the Mo2C and MoC tend to accommodate the short-chain polysulfide and accelerate their conversion and the Li2S dissociation. Benefitting from the high catalytic ability, the Li-S battery assembled with the Mo2C/MoC-S cathode shows more discrete redox reactions and delivers a high initial capacity of 1603.6 mAh g-1 at 1 C charging-discharging rate, which is over twofolds of the one assembled using individual hosts, and 80.4% capacity can be maintained after 1000 cycles at 3 C rate. This work has demonstrated a novel synergy between the interface and material surface, which will help the future design of high-performance Li-S batteries.