The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins.

Vesicle trafficking is a fundamental process that allows for the sorting and transport of specific proteins (i.e., "cargoes") to different compartments of eukaryotic cells. Cargo recognition primarily occurs through coats and the associated proteins at the donor membrane. However, it remains unclear whether cargoes can also be selected at other stages of vesicle trafficking to further enhance the fidelity of the process. The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complex to facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EM structure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizes a subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complex assembly and its binding to SAC-containing proteins are indispensable for the trafficking of SAC-containing proteins and proper neuronal development in zebrafish. Our studies thus uncover that cargo proteins could be recognized in a sequence-specific manner downstream of a protein coat.

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.

Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.

Ubiquitous coexisting electron-mode couplings in high-temperature cuprate superconductors.

In conventional superconductors, electron-phonon coupling plays a dominant role in generating superconductivity. In high-temperature cuprate superconductors, the existence of electron coupling with phonons and other boson modes and its role in producing high-temperature superconductivity remain unclear. The evidence of electron-boson coupling mainly comes from angle-resolved photoemission (ARPES) observations of [Formula: see text]70-meV nodal dispersion kink and [Formula: see text]40-meV antinodal kink. However, the reported results are sporadic and the nature of the involved bosons is still under debate. Here we report findings of ubiquitous two coexisting electron-mode couplings in cuprate superconductors. By taking ultrahigh-resolution laser-based ARPES measurements, we found that the electrons are coupled simultaneously with two sharp modes at [Formula: see text]70meV and [Formula: see text]40meV in different superconductors with different dopings, over the entire momentum space and at different temperatures above and below the superconducting transition temperature. These observations favor phonons as the origin of the modes coupled with electrons and the observed electron-mode couplings are unusual because the associated energy scales do not exhibit an obvious energy shift across the superconducting transition. We further find that the well-known "peak-dip-hump" structure, which has long been considered a hallmark of superconductivity, is also omnipresent and consists of "peak-double dip-double hump" finer structures that originate from electron coupling with two sharp modes. These results provide a unified picture for the [Formula: see text]70-meV and [Formula: see text]40-meV energy scales and their evolutions with momentum, doping and temperature. They provide key information to understand the origin of these energy scales and their role in generating anomalous normal state and high-temperature superconductivity.

An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii.

Exocytosis is a key active process in cells by which proteins are released in bulk via the fusion of exocytic vesicles with the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein-mediated vesicle fusion with the plasma membrane is essential in most exocytotic pathways. In mammalian cells, the vesicular fusion step of exocytosis is normally mediated by Syntaxin-1 (Stx1) and SNAP25 family proteins (SNAP25 and SNAP23). However, in Toxoplasma gondii, a model organism of Apicomplexa, the only SNAP25 family protein, with a SNAP29-like molecular structure, is involved in vesicular fusion at the apicoplast. Here, we reveal that an unconventional SNARE complex comprising TgStx1, TgStx20, and TgStx21 mediates vesicular fusion at the plasma membrane. This complex is essential for the exocytosis of surface proteins and vesicular fusion at the apical annuli in T. gondii.

PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin α5.

PRELP is thought to be an inhibitor of the development and progression of a variety of malignancies. Metastasis is a major cause of death in patients with colorectal cancer, but the mechanism underlying the role of PRELP in colorectal cancer metastasis remains poorly understood. In this study, we found that PRELP was significantly higher in metastatic tissues than in non-metastatic tissues of colorectal cancer and was closely associated with poor prognosis of colorectal cancer patients. PRELP promotes growth and metastasis of colorectal cancer cells. PRELP reduces cell stiffness and adhesion. PRELP promoted EMT in colorectal cancer cells and that PRELP bind to integrin α5 to activate the integrin α5/FAK/AKT signaling pathway. In conclusion, we demonstrate that PRELP is upregulated in metastatic colorectal cancer, providing a potential prognostic marker and therapeutic target for the clinical management of metastatic colorectal cancer from a biomechanical perspective.

Hierarchical functional differences between gyri and sulci at different scales.

Gyri and sulci are 2 fundamental cortical folding patterns of the human brain. Recent studies have suggested that gyri and sulci may play different functional roles given their structural and functional heterogeneity. However, our understanding of the functional differences between gyri and sulci remains limited due to several factors. Firstly, previous studies have typically focused on either the spatial or temporal domain, neglecting the inherently spatiotemporal nature of brain functions. Secondly, analyses have often been restricted to either local or global scales, leaving the question of hierarchical functional differences unresolved. Lastly, there has been a lack of appropriate analytical tools for interpreting the hierarchical spatiotemporal features that could provide insights into these differences. To overcome these limitations, in this paper, we proposed a novel hierarchical interpretable autoencoder (HIAE) to explore the hierarchical functional difference between gyri and sulci. Central to our approach is its capability to extract hierarchical features via a deep convolutional autoencoder and then to map these features into an embedding vector using a carefully designed feature interpreter. This process transforms the features into interpretable spatiotemporal patterns, which are pivotal in investigating the functional disparities between gyri and sulci. We evaluate the proposed framework on Human Connectome Project task functional magnetic resonance imaging dataset. The experiments demonstrate that the HIAE model can effectively extract and interpret hierarchical spatiotemporal features that are neuroscientifically meaningful. The analyses based on the interpreted features suggest that gyri are more globally activated, whereas sulci are more locally activated, demonstrating a distinct transition in activation patterns as the scale shifts from local to global. Overall, our study provides novel insights into the brain's anatomy-function relationship.

Multiple hydrogen bonding driven supramolecular architectures and their biomedical applications.

Supramolecular chemistry combines the strength of molecular assembly via various molecular interactions. Hydrogen bonding facilitated self-assembly with the advantages of directionality, specificity, reversibility, and strength is a promising approach for constructing advanced supramolecules. There are still some challenges in hydrogen bonding based supramolecular polymers, such as complexity originating from tautomerism of the molecular building modules, the assembly process, and structure versatility of building blocks. In this review, examples are selected to give insights into multiple hydrogen bonding driven emerging supramolecular architectures. We focus on chiral supramolecular assemblies, multiple hydrogen bonding modules as stimuli responsive sources, interpenetrating polymer networks, multiple hydrogen bonding assisted organic frameworks, supramolecular adhesives, energy dissipators, and quantitative analysis of nano-adhesion. The applications in biomedical materials are focused with detailed examples including drug design evolution for myotonic dystrophy, molecular assembly for advanced drug delivery, an indicator displacement strategy for DNA detection, tissue engineering, and self-assembly complexes as gene delivery vectors for gene transfection. In addition, insights into the current challenges and future perspectives of this field to propel the development of multiple hydrogen bonding facilitated supramolecular materials are proposed.

MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.

Osteoarthritis (OA) is a complicated disease that involves apoptosis and mitophagy. MST1 is a pro-apoptotic factor. Hence, decreasing its expression plays an anti-apoptotic effect. This study aims to investigate the protective effect of MST1 inhibition on OA and the underlying processes. Immunofluorescence (IF) was used to detect MST1 expression in cartilage tissue. Western Blot, ELISA and IF were used to analyse the expression of inflammation, extracellular matrix (ECM) degradation, apoptosis and mitophagy-associated proteins. MST1 expression in chondrocytes was inhibited using siRNA and shRNA in vitro and in vivo. Haematoxylin-Eosin, Safranin O-Fast Green and alcian blue staining were used to evaluate the therapeutic effect of inhibiting MST1. This study discovered that the expression of MST1 was higher in OA patients. Inhibition of MST1 reduced inflammation, ECM degradation and apoptosis and enhanced mitophagy in vitro. MST1 inhibition slows OA progression in vivo. Inhibiting MST1 suppressed apoptosis, inflammation and ECM degradation via promoting Parkin-mediated mitophagy and the Nrf2-NF-κB axis. The results suggest that MST1 is a possible therapeutic target for the treatment of osteoarthritis as its inhibition delays the progression of OA through the Nrf2-NF-κB axis and mitophagy.

SOX17 Enhancer Variants Disrupt Transcription Factor Binding And Enhancer Inactivity Drives Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease characterized by remodeling of the pulmonary arteries, increased vascular resistance, and right-sided heart failure. Genome-wide association studies of idiopathic/heritable PAH established novel genetic risk variants, including conserved enhancers upstream of transcription factor (TF) SOX17 containing 2 independent signals. SOX17 is an important TF in embryonic development and in the homeostasis of pulmonary artery endothelial cells (hPAEC) in the adult. Rare pathogenic mutations in SOX17 cause heritable PAH. We hypothesized that PAH risk alleles in an enhancer region impair TF-binding upstream of SOX17, which in turn reduces SOX17 expression and contributes to disturbed endothelial cell function and PAH development. METHODS: CRISPR manipulation and siRNA were used to modulate SOX17 expression. Electromobility shift assays were used to confirm in silico-predicted TF differential binding to the SOX17 variants. Functional assays in hPAECs were used to establish the biological consequences of SOX17 loss. In silico analysis with the connectivity map was used to predict compounds that rescue disturbed SOX17 signaling. Mice with deletion of the SOX17-signal 1 enhancer region (SOX17-4593/enhKO) were phenotyped in response to chronic hypoxia and SU5416/hypoxia. RESULTS: CRISPR inhibition of SOX17-signal 2 and deletion of SOX17-signal 1 specifically decreased SOX17 expression. Electromobility shift assays demonstrated differential binding of hPAEC nuclear proteins to the risk and nonrisk alleles from both SOX17 signals. Candidate TFs HOXA5 and ROR-α were identified through in silico analysis and antibody electromobility shift assays. Analysis of the hPAEC transcriptomes revealed alteration of PAH-relevant pathways on SOX17 silencing, including extracellular matrix regulation. SOX17 silencing in hPAECs resulted in increased apoptosis, proliferation, and disturbance of barrier function. With the use of the connectivity map, compounds were identified that reversed the SOX17-dysfunction transcriptomic signatures in hPAECs. SOX17 enhancer knockout in mice reduced lung SOX17 expression, resulting in more severe pulmonary vascular leak and hypoxia or SU5416/hypoxia-induced pulmonary hypertension. CONCLUSIONS: Common PAH risk variants upstream of the SOX17 promoter reduce endothelial SOX17 expression, at least in part, through differential binding of HOXA5 and ROR-α. Reduced SOX17 expression results in disturbed hPAEC function and PAH. Existing drug compounds can reverse the disturbed SOX17 pulmonary endothelial transcriptomic signature.

Union With Recursive Feature Elimination: A Feature Selection Framework to Improve the Classification Performance of Multicategory Causes of Death in Colorectal Cancer.

Despite the use of machine learning tools, it is challenging to properly model cause-specific deaths in colorectal cancer (CRC) patients and choose appropriate treatments. Here, we propose an interesting feature selection framework, namely union with recursive feature elimination (U-RFE), to select the union feature sets that are crucial in CRC progression-specific mortality using The Cancer Genome Atlas (TCGA) dataset. Based on the union feature sets, we compared the performance of 5 classification algorithms, including logistic regression (LR), support vector machines (SVM), random forest (RF), eXtreme gradient boosting (XGBoost), and Stacking, to identify the best model for classifying 4-category deaths. In the first stage of U-RFE, LR, SVM, and RF were used as base estimators to obtain subsets containing the same number of features but not exactly the same specific features. Union analysis of the subsets was then performed to determine the final union feature set, effectively combining the advantages of different algorithms. We found that the U-RFE framework could improve various models' performance. Stacking outperformed LR, SVM, RF, and XGBoost in most scenarios. When the target feature number of the RFE was set to 50 and the union feature set contained 298 deterministic features, the Stacking model achieved F1_weighted, Recall_weighted, Precision_weighted, Accuracy, and Matthews correlation coefficient of 0.851, 0.864, 0.854, 0.864, and 0.717, respectively. The performance of the minority categories was also significantly improved. Therefore, this recursive feature elimination-based approach of feature selection improves performances of classifying CRC deaths using clinical and omics data or those using other data with high feature redundancy and imbalance.

Neurophysiological, structural, and molecular alterations in the prefrontal and auditory cortices following noise-induced hearing loss.

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices.

Urine Self-Sampling Kit Combined with an Automated Preparation-Sampler Device for Convenient and Reliable Analysis of Arsenic Metabolites by HPLC-ICPMS.

Speciation analysis of arsenic in urine is essential for the studies of arsenic metabolism and biological effects, but the unstable arsenic species represented by MMAIII and DMAIII pose a huge challenge to analytical accuracy. Herein, a novel urine self-sampling (USS) kit combined with an automated preparation-sampler (APS) device is rationally designed and used for convenient analysis of arsenic metabolites by high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). The subject can collect urine into a sampling vial at home and use a homemade syringe to pump argon to displace oxygen in the vial, thereby inhibiting the oxidation of MMAIII and DMAIII. After USS and transportation, the sampling vial is loaded directly onto the APS device, where the urine sample can be automatically mixed with diluent, filtered, and loaded into HPLC-ICPMS for arsenic speciation analysis under anaerobic conditions. For a single sample, the sampling time and the analysis time are <8 and <18 min, respectively. The recoveries of MMAIII and DMAIII in urine over 24 h at 4 °C are 86 and 67%, surpassing the conventional sampling method by 28 and 67%, respectively. When the APS is coupled to HPLC-ICPMS, the detection limits of AsC, iAsIII, MMAIII, DMAV, MMAV, DMAIII, and iAsV are 0.03-0.10 µg L-1 with precisions of <10%. The present method provides a convenient and reliable tool for the storage and analysis of unstable arsenic species in urine and lays the foundation for studying the metabolic and biological effects of methylated trivalent arsenicals.

The role of macrophage polarization in vascular calcification.

Vascular calcification is an important factor in the high morbidity and mortality of Cardiovascular and cerebrovascular diseases. Vascular damage caused by calcification of the intima or media impairs the physiological function of the vascular wall. Inflammation is a central factor in the development of vascular calcification. Macrophages are the main inflammatory cells. Dynamic changes of macrophages with different phenotypes play an important role in the occurrence, progression and stability of calcification. This review focuses on macrophage polarization and the relationship between macrophages of different phenotypes and calcification environment, as well as the mechanism of interaction, it is considered that macrophages can promote vascular calcification by releasing inflammatory mediators and promoting the osteogenic transdifferentiation of smooth muscle cells and so on. In addition, several therapeutic strategies aimed at macrophage polarization for vascular calcification are described, which are of great significance for targeted treatment of vascular calcification.

Engineering Assembly of Plasmonic Virus-Like Gold SERS Nanoprobe Guided by Intelligent Dual-Machine Nanodevice for High-Performance Analysis of Tetracycline.

Accurate detection of trace tetracyclines (TCs) in complex matrices is of great significance for food and environmental safety monitoring. However, traditional recognition and amplification tools exhibit poor specificity and sensitivity. Herein, a novel dual-machine linkage nanodevice (DMLD) is proposed for the first time to achieve high-performance analysis of TC, with a padlock aptamer component as the initiation command center, nucleic acid-encoded multispike virus-like Au nanoparticles (nMVANs) as the signal indicator, and cascade walkers circuit as the processor. The existence of spike vertices and interspike nanogaps in MVANs enables intense electromagnetic near-field focusing, allowing distinct surface-enhanced Raman scattering (SERS) activity. Moreover, through the sequential activation between multistage walker catalytic circuits, the DLMD system converts the limited TC recognition into massive engineering assemblies of SERS probes guided by DNA amplicons, resulting in synergistic enhancement of bulk plasmonic hotspot entities. The continuously guaranteed target recognition and progressively promoted signal enhancement ensure highly specific amplification analysis of TC, with a detection limit as low as 7.94 × 10-16 g mL-1. Furthermore, the reliable recoveries in real samples confirm the practicability of the proposed sensing platform, highlighting the enormous potential of intelligent nanomachines for analyzing the trace hazards in the environment and food.

Structure and dynamics of microbial communities associated with the resurrection plant Boea hygrometrica in response to drought stress.

MAIN CONCLUSION: The resurrection plant Boea hygrometrica selectively recruits and assembles drought-specific microbial communities across the plant-soil compartments, which may benefit plant growth and fitness under extreme drought conditions. Plant-associated microbes are essential for facilitating plant growth and fitness under drought stress. The resurrection plant Boea hygrometrica in natural habitats with seasonal rainfall can survive rapid desiccation, yet their interaction with microbiomes under drought conditions remains unexplored. This study examined the bacterial and fungal microbiome structure and drought response across plant-soil compartments of B. hygrometrica by high-throughput amplicon sequencing of 16S rRNA gene and internal transcribed spacer. Our results demonstrated that the diversity, composition, and functional profile of the microbial community varied considerably across the plant-soil compartments and were strongly affected by drought stress. Bacterial and fungal diversity was significantly reduced from soil to endosphere and belowground to aboveground compartments. The compartment-specific enrichment of the dominant bacteria phylum Cyanobacteriota and genus Methylorubrum in leaf endosphere, genera Pseudonocardia in rhizosphere soil and Actinoplanes in root endosphere, and fungal phylum Ascomycota in the aboveground compartments and genera Knufia in root endosphere and Cladosporium in leaf endosphere composed part of the core microbiota with corresponding enrichment of beneficial functions for plant growth and fitness. Moreover, the recruitment of dominant microbial genera Sphingosinicella and Plectosphaerella, Ceratobasidiaceae mycorrhizal fungi, and numerous plant growth-promoting bacteria involving nutrient supply and auxin regulation was observed in desiccated B. hygrometrica plants. Our results suggest that the stable assembled drought-specific microbial community of B. hygrometrica may contribute to plant survival under extreme environments and provide valuable microbial resources for the microbe-mediated drought tolerance enhancement in crops.

Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor.

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen (1O2) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1O2. This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.