Pyrenetetrasulfonate-grafted 2D ultrathin metal-organic layer as new electrochemiluminescence emitters for ultrasensitive microRNA-21 assay.

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates. The main reason was that the distance between pyrene rings was greatly expanded after the PyTS grafting on the Zr6 clusters of Zr-BTB-MOL, which overcame the aggregation-caused quenching (ACQ) effect of PyTS and thus enhanced the ECL emission. Meanwhile, the porous nanosheet structure of PyTS-Zr-BTB-MOL could distinctly increase the exposure of PyTS luminophores and shorten the diffusion paths of coreactants and electrons/ions, which effectively promoted the electrochemical excitation of more PyTS luminophores and thus achieved a further ECL enhancement. In light of the remarkable ECL property of PyTS-Zr-BTB-MOL, it was employed as an ECL indicator to build a novel high-sensitivity ECL biosensor for microRNA-21 determination, possessing a satisfactory response range (100 aM to 100 pM) and an ultralow detection limit (10.4 aM). Overall, this work demonstrated that using MOLs to coordinatively graft the PAH derivative luminophores to eliminate the ACQ effect and increase the utilization rate of the luminophores is a promising and efficient strategy to develop high-performance Ru-complex-free ECL materials for assembling ultrasensitive ECL biosensing platforms.

A transient transcriptional activation governs unpolarized-to-polarized morphogenesis during embryo implantation.

During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.

Corrigendum: An in-cluster Sfp-type phosphopantetheinyl transferase instead of the holo-ACP synthase activates the granaticin biosynthesis under natural physiological conditions.

[This corrects the article DOI: 10.3389/fchem.2022.1112362.].

Bacterial exonuclease III expands its enzymatic activities on single-stranded DNA.

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

Comparison of non-volatile compounds of Penaeus vannemei with different drying treatments via multidimensional infrared spectroscopy.

To analyze the effect of various drying treatments (microwave drying (MD), hot air drying (HAD), vacuum drying (VD), and vacuum freeze drying (VFD)) on taste compounds in Penaeus vannamei, relevant indicators such as free amino acids, 5'-nucleotides, and organic acids were performed. Multidimensional infrared spectroscopy (MM-IR) results found that there were notable variations in taste properties of P. vannamei. There were 18 autocorrelation peaks in 3400-900 cm-1 were screened using second-derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR). Variations in functional groups were the major contributors to taste profiles. The TAV of glutamic acid (Glu), guanine (GMP), and inosinemonphosphate (IMP) were greater than one and had notable impacts on taste profiles. VD had the highest equivalent umami value, followed by VFD, HAD, and MD. This study may provide a theoretical guide for the production of dried P. vannamei products on an industrial scale.

Polymer colloidal motors with photodynamic-regulated propulsion.

Artificial colloidal motors capable of converting various external energy into mechanical motion, have emerged as attractive photosensitizer (PS) nanocarriers with good deliverability for photodynamic therapy. However, photoactivated 3O2-to-1O2 transformation as the most crucial energy transfer of the photodynamic process itself is still challenging to convert into autonomous transport. Herein, we report on PS-loaded thiophane-containing semiconducting conjugated polymer (SCP)-based polymer colloidal motors with asymmetric geometry for photodynamic-regulated propulsion in the liquid. The asymmetrical presence of the SCP phases within the colloidal motors would lead to significant differences in the 3O2-to-1O2 transformation and 1O2 release manners between asymmetrical polymer phases, spontaneously creating asymmetrical osmotic pressure gradients across the nanoparticles for powering the self-propelled motion under photodynamic regulation. This photoactivated energy-converting behavior can be also combined with the photothermal conversion of the SCP phases to create two energy gradients exerting diffusiophoretic/thermophoretic force on the colloidal motors for achieving multimode synergistic propulsion. This unique motile feature endows the light-driven PS nanocarriers with good permeability against various physiological barriers in the tumor microenvironment for enhancing antitumor efficacy, showing great potential in phototherapy.

Efficient pyramid channel attention network for pathological myopia recognition with pretraining-and-finetuning.

Pathological myopia (PM) is the leading ocular disease for impaired vision worldwide. Clinically, the characteristics of pathology distribution in PM are global-local on the fundus image, which plays a significant role in assisting clinicians in diagnosing PM. However, most existing deep neural networks focused on designing complex architectures but rarely explored the pathology distribution prior of PM. To tackle this issue, we propose an efficient pyramid channel attention (EPCA) module, which fully leverages the potential of the clinical pathology prior of PM with pyramid pooling and multi-scale context fusion. Then, we construct EPCA-Net for automatic PM recognition based on fundus images by stacking a sequence of EPCA modules. Moreover, motivated by the recent pretraining-and-finetuning paradigm, we attempt to adapt pre-trained natural image models for PM recognition by freezing them and treating the EPCA and other attention modules as adapters. In addition, we construct a PM recognition benchmark termed PM-fundus by collecting fundus images of PM from publicly available datasets. The comprehensive experiments demonstrate the superiority of EPCA-Net over state-of-the-art methods in the PM recognition task. For example, EPCA-Net achieves 97.56% accuracy and outperforms ViT by 2.85% accuracy on the PM-fundus dataset. The results also show that our method based on the pretraining-and-finetuning paradigm achieves competitive performance through comparisons to part of previous methods based on traditional fine-tuning paradigm with fewer tunable parameters, which has the potential to leverage more natural image foundation models to address the PM recognition task in limited medical data regime.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

CALU promotes lung adenocarcinoma progression by enhancing cell proliferation, migration and invasion.

BACKGROUND: Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms. METHODS: 5-ethynyl-2'-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells. RESULTS: The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells. CONCLUSIONS: The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.

Transcriptome analysis of Vero cells infected with attenuated vaccine strain CDV-QN-1.

To better understand the interaction between attenuated vaccines and host antiviral responses, we used bioinformatics and public transcriptomics data to analyze the immune response mechanisms of host cells after canine distemper virus (CDV) infection in Vero cells and screened for potential key effector factors. In this study, CDV-QN-1 infect with Vero cells at an MOI of 0.5, and total RNA was extracted from the cells 24 h later and reverse transcribed into cDNA. Transcriptome high-throughput sequencing perform using Illumina. The results showed that 438 differentially expressed genes were screened, of which 409 were significantly up-regulated and 29 were significantly down-regulated. Eight differentially expressed genes were randomly selected for RT-qPCR validation, and the change trend was consistent with the transcriptomics data. GO and KEGG analysis of differentially expressed genes revealed that most of the differentially expressed genes in CDV-QN-1 infection in the early stage were related to immune response and antiviral activity. The enriched signaling pathways mainly included the interaction between cytokines and cytokine receptors, the NF-kappa B signaling pathway, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway. This study provides a foundation for further exploring the pathogenesis of CDV and the innate immune response of host cells in the early stage of infection.

Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Maintenance therapy with anlotinib after induction therapy with platinum-based chemotherapy for advanced non-small-cell lung cancer: A pooled analysis of 2 single-arm trials.

BACKGROUND: Maintenance therapy could significantly improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. Anlotinib is effective, tolerable, and convenient in administration as a third-line treatment for NSCLC. This study aimed to evaluate the efficacy and safety of maintenance therapy with anlotinib after platinum-based induction chemotherapy for patients with advanced NSCLC. METHODS: This pooled analysis of 2 multicenter, open-label, single-arm, phase 2 clinical trials (ALTER-L014 and ALTER-L011) enrolled patients with locally advanced or metastatic NSCLC and without known sensitive mutations in China between September 2018 and January 2021. The primary outcome was progression-free survival. The secondary outcomes were objective response rate, disease control rate, overall survival, and safety. RESULTS: The data of 23 patients were pooled, with 15 from ALTER-L014 and 8 from ALTER-L011. At the cutoff date of June 13, 2021, the median progression-free survival since the start of maintenance therapy was 5.95 (95% confidence interval, 4.30-8.80) months. Nineteen patients had stable disease, 1 had a partial response and 3 had progressive disease. The objective response rate was 4.35%, while disease control rate was 86.96%. The median overall survival of the patients since the start of maintenance therapy was 18.60 (95% confidence interval, 6.87-22.80) months. The incidence of adverse events of grade ≥ 3 was 21.7%. CONCLUSION: Anlotinib might offer a new option for maintenance treatment in patients with locally advanced or metastatic NSCLC without known sensitive mutations after standard first-line platinum-based chemotherapy.

The key role of unique crystalline property in the hydrolytic degradation process of microcrystalline cellulose-reinforced stereo-complexed poly(lactic acid) composites.

Stereo-complexed poly(lactic acid) (SC-PLA) has unique stereo-complexed crystallites (SC) and homogeneous crystallites (HC), but the effect of this special crystalline property on the hydrolytic degradation of SC-PLA has not been researched. In this study, the hygrothermal aging behaviour of injection-molded SC-PLA and SC-PLA/microcrystalline cellulose (MCC) composites at different temperatures (25 °C and 60 °C) was investigated from micro- and macroscopic perspectives. The results demonstrated that the hydrolysis of SC-PLA was sequentially dominated by the amorphous region, the homogeneous crystalline region, the stereo-complexed crystalline region (three stages). The hydrolytic degradation of SC-PLA only completed the first stage after 4 weeks aging at 25 °C, while it was in the third stage after 4 weeks aging at 60 °C. On this basis, the accelerating effect of 10 wt% MCC on the hydrolysis process of SC-PLA at different stages was investigated. It was found that MCC shortened the hydrolysis time in the stereo-complexed crystalline region by reducing the rearrangement of amorphous structure to form SC and causing cracks and interfacial deterioration by water absorption-swelling-degradation. In addition, the thermal properties and impact strength of SC-PLA and SC-PLA/MCC composites decreased dramatically due to rapid hydrolytic degradation at 60 °C. Overall, the results of this study can provide theoretical basis for the application of SC-PLA and SC-PLA/MCC composites in hygrothermal environment.

The interplay of psychological resilience and adolescent mobile phone addiction in Henan province, China: insights from latent class analysis.

Background: The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5. Methods: We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751). Results: The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction. Conclusion: This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

O-GlcNAc signaling: implications for stress-induced adaptive response pathway in the tumor microenvironment.

The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis.

Cancer cell extravasation requires iplectin-mediated delivery of MT1-MMP at invadopodia.

BACKGROUND: Invadopodia facilitate cancer cell extravasation, but the molecular mechanism whereby invadopodia-specific proteases such as MT1-MMP are called to invadopodia is unclear. METHODS: Mass spectrometry and immunoprecipitation were used to identify interactors of MT1-MMP in metastatic breast cancer cells. After identification, siRNA and small molecule inhibitors were used to assess the effect these interactors had on cellular invasiveness. The chicken embryo chorioallantoic membrane (CAM) model was used to assess extravasation and invadopodia formation in vivo. RESULTS: In metastatic breast cancer cells, MT1-MMP was found to associate with plectin, a cytolinker and scaffolding protein. Complex formation between plectin and MT1-MMP launches invadopodia formation, a subtype we termed iplectin (i = invadopodial). iPlectin delivers MT1-MMP to invadopodia and is indispensable for regulating cell surface levels of the enzyme. Genetic depletion of plectin with siRNA reduced invadopodia formation and cell invasion in vitro. In vivo extravasation efficiency assays and intravital imaging revealed iplectin to be a key contributor to invadopodia ultrastructure and essential for extravasation. Pharmacologic inhibition of plectin using the small molecule Plecstatin-1 (PST-1) abrogated MT1-MMP delivery to invadopodia and extravasation efficiency. CONCLUSIONS: Anti-metastasis therapeutic approaches that target invadopodia are possible by disrupting interactions between MT1-MMP and iplectin. CLINICAL TRIAL REGISTRATION NUMBER: NCT04608357.

Influence of humic acid on the p-tert-Butylphenol removal efficiency by Spirodela polyrhiza-Tas13 association.

Plant-microbe remediation technique is considered as a promising technology in removal of organic pollutants and its remediation efficiency is largely affected by a variety of surrounding environmental factors. Humic acid (HA) is the complex organic substance ubiquitous in environment, which characterized by its surfactant-like micelle microstructure and various reaction activity. In our study, a plant-microbe association with high p-tert-Butylphenol (PTBP) degradation potential constructed by Spirodela polyrhiza and Sphingobium phenoxybenzoativorans Tas13 has been used, and the influence of HA on the PTBP degradation efficiency of S. polyrhiza-Tas13 association was investigated. The result showed that the presence of HA greatly improved PTBP removal efficiency of S. polyrhiza-Tas13. The reason accounted for this may be due to the presence of HA promoted bacterial cell propagation, altered bacterial cell wall permeability, increased catechol 2,3-dioxygenase (C23O) enzyme activity of strain Tas13, rather than increasing the colonization ability of strain Tas13 on to the root surface. This study will greatly facilitate the application of aquatic plant-microbe association in environmental remediation.