Adoption of the 2A Ribosomal Skip Principle to Track Assembled Virions of Pepper Mild Mottle Virus in Nicotiana benthamiana.

The coat protein (CP) is an important structural protein that plays many functional roles during the viral cycle. In this study, the CP of pepper mild mottle virus (PMMoV) was genetically fused to GFP using the foot-and-mouth disease virus peptide 2A linker peptide and the construct (PMMoV-GFP2A) was shown to be infectious. The systemic spread of the virus was monitored by its fluorescence in infected plants. Electron microscopy and immunocolloidal gold labelling confirmed that PMMoV-GFP2A forms rod-shaped particles on which GFP is displayed. Studies of tissue ultrastructure and virion self-assembly confirmed that PMMoV-GFP2A could be used to monitor the real-time dynamic changes of CP location during virus infection. Aggregations of GFP-tagged virions appeared as fluorescent plaques in confocal laser microscopy. Altogether, PMMoV-GFP2A is a useful tool for studying the spatial and temporal changes of PMMoV CP during viral infection.

Nerve Guide Conduits Integrated with Fisetin-Loaded Chitosan Hydrogels for Reducing Oxidative Stress, Inflammation, and Nerve Regeneration.

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.

EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3.

OBJECTIVE: Erythropoietin (EPO) known as an erythrocyte-stimulating factor is increased in patients with rheumatoid arthritis (RA). Nevertheless, the function of EPO in the process of RA and relative mechanism needs to be further clarified. METHODS: The level of EPO in serum and synovial fluid from patients with RA and healthy controls was determined by . Collagen-induced arthritis (CIA) mice were constructed to confirm the role of EPO on RA pathogenesis. Differentially expressed genes (DEGs) of EPO-treated fibroblast-like synoviocyte (FLS) were screened by transcriptome sequencing. The transcription factor of neuraminidase 3 (NEU3) of DEGs was verified by double luciferase reporting experiment, DNA pulldown, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR (qPCR) assay. RESULTS: The overexpression of EPO was confirmed in patients with RA, which was positively associated with Disease Activity Score 28-joint count. Additionally, EPO intervention could significantly aggravate the joint destruction in CIA models. The upregulation of NEU3 was screened and verified by transcriptome sequencing and qPCR in EPO-treated FLS, and signal transducer and activator of transcription 5 was screened and verified to be the specific transcription factor of NEU3. EPO upregulates NEU3 expression via activating the Janus kinase 2 (JAK2)-STAT5 signalling pathway through its receptor EPOR, thereby to promote the desialylation through enhancing the migration and invasion ability of FLS, which is verified by JAK2 inhibitor and NEU3 inhibitor. CONCLUSION: EPO, as a proinflammatory factor, accelerates the process of RA through transcriptional upregulation of the expression of NEU3 by JAK2/STAT5 pathway.

CCCTC-binding factor: the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

Characteristics of Amorphophallus konjac as indicated by its genome.

Amorphophallus konjac, belonging to the genus Amorphophallus of the Araceae family, is an economically important crop widely used in health products and biomaterials. In the present work, we performed the whole-genome assembly of A. konjac based on the NovaSeq platform sequence data. The final genome assembly was 4.58 Gb with a scaffold N50 of 3212 bp. The genome includes 39,421 protein-coding genes, and 71.75% of the assemblies were repetitive sequences. Comparative genomic analysis showed 1647 gene families have expanded and 2685 contracted in the A. konjac genome. Likewise, genome evolution analysis indicated that A. konjac underwent whole-genome duplication, possibly contributing to the expansion of certain gene families. Furthermore, we identified many candidate genes involved in the tuber formation and development, cellulose and lignification synthesis. The genome of A. konjac obtained in this work provides a valuable resource for the further study of the genetics, genomics, and breeding of this economically important crop, as well as for evolutionary studies of Araceae family.

First Report of Clover yellow vein virus Infecting Senna septemtrionalis (Arsenic bush).

Clover yellow vein virus (ClYVV) is a member of the genus Potyvirus, family Potyviridae and was reported to infect many plant species, such as Ammi majus L., Phaseolus vulgaris L., Vicia faba L., Lens culinaris L., Borago officinalis L., Cicer arietinum L., Gladiolous gandavensis L., Glycine max L., Trifolium repens L., and Dendrobium sp. (Irey et al. 2006; Ortiz et al. 2009; Park et al. 2014; Yoon et al. 2022). Senna septemtrionalis (Viv.) H.S.Irwin & Barneby (arsenic bush), a species in the subfamily Caesalpinioideae, is widely distributed in tropical and subtropical regions (Datiles et al. 2022). In June 2021, virus-like symptoms of mosaic, chlorosis, and leaf-curling were observed in arsenic bush in Kunming, Yunnan province, China. Symptomatic leaves were collected from four arsenic bush (SS1-4), and asymptomatic leaves were collected from 3 additional arsenic bush plants (SS5-7) (eXtra S1). To identify the putative causal virus, sap of symptomatic leaves (SS1) was stained with 1 % phosphotungstic acid and observed under a transmission electron microscope (TEM). Potyvirus-like particles (about 750-800 nm  13 nm) were observed from the sample (eXtra S1). Total RNA was extracted from sample SS1 using TRIzol Reagent (Invitrogen, USA) and subjected to the Illumina NovaSeq platform for RNA-Seq. After trimming and quality control of raw data, 24,125,963 high-quality clean reads were assembled into 72,835 Unigenes using Trinity software. BLAST searches indicated that the nucleotide sequence of Unigene c29731 (10,893 nt) and its deduced amino acid sequence shared 82.62% to 96.45% and 92.60% to 99.19% identity with several ClYVV isolates, respectively. Unigene c29731 had the highest coverage ratio (88%) and the highest nucleotide sequence identity (96.45%) with ClYVV isolate IA-2016 (GenBank accession No. MK292120.1). The complete genome of ClYVV SS1 isolate (ClYVV-SS, GenBank accession No. OP868578) was determined using RT-PCR and 5' and 3' rapid amplification of cDNA ends (RACE) (Chen et al. 2001). A total of 224,936 out of 24,125,963 reads were mapped to the ClYVV-SS1 genome, yielding an average depth of coverage of 3,056.823 (min=1, max=7,859) at nucleotides from 1 to 9,324 of ClYVV genome (eXtra S2). BLASTN results indicated that the complete genome of ClYVV-SS1 shared 96.45% nucleotide sequence identity and 99% coverage ratio with ClYVV isolate IA-2016 genome. Phylogenetic analysis showed that ClYVV-SS1 and other ClYVV isolates clustered together (eXtra S2). RT-PCR was performed on samples (SS2-7) using a pair of primers of the coat protein gene (5'- TCCGACAAAGATAAGTTGAATGCTGGTG-3' and 5'-GAATCGTGCTCCAGCAATGTGA-3') designed from multiple sequences alignment (MSA). Using SS1 sample as positive control, amplicons of ~813 bp were obtained from three symptomatic samples (SS2-4) but not the asymptomatic ones (SS5-7). A total of 17 of 20 arsenic bushes developed symptoms of mosaic and leaf-curling approximately two weeks after mechanical inoculation with arsenic bush (SS1) sap, with 10 uninoculated plants used as control (eXtra S1). RT-PCR was performed for all tested plants. 17 symptomatic arsenic bushes tested positive for ClYVV, while all other samples tested negative. This confirmed that the symptomatic arsenic bushes were infected with ClYVV. To our knowledge, this is the first report of ClYVV infecting arsenic bush.

Chlorogenic acid releasing microspheres enhanced electrospun conduits to promote peripheral nerve regeneration.

Chlorogenic acid (CGA) has been confirmed as a polyphenol, and existing research has suggested the high bioactivity of CGA for therapeutic effects on a wide variety of diseases. Despite the existing reports of anti-inflammatory, antioxidant, and neuroprotective effects of CGA, the role and mechanism of CGA in facilitating the regeneration of peripheral nerve defects have been rarely investigated. Herein, a biodegradable polycaprolactone (PCL) conduit with embedded CGA-releasing GelMA microspheres (CGM/PCL) was successfully prepared and used for repairing a rate model with sciatic nerve defects. CGM and CGM/PCL conduits displayed high in vitro biocompatibility and can support the growth of cells for nerve regeneration. Furthermore, CGM/PCL conduits displayed high performance which is close to that of autologous nerve grafts in promoting in vivo PNI regeneration, compared with PCL conduits. The sciatic nerve functional index analysis, electrophysiological examination, and immunological analysis performed to evaluate the functional recovery of the injurious sciatic nerve of rats have indeed proved the favorable effects of CGM/PCL conduits. The result of this study not only aimed to explore CGA's contribution to nerve regeneration but also provided a new strategy for designing and preparing functional NGCs for PNI treatment.

A fully human monoclonal antibody targeting Semaphorin 5A alleviates the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common chronic autoimmune disease worldwide. Although progress has been made in RA treatment in recent decades, remission cannot be effectively achieved for a considerable proportion of RA patients. Thus, novel potential targets for therapeutic strategies are needed. Semaphorin 5A (SEMA5A) plays a pivotal role in RA progression by facilitating pannus formation, and it is a promising therapeutic target. In this study, we sought to develop an antibody treatment strategy targeting SEMA5A and evaluate its therapeutic effect using a collagen-induced arthritis (CIA) model. We generated SYD12-12, a fully human SEMA5A blocking antibody, through phage display technology. SYD12-12 intervention effectively inhibited angiogenesis and aggressive phenotypes of RA synoviocytes in vitro and dose-dependently inhibited synovial hyperplasia, pannus formation, bone destruction in CIA mice. Notably, SYD12-12 also improved the Treg/Th17 imbalance in CIA mice. We confirmed through immunofluorescence and molecular docking that SYD12-12 integrated with the unique TSP-1 domain of SEMA5A. In conclusion, we developed and characterized a fully human SEMA5A-blocking antibody for the first time. SYD12-12 effectively alleviated disease progression in CIA mice by inhibiting pannus formation and improving the Treg/Th17 imbalance, demonstrating its potential for the RA treatment.

Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy.

Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.

[Retracted] Silencing cyclin­dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 1C were strikingly similar to data appearing in different form in another article written by different authors at different research institutes [Chen Y, Guo Y, Yang H, Shi G, Xu G, Shi J, Yin N and Chen D: TRIM66 overexpression contributes to osteosarcoma carcinogenesis and indicates poor survival outcome. Oncotarget 6: 23708­23719, 2015]. Moreover, a pair of data panels showing the results from cell­cycle experiments purportedly performed under different experimental conditions in Fig. 4A appeared to be strikingly similar. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 1523­1530, 2016; DOI: 10.3892/mmr.2016.5401].

Inhibition of autophagy and RIP1/RIP3/MLKL-mediated necroptosis by edaravone attenuates blood spinal cord barrier disruption following spinal cord injury.

The disruption of the blood spinal cord barrier (BSCB) after spinal cord injury (SCI) can trigger secondary tissue damage. Edaravone is likely to protect the BSCB as a free radical scavenger, whereas it has been rarely reported thus far. In this study, the protective effect of edaravone was investigated with the use of compression spinal cord injured rats and human brain microvascular endothelial cells (HBMECs) injury. As indicated by the result of this study, edaravone treatment facilitated functional recovery after rats were subjected to SCI, ameliorated the vascular damage, and up-regulated the expression of BSCB-associated proteins. In vitro results, edaravone improved HBMECs viability, restored intercellular junctions, and promoted cellular angiogenic activities. It is noteworthy that autophagy was activated and RIP1/RIP3/MLKL phosphorylation was notably up-regulated. However, edaravone treatment exhibited the capability of mitigating above-mentioned tendency in vivo and in vitro. Moreover, rapamycin (Rapa) treatment deteriorated the protective effect of edaravone while aggravating the phosphorylation of RIP1/RIP3/MLKL expression. In the model of necrotic activator-induced HBMECs, autophagic expression was increased, whereas edaravone prevented autophagy and phosphorylation of RIP1/RIP3/MLKL. In general, our results suggested that edaravone is capable of reducing the destruction of BSCB and promoting functional recovery after SCI. The possible underlying mechanism is that edaravone is capable of protecting angiogenic activity and improving autophagy and the phosphorylation of RIP1/RIP3/MLKL, as well as their mutual deterioration. Accordingly, edaravone can be a favorable option for the treatment of SCI.

Erythropoietin-mediated IL-17 F attenuates sepsis-induced gut microbiota dysbiosis and barrier dysfunction.

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.

Agomir miRNA-150-5p alleviates pristane-induced lupus by suppressing myeloid dendritic cells activation and inflammation via TREM-1 axis.

OBJECTIVE: Triggering receptors expressed on myeloid cells-1 (TREM-1) has been shown to participate in inflammatory autoimmune diseases. Nevertheless, the detailed underlying mechanisms and therapeutic benefits by targeting TREM-1 remain elusive, especially in myeloid dendritic cells (mDCs) and systemic lupus erythematosus (SLE). Disorders of epigenetic processes including non-coding RNAs give rise to SLE, resulting in complicated syndromes. Here, we aim to address this issue and explore the miRNA to inhibit the activation of mDCs and alleviate the progress of SLE by targeting TREM-1 signal axis. METHODS: Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between patients with SLE and healthy individuals by four mRNA microarray datasets from Gene Expression Omnibus (GEO). Then we identified the expression of TREM-1 and its soluble form (sTREM-1) in clinical samples by ELISA, quantitative real-time PCR and Western blot. Phenotypic and functional changes of mDCs elicited by TREM-1 agonist were determined. Three databases of miRNAs target prediction and a dual-luciferase reporter assay were used to screen and verify miRNAs that can directly inhibit TREM-1 expression in vitro. Moreover, pristane-induced lupus mice were injected with miR-150-5p agomir to evaluate the effects of miR-150-5p on mDCs in lymphatic organs and disease activity in vivo. RESULTS: We screened TREM-1 as one of the hub genes closely correlated with the progression of SLE and identified sTREM-1 in serum as a valuable diagnostic biomarker for SLE. Moreover, activation of TREM-1 by its agonist promoted activation and chemotaxis of mDCs and increased the production of inflammatory cytokines and chemokines, showing higher expression of IL-6, TNF-α, and MCP-1. We showed that lupus mice displayed a unique miRNA signature in spleen, among which miR-150 was the most significantly expressed miRNA that targeting TREM-1 compared with wild type group. Transfection of miRNA-150-5p mimics directly suppressed the expression of TREM-1 by binding to its 3' UTR. Our in vivo experiments first indicated that administration of miR-150-5p agomir effectively ameliorated lupus symptoms. Intriguingly, miR-150 inhibited the over activation of mDCs through TREM-1 signal pathway in lymphatic organs and renal tissues. CONCLUSIONS: TREM-1 represents a potentially novel therapeutic target and we identify miR-150-5p as one of the mechanisms to alleviate lupus disease, which is attributable for inhibiting mDCs activation through TREM-1 signaling pathway.

The Process and Mechanism of Preparing Nanoporous Silicon: Helium Ion Implantation.

Ion implantation is an effective way to control performance in semiconductor technology. In this paper, the fabrication of 1~5 nm porous silicon by helium ion implantation was systemically studied, and the growth mechanism and regulation mechanism of helium bubbles in monocrystalline silicon at low temperatures were revealed. In this work, 100 keV He ions (1~7.5 × 1016 ions/cm2) were implanted into monocrystalline silicon at 115 °C~220 °C. There were three distinct stages in the growth of helium bubbles, showing different mechanisms of helium bubble formation. The minimum average diameter of a helium bubble is approximately 2.3 nm, and the maximum number density of the helium bubble is 4.2 × 1023 m-3 at 175 °C. The porous structure may not be obtained at injection temperatures below 115 °C or injection doses below 2.5 × 1016 ions/cm2. In the process, both the ion implantation temperature and ion implantation dose affect the growth of helium bubbles in monocrystalline silicon. Our findings suggest an effective approach to the fabrication of 1~5 nm nanoporous silicon, challenging the classic view of the relationship between process temperature or dose and pore size of porous silicon, and some new theories are summarized.

A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.

BACKGROUND: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. RESULTS: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. CONCLUSION: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the prognosis of patients is poor due to chemotherapeutic resistance. Interestingly, patients with HNSCC induced by human papillomavirus (HPV) infection are more sensitive to chemotherapy and display a better prognosis than HPV-negative patients. The biological relevance of HPV infection and the mechanism underlying chemosensitivity to cisplatin remain unknown. Herein, SERPINB3 is identified as an important target for regulation of cisplatin sensitivity by HPV-E6/E7 in HNSCC. Downregulation of SERPINB3 inhibits cisplatin-induced DNA damage repair and enhances the cytotoxicity of cisplatin. In detail, decreasing SERPINB3 expression reduces the USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia pathway, thereby interfering with cisplatin-induced DNA interstrand crosslinks repair and further contributing to HNSCC cell apoptosis. To translate this finding, pH-responsive nanoparticles are used to deliver SERPINB3 small interfering RNA in combination with cisplatin, and this treatment successfully reverses cisplatin chemotherapeutic resistance in a patient-derived xenograft model from HPV-negative HNSCC. Taken together, these findings suggest that targeting SERPINB3 based on HPV-positive HNSCC is a potential strategy to overcome cisplatin resistance in HPV-negative HNSCC and improves the prognosis of this disease.

Correction: PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration.

Correction for 'PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration' by Xue-Han Jin et al., J. Mater. Chem. B, 2022, https://doi.org/10.1039/D2TB01624A.

PCL NGCs integrated with urolithin-A-loaded hydrogels for nerve regeneration.

Inflammation and oxidative stress are among the leading causes of poor prognosis after peripheral nerve injury (PNI). Urolithin-A (UA), an intermediate product produced by the catabolism of ellagitannins in the gastrointestinal tract, has anti-inflammatory, antioxidant, and immunomodulatory properties for inflammation, oxidative damage, and aging-related diseases. Hence, we prepared UA-loaded hydrogels and embedded them in the lumen of PCL nerve guide conduits (NGCs). The hydrogels continuously released appropriate doses of UA into the microenvironment. Based on in vitro studies, UA facilitates cell proliferation and reduces oxidative damage. Besides, the experimental evaluation revealed good biocompatibility of the materials involved. We implanted NGCs into rat models to bridge the sciatic nerve defects in an in vivo study. The sciatic functional index of the PCL/collagen/UA group was comparable to that of the autograft group. Additionally, the consequences of electrophysiological, gastrocnemius muscle and nerve histology assessment of the PCL/collagen/UA group were better than those in the PCL and PCL/collagen groups and close to those in the autograft group. In this study, UA sustained release via the PCL/collagen/UA NGC was found to be an effective alternative treatment for PNI, validating our hypothesis that UA could promote regeneration of nerve tissue.

Performance and microbial community of MBBRs under three maintenance strategies for intermittent stormwater treatment.

Maintaining microbial activities is a critical problem for biological treatment processes of stormwater runoff because of its intermittent nature. In this study, the suitability of the moving bed biofilm reactor (MBBR) was assessed for stormwater treatment by long-term dry - rainy alternation operation. Three strategies to maintain microbial activities during the dry period, including keeping idle (MBBRI), introducing river water throughout the period (MBBRC), and ahead of a rainy day (MBBRM), were investigated. COD and NH4+-N removal efficiencies declined linearly from 94.2 % and 94.7 % to 51.7 % and 64.6 %, respectively, after the 61-day operation with microbial activity and biomass decreased. Introducing river water adversely affected the process performance as MBBRC presented the highest declining rates of COD and NH4+-N removal efficiencies. Most genera in MBBRs decayed and their microbial communities developed towards individualization, especially in MBBRM because of its highest environmental variability. Keeping idle slightly alleviated the performance decline and formed a more stable microbial community structure. However, significantly deteriorating performance in all MBBRs after the long-term operation indicated that MBBRs were unsuitable for treating stormwater independently of intermittent nature.