Structural and Na-ion diffusion behavior of O3/P3/P2-type NaNi1/3Mn1/3Fe1/3O2 cathode for Na-ion batteries from first-principles study.

A layered sodium-ion battery cathode, O3/P3/P2-type NaNi1/3Mn1/3Fe1/3O2, has been systematically investigated by first-principles density functional theory to explore the detailed structural and Na-ion diffusion behavior during desodiation. Our results suggest that the (NaO6) spacing is greatest in the P3 phase and lowest in the O3 phase, with the P2 phase exhibiting intermediate spacing. During desodiation, the intermediate stages have a greater (NaO6) spacing than the initial and final stages. The great (NaO6) spacing facilitates the formation of the P3 phase, resulting in the structural evolution of NaxNi1/3Mn1/3Fe1/3O2 from the O3 to the P3 phase at x ≈ 0.59, finally reaching the O3 structure again at x ≈ 0.12. The electronic structure clearly proves that both Ni and Fe are active in O3/P3/P2-type NaxNi1/3Mn1/3Fe1/3O2. Ni2+ is oxidized to Ni3+ as Na content decreases from x = 1 to x = 0.66, then further oxidized to Ni4+ at x = 0.33, and finally, Fe3+ → Fe4+ oxidation occurs at x = 0. In the Na ion diffusion behavior, the order of the barrier is O3 (0.82 eV) > P2 (0.53 eV) > P3 (0.35 eV) at the initial stage, whereas it is O3 (0.53 eV) > P3 (0.21 eV) > P2 (0.16 eV) at a highly desodiated stage. The former can be traced back to the (NaO6) spacing, but the latter is related to the different Na sites. Our results thus provide a factor of the structural evolution and Na ion diffusion barrier by considering (NaO6) width and Na site changes during desodiation.

Vv-circSIZ1 mediated by pre-mRNA processing machinery contributes to salt tolerance.

CircRNAs exist widely in plants, but the regulatory mechanisms for the biogenesis and function of plant circRNAs remain largely unknown. Using extensive mutagenesis of expression plasmids and genetic transformation methods, we analyzed the biogenesis and anti-salt functions of a new grape circRNA Vv-circSIZ1. We identified Vv-circSIZ1 that is mainly expressed in the cytoplasm of xylem. CircSIZ1 is species-specific, and genomic circSIZ1-forming region of seven tested species could be backspliced in Nicotiana benthamiana, but not in Arabidopsis. The retention length of Vv-circSIZ1 flanking introns was significantly positively correlated with its generation efficiency. The precise splicing of Vv-circSIZ1 does not depend on its mature exon sequence or internal intron sequences, but on the AG/GT splicing signal sites and branch site of the flanking introns. The spliceosome activity was inversely proportional to the expression level of Vv-circSIZ1. Furthermore, RNA-binding proteins can regulate the expression of Vv-circSIZ1. The overexpression of Vv-circSIZ1 improved salt tolerance of grape and N. benthamiana. Additionally, Vv-circSIZ1 could relieve the repressive effect of VvmiR3631 on its target VvVHAc1. Vv-circSIZ1 also promoted transcription of its parental gene. Overall, these results broaden our understanding of circRNAs in plants.

Advances of hydrogel combined with stem cells in promoting chronic wound healing.

Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns.

Interferon and interferon-stimulated genes in HBV treatment.

Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs.

Role of epigenetic modification in interferon treatment of hepatitis B virus infection.

Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.

Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient's T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers.

Unlocking the Low-Temperature Potential of Propylene Carbonate to -30 °C via N-Methylpyrrolidone.

As the one of the core electrolyte solvents for Li-ion batteries, ethylene carbonate (EC) is still irreplaceable for its balance of ionic conductivity and interfacial stability. However, it also defines the boundary for the low-temperature performance of the battery because of its high melting point (36.4 °C). Its immediate sibling, propylene carbonate (PC), has been proposed as its convenient substitute for its much lower melting point (-48.8 °C). Unfortunately, the propylene carbonate-graphite anode interfacial problem has been a puzzle since the days before the advent of the Li-ion battery. Among various strategies to mitigate this issue, blending in selected strong solvents for Li+ to bring down propylene carbonate's presence in the solvation shell has been proven often effective but the mechanism from the interfacial chemistry perspective remains unexplored. Herein, we study a new cosolvent, N-methylpyrrolidone (NMP), for PC-based electrolyte and observe excellent reversibility that approaches the commercial standard, far beyond the similar systems in the past. To understand the mechanism, solvation chemistry analysis and in situ characterizations are undertaken to probe the interfacial chemistry from various standpoints. Based on these results and further theoretical calculation, it is proposed that N-methylpyrrolidone has mediated the reduction process of propylene carbonate to facilitate the growth of a solid electrolyte interphase (SEI) layer akin to ethylene carbonate. Finally, an electrolyte has also been successfully developed based on the NMP/PC couple to outperform the commercial electrolyte by a clear margin when tested in a LiNi0.8Co0.1Mn0.1O2-graphite cell at -30 °C.

Ginkgo biloba Extract Inhibited Cell Proliferation and Invasion by Stimulating TET2 Expression Through miR-29a in Colorectal Carcinoma Cells.

Ginkgo biloba extract (GBE) has antitumor and antioxidant properties, which play a role in regulating gene and protein expression. The ten-eleven translocation (TET) proteins have the ability to regulate epigenetic modifications. However, the abnormal expression of TET2 protein has also been demonstrated in cancer development. In the present study, we analyzed the effects of GBE administration on TET2 expression in human colorectal cancer (CRC). The Cancer Genome Atlas database suggested that the expression of TET2 was lost in CRC. To investigate the expression profiles of TET2, GBE was used to treat CRC cells. The results showed that GBE could increase the expression of TET2 and 5-hydroxymethylcytosine (5hmC). In addition, GBE inhibited cell growth and invasion in SW480 cells. Moreover, to confirm whether TET2 expression affected cell proliferation, apoptosis, migration, and invasion, TET2 was knocked down and a TET2-overexpressing vector was constructed in human CRC cells. The results showed that overexpression of TET2 induced cell proliferation and invasion. Bioinformatic analyses showed that TET2 is a target gene of microRNA-29a (miR-29a). Moreover, reduced expression of miR-29a and increased TET2 expression in CRC cells. GBE was also used to treat a tumor model in nude mice. Compared to the control group, tumor growth was inhibited, and there was increased expression of TET2 in the GBE-treatment group in vivo. In conclusion, these results indicated that GBE inhibited cell proliferation and invasion through TET2 protein expression regulated by miR-29a in the development of CRC.

Corrigendum: Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

[This corrects the article DOI: 10.3389/fimmu.2022.1025608.].

Phosphoproteomic analysis of ozone stress-responsive mechanisms in grapevine identifies KEG required for stress regulation.

The environmental damage caused by ozone is of increasing concern globally. The phosphoproteomics approach was used to explore the mechanisms underlying grapevine tolerance to ozone stress and identify phosphoproteins altered by ozone treatment. Results revealed that 194 of 2275 quantitatively analyzed phosphoproteins were significantly regulated after ozone treatment. Biological pathways related to transport were significantly enriched by the differentially regulated phosphoproteins. Among these phosphoproteins, the phosphorylation of RING E3 ligase in grape (V. vinifera KEEP ON GOING, VvKEG) decreased after ozone treatment. Over-expression of VvKEG in Arabidopsis decreased abscisic acid (ABA) sensitivity and enhanced ozone tolerance. Furthermore, VvKEG interacted with the ABA-responsive transcription factor ABSCISIC ACID-INSENSITIVE3 (ABI3). The exogenous application of ABA on grapevine leaves significantly influenced chlorophyll fluorescence, chlorophyll, and malondialdehyde (MDA) contents under ozone treatment; however, treatment with 150 µmol ABA aggravated ozone stress. These results indicate that phosphorylation modification provides information on ozone-induced processes and that VvKEG plays a critical role in these processes via regulation of the ABA signaling pathway in grape.

Dissociation of (Li2O2)0,+ on graphene and boron-doped graphene: insights from first-principles calculations.

Reducing charge overpotential is of great significance to enhance the efficiency and cyclability of Li-O2 batteries. Here, a dramatically reduced charge overpotential via boron-doped graphene as a catalytic substrate is successfully predicted. By first-principles calculations, from the perspective of reaction thermodynamics and kinetics, the results show that the electrochemical oxidation of the Li2O2+ cation is easier than the chemical oxidation of the neutral Li2O2 molecule, and the oxidation of (Li2O2)0,+ is facilitated by boron-doping in pristine graphene. More importantly, the results reveal the oxidation mechanism of (Li2O2)0,+: two-step dissociation with the LiO2 molecule as a reactive intermediate has advantages over one-step dissociation; the rate-determining step for the dissociation of (Li2O2+)G is the oxygen evolution process, while the lithium removal process is the rate-determining step for the dissociation of (Li2O20)G, (Li2O20)BG, and (Li2O2+)BG.

Robust Net Magnetic Moment in Janus V-Based Nitride MXenes: Insight from First-Principles Calculations.

Two-dimensional materials with robust magnetic moments are of great interest to explore the exciting physics and applications of nanoscale spintronic devices. However, the antiferromagnetic (AFM) ground states often restrict the applications of symmetric MXenes. Herein, we proposed a kind of Janus structure for the V-based nitride MXene V2N with one V layer replaced by the Ti/Cr layer. In this work, we demonstrated from the first-principles calculations that although the AFM ground states are formed, the Janus TiVN and CrVN monolayers possess net magnetic moments of 1.97 and 0.28 µB per formula unit, respectively. Moreover, the net magnetic moments of TiVN and CrVN monolayers are robust even if considerable strains (-8 to 8%) are applied. Our results also show that TiVN and CrVN exhibit half-metallic and metallic features, respectively. These properties widen the potential applications of Janus V-based MXenes in spintronic or other electronic devices.

Highly Enantioselective Construction of Dihydrooxazines via Pd-Catalyzed Asymmetric Carboetherification.

A straightforward synthesis of highly enantioenriched 5,6-dihydro-4H-1,2-oxazines is realized by Pd-catalyzed asymmetric carboetherification of γ,δ-alkenyl oximes with (hetero)aryl and alkenyl halides in the presence of a commercially available bisphosphine ligand. The enantioenriched products can be facilely converted to functionalized alcohols with high fidelity of chiral transfer.

p300 Acetylates JHDM1A to inhibit osteosarcoma carcinogenesis.

JHDM1A participates in cancer development via demethylate dimethyl histone H3 lysine 36 (H3K36me2). p300 is an intrinsic acetyltransferase. This study explored the acetyltransferase activity of p300 on JHDM1A and analyzed the JHDM1A acetylation on H3K36me2 demethylation in osteosarcoma. Co-immunoprecipitation (CoIP) and immunoblotting assay found that p300 directly acetylated JHDM1A at K409 residue in osteosarcoma MG-63 and HOS cells. Nucleosomes and mononucleosomes were prepared and found that acetylation of JHDMIA disrupted its association with nucleosomes and thereby impaired its capability to induce H3K36me2 demethylation. Moreover, chromatin immunoprecipitation (ChIP) assay discovered that the input levels of H3K36me2 in the promoter regions of p21 and puma were increased after acetylation of JHDM1A, which raised the p21 and puma mRNA levels in the cells. Finally, the analysis of JHDM1A acetylation on osteosarcoma cell proliferation and invasion, along with tumor growth pointed out that acetylation of JHDMIA inhibited the proliferation and invasion of osteosarcoma HOS cells, as well as suppressed the tumor growth of osteosarcoma. In conclusion, the outcomes of our research verified that p300 could directly acetylate JHDM1A at K409 site, which reduces the demethylation of H3K36me2, enhanced the transcription of p21 and puma, and thereby inhibited the growth and metastasis of osteosarcoma.

Teneligliptin inhibits lipopolysaccharide-induced cytotoxicity and inflammation in dental pulp cells.

Diabetes mellitus is one of the most common health threatening disorders. Patients with chronic diabetes are at high risk of contracting oral diseases, including dental pulp damage. In this study, we reviewed how Teneligliptin, a commonly used anti-diabetic agent, protected dental pulp cells from lipopolysaccharide (LPS)-induced cytotoxicity and improved their viability. The dental pulp cells treated with Teneligliptin were resistant to LPS-induced reactive oxygen species (ROS) and its byproduct 4-hydroxynonenal (4-HNE) generation. The Teneligliptin recovered LPS-induced a reduction of cellular glutathione and produced cytokine including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Mechanistically, we found that Teneligliptin suppressed LPS- that caused an expression of the cell surface receptor toll like receptor 4 (TLR-4) and the activation of JNK kinase and activator protein 1 (AP1) as well as the nuclear factor-κB (NF-κB) signal pathways. Collectively, our study demonstrates that the molecular mechanism Teneligliptin is a protective anti-diabetic agent in dental pulp cells and it has the potential to treat diabetes-associated dental pulp diseases.

Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis.

Long noncoding RNAs (lncRNAs) are involved in tumorigenesis. Previously, lncRNA MNX1-AS1 was reported to increase the malignancy of ovarian cancer, cervical cancer and lung cancer. However, the potential function of MNX1-AS1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that MNX1-AS1 was remarkably upregulated in HCC tissues and cell lines. Furthermore, MNX1-AS1 overexpression was related to advanced stage and metastasis, and predicted poor prognosis. Loss-of-function assays showed that MNX1-AS1 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Further investigation indicated that MNX1-AS1 silencing delayed HCC growth in vivo. Mechanistically, we identified that MNX1-AS1 was a competing endogenous RNA (ceRNA) for miR-218-5p. We demonstrated that MNX1-AS1 promoted COMMD8 expression through sponging miR-218-5p, and then contributed to HCC progression. Restoration of COMMD8 significantly reversed the effects of MNX1-AS1 knockdown. Taken together, our findings demonstrated that MNX1-AS1 promoted the malignant properties of HCC through targeting miR-218-5p/COMMD8 pathway.

RETRACTED: Alkannin inhibits proliferation, migration and invasion of hepatocellular carcinoma cells via regulation of miR-92a.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression.

Long noncoding RNAs (lncRNAs) have been acknowledged as vital regulators in tumorigenesis of human cancers, including hepatocellular carcinoma (HCC). LINC00461 has been found to promote progression of glioma and breast cancer. Nevertheless, the function of LINC00461 in HCC is still unknown. Here, we found that LINC00461 was upregulated in HCC tissues and positively correlated with advanced stage and metastasis. Furthermore, LINC00461 overexpression in HCC patients predicts unfavorable prognosis. Loss-of-function assays showed that LINC00461 silencing suppressed the proliferation, migration and invasion of HCC cells in vitro, and impeded tumor growth in vivo. Mechanistically, LINC00461 inversely regulates miR-149-5p abundance in HCC. Further investigation indicated that LINC00461 was a competing endogenous RNA (ceRNA) by directly sponging miR-149-5p in HCC cells. Moreover, LRIG2 was identified as the downstream target of miR-149-5p and its expression was regulated by LINC00461/miR-149-5p axis. Restoration of LRIG2 reversed LINC00461 knockdown attenuated HCC cell proliferation, migration and invasion. In summary, our findings revealed that LINC00461 is an oncogene in HCC through regulating miR-149-5p/LRIG2 pathway.

The crab Relish plays an important role in white spot syndrome virus and Vibrio alginolyticus infection.

Relish is a transcription factor and forms an important part of the immune deficiency signaling pathway. In the current study, a Relish homolog was cloned from the hemolymph of Scylla paramamosain using RT-PCR and RACE. The full length cDNA of Relish consists of 4263 base pairs (bp), including a 3552 bp open reading frame encoding a 1184 amino acid protein. The data showed that Relish was highly expressed in the gonad and digestive organs of S. paramamosain. Furthermore, the expression of Relish was up-regulated by infection with white spot syndrome virus (WSSV) or Vibrio alginolyticus. When Relish was knocked down, immune genes such as Janus Kinase, signal transducer and activator of transcription, crustin antimicrobial peptide, prophenoloxidase, C-type-lectin and myosin-II-essential-light-chain-like-protein were significantly down-regulated (P < 0.01), and Toll-like receptor was significantly up-regulated (P < 0.01) in hemocytes. The mortality of WSSV-infected or V. alginolyticus-infected crabs was enhanced following Relish knockdown. Thus, Relish is very important in the progression of WSSV and V. alginolyticus infection. It was found that Relish knockdown caused the highest level of apoptosis in the disease-free group, and higher levels of apoptosis in the WSSV group and V. alginolyticus group compared with that in the control group. Knockdown of Relish influenced the activity of phenoloxidase (PO) and superoxide dismutase (SOD), and total hemocyte count (THC) following WSSV or V. alginolyticus infection, indicating that Relish plays a regulatory role in the immune response to WSSV or V. alginolyticus infection in crabs. Thus, we conclude that Relish may anticipate host defense mechanisms against pathogen infection by affecting apoptosis, THC, PO activity and SOD activity.