BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

Deletion of DP148R, DP71L, and DP96R Attenuates African Swine Fever Virus, and the Mutant Strain Confers Complete Protection against Homologous Challenges in Pigs.

The African swine fever virus (ASFV) has caused a devastating pandemic in domestic and wild swine, causing economic losses to the global swine industry. Recombinant live attenuated vaccines are an attractive option for ASFV treatment. However, safe and effective vaccines against ASFV are still scarce, and more high-quality experimental vaccine strains need to be developed. In this study, we revealed that deletion of the ASFV genes DP148R, DP71L, and DP96R from the highly virulent isolate ASFV CN/GS/2018 (ASFV-GS) substantially attenuated virulence in swine. Pigs infected with 104 50% hemadsorbing doses of the virus with these gene deletions remained healthy during the 19-day observation period. No ASFV infection was detected in contact pigs under the experimental conditions. Importantly, the inoculated pigs were protected against homologous challenges. Additionally, RNA sequence analysis showed that deletion of these viral genes induced significant upregulation of the host histone H3.1 gene (H3.1) and downregulation of the ASFV MGF110-7L gene. Knocking down the expression of H3.1 resulted in high levels of ASFV replication in primary porcine macrophages in vitro. These findings indicate that the deletion mutant virus ASFV-GS-Δ18R/NL/UK is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce full protection against the highly virulent ASFV-GS virus strain. IMPORTANCE Ongoing outbreaks of African swine fever (ASF) have considerably damaged the pig industry in affected countries. Thus, a safe and effective vaccine is important to control African swine fever spread. Here, an ASFV strain with three gene deletions was developed by knocking out the viral genes DP148R (MGF360-18R), NL (DP71L), and UK (DP96R). The results showed that the recombinant virus was completely attenuated in pigs and provided strong protection against parental virus challenge. Additionally, no viral genomes were detected in the sera of pigs housed with animals infected with the deletion mutant. Furthermore, transcriptome sequencing (RNA-seq) analysis revealed significant upregulation of histone H3.1 in virus-infected macrophage cultures and downregulation of the ASFV MGF110-7L gene after viral DP148R, UK, and NL deletion. Our study provides a valuable live attenuated vaccine candidate and potential gene targets for developing strategies for anti-ASFV treatment.

Low cycle number multiplex PCR: A novel strategy for the construction of amplicon libraries for next-generation sequencing.

Multiplex PCR is a critical step when preparing amplicon library for next-generation sequencing. However, there are several challenges related to multiplex PCR including poor uniformity, nonspecific amplification, and primer-dimers. To address these issues, we propose a novel solution strategy that involves using a low cycle number (<10 cycles) in multiplex PCR and then employing carrier DNAs and magnetic beads for the selection of targeted products. This technique improves the amplicon uniformity while also reducing primer-dimers and PCR artifacts. To evaluate our technique, we initially utilized 120 DNA fragments from mouse genome containing single nucleotide polymorphism (SNP) sites. Sequencing results demonstrated that with only 7 cycles of multiplex PCR, 95.8% of the targeted SNP sites were mapped, with a coverage of at least 1×. The average sequencing depth of all amplicons was 1705.79 ± 1205.30×; 87% of them reached a coverage depth that exceeded 0.2-fold of the average sequencing depth. Our method had a greater uniformity (87%) when compared to Hi-Plex PCR (53.3%). Furthermore, we validated our strategy by randomly selecting 90 primer pairs twice from the initial set of 120 primer-pairs. Next, we used the same protocol to prepare amplicon libraries. The two groups had an average sequencing depth of 1013.30 ± 585.57× and 219.10 ± 158.27×, respectively; over 84% of the amplicons had a sequencing depth that exceeded 0.2-fold of average depth. These results suggest that the use of a low cycle number in multiplex PCR is a cost-effective and efficient approach for the preparation of amplicon libraries.

Long-life triclosan exposure induces ADHD-like behavior in rats via prefrontal cortex dopaminergic deficiency.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

The Optimization Design of Macrophage Membrane Camouflaging Liposomes for Alleviating Ischemic Stroke Injury through Intranasal Delivery.

Ischemic stroke is associated with a high mortality rate, and effective treatment strategies are currently lacking. In this study, we aimed to develop a novel nano delivery system to treat ischemic stroke via intranasal administration. A three-factor Box-Behnken experimental design was used to optimize the formulation of liposomes co-loaded with Panax notoginseng saponins (PNSs) and Ginsenoside Rg3 (Rg3) (Lip-Rg3/PNS). Macrophage membranes were coated onto the surface of the optimized liposomes to target the ischemic site of the brain. The double-loaded liposomes disguised by macrophage membranes (MM-Lip-Rg3/PNS) were spherical, in a "shell-core" structure, with encapsulation rates of 81.41% (PNS) and 93.81% (Rg3), and showed good stability. In vitro, MM-Lip-Rg3/PNS was taken up by brain endothelial cells via the clathrin-dependent endocytosis and micropinocytosis pathways. Network pharmacology experiments predicted that MM-Lip-Rg3/PNS could regulate multiple signaling pathways and treat ischemic stroke by reducing apoptosis and inflammatory responses. After 14 days of treatment with MM-Lip-Rg3/PNS, the survival rate, weight, and neurological score of middle cerebral artery occlusion (MCAO) rats significantly improved. The hematoxylin and eosin (H&E) and TUNEL staining results showed that MM-Lip-Rg3/PNS can reduce neuronal apoptosis and inflammatory cell infiltration and protect the ischemic brain. In vivo biological experiments have shown that free Rg3, PNS, and MM-Lip-Rg3/PNS can alleviate inflammation and apoptosis, especially MM-Lip-Rg3/PNS, indicating that biomimetic liposomes can improve the therapeutic effects of drugs. Overall, MM-Lip-Rg3/PNS is a potential biomimetic nano targeted formulation for ischemic stroke therapy.

YAP nuclear translocation facilitates radiation resistance in nasopharyngeal carcinoma cells.

OBJECTIVES: Investigate the role of the Hippo-YAP signaling pathway in radioresistant Nasopharyngeal Carcinoma (NPC). METHODS: Establishment of radioresistant CNE-1 cells (CNE-1-RR) by gradually increasing ionizing radiation (IR) doses, and identifying the apoptosis of CNE-1-RR by flow cytometry. We employed immunoblot and immunofluorescence staining to detect the expression of YAP in both CNE-1-RR and control group cells. Moreover, we validated the role of YAP in CNE-1-RR by inhibiting its nuclear translocation. RESULTS: In contrast to the control group, radioresistant NPC cells demonstrated significant YAP dephosphorylation and nuclear translocation. CNE-1-RR cells exhibited enhanced activation of γ-H2AX (Ser139) upon exposure to IR and greater recruitment of double-strand breaks (DSBs) repair-related proteins. Additionally, inhibiting YAP nuclear translocation in radioresistant CNE-1-RR cells significantly increased their sensitivity to radiotherapy. CONCLUSIONS: The present investigation has unveiled the intricate mechanisms and physiological roles of YAP in CNE-1-RR cells exhibiting resistance to IR. Based on our findings, it can be inferred that a combinational therapeutic strategy involving radiotherapy and inhibitors that impede the nuclear translocation of YAP holds promising potential for treating radioresistant NPC.

MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer.

OBJECTIVE: The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer. METHODS: MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin. RESULTS: The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR­590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR­590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p. CONCLUSION: The present study demonstrates that miR­590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR­590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR­590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer.

Overexpression of RtSYP121 confers cadmium colerance by promoting vesicle trafficking, maintaining ion homeostasis, and alleviating photosynthetic inhibition in Arabidopsis.

Cadmium (Cd) is a toxic heavy metal in soil that seriously threatens crop production, food security, and human health. Syntaxins, a prototype family of Soluble N-ethyl-maleimide-associated protein receptors (SNAREs) involved in vesicle trafficking, are implicated in resistance to abiotic stresses, including Cd stress, but the molecular mechanisms underlying the involvement of syntaxins in Cd tolerance in plants are unclear. In this study, we isolated and functionally characterized the syntaxin gene RtSYP121 from Reaumuria trigyna to evaluate its potential for phytoremediation. RtSYP121 resides in the plasma membrane. The transcriptional level of RtSYP121 was strongly increased by salt, drought, and Cd stress. Overexpression of RtSYP121 significantly enhanced the Cd tolerance of transgenic Arabidopsis. The Cd tolerance of transgenic plants mainly depended on elevated vesicle trafficking, which increased the content of K+ and Ca2+ and thus decreased the accumulation of Cd2+ by regulating the delivery or activity of ion transporters, channels, and pumps. Moreover, overexpression of RtSYP121 in Arabidopsis ameliorated Cd stress-induced phytotoxic effects, including growth inhibition, ROS burst, photosynthetic impairment, and cell death. Therefore, we suggest that RtSYP121 plays multiple roles in the plant response to Cd stress by promoting vesicle trafficking, maintaining ion homeostasis, and alleviating photosynthetic inhibition.

Clinical characteristic and pathogenesis of tumor-induced acute pancreatitis: a predictive model.

BACKGROUND: The aim of our study was to investigate the clinical characteristics and pathogenesis of tumor-induced acute pancreatitis (AP), and to develop a reliable prediction model of the clinical features to guide the diagnosis and treatment. METHODS: Patients with AP between January 2013 and December 2021 were enrolled in the study and were subdivided into the tumor group and the non-tumor group. The tumor group was subdivided into three groups based on the primary sites. Characteristic parameters, laboratory and imaging results were compared between groups. Least absolute shrinkage and selection operator regression model, XGBoost and random forest model were used to select the predictors associated with tumor-induced AP. Logistic regression analysis was used to validate the performance of the selected predictors and a nomogram was established to provide individualized probability of a tumor origin for AP. RESULTS: A total amount of 8970 patients were admitted for AP during the study period, and 8637 AP patients were enrolled in the study. Of these, 100 cases (1.16%) were tumor-induced AP. The tumor group was significantly older than the non-tumor group (t = 6.050, p = 0.000). Mild AP was observed in 90 cases, moderate AP in 9 cases and severe AP in one case. Tumors respectively originated from distal bile duct (14 cases), ampulla (13 cases) and pancreas (73 cases). The median time from initial AP to tumor diagnosis was 8.57 weeks and the median number of episode was 2 in the tumor group, which significantly surpassed the non-tumor group (p = 0.000). Age, white blood cell count, percentage of neutrophils, pancreatic or bile duct dilation and recurrent attacks were selected independent predictors for tumor origin. A nomogram model based on these factors was established. CONCLUSION: For patients with agnogenic AP, elderly man, recurrent attacks, pancreatic or bile duct dilatation and continuous no significant increase of inflammatory markers prompt to further screening of pancreatic biliary and ampulla.

A systematic analysis of molecular mechanisms in non-metastatic renal cancer delineates affected regulatory pathways and genes in tumor growth.

In the recent century, Kidney cancer has emerged as one of the critical renal diseases. Therefore, we analyzed gene expression profiles of non-metastatic kidney cancer to find mechanisms associated with the early-stage pathogenesis of the disease. We concentrated on the most dysregulated genes in expression to discover possible unknown proliferative molecular mechanisms and oncogenic pathways promoting kidney renal cancer growth. Survival analysis, expression profiling, and gene set over-representation analysis were conducted on the most upregulated and most down-regulated genes alongside the hub genes. Our results demonstrated that pathways engaged in the metabolism of amino acids and carbohydrates and those involved in peroxisome organization were shown to be important in developing benign tumors. Furthermore, upregulation of genes such as CXCL9 and 10 genes and CXCR4 in chemokine response pathways would bolster differentiation and engagement of immune cells in the tumor microenvironment. C3, one of the essential members of the complement system, with a high degree and betweenness centrality in the PPI network, upregulated significantly not only in our analysis but also in the validation expression profiling results and survival analysis. We also identified genes such as TYROBP, ITGB2, and EGFR to be engaged in both immunological pathways and superoxide pathways. Furthermore, we found that downregulation of Aldolase B engaged in Glycolysis and Gluconeogenesis pathways would help develop benign tumors. Finally, many top hub genes, including TYMS, PTPRC, AURKA, FN1, UBE2C, and CD53 were proposed to be engaged in the progression of non-metastatic renal tumors. This holistic interrogation calls attention to investigate further and experimentally validate the proposed molecular mechanisms.

Trees and shrubs from a post-industrial area high in calcium and trace elements: the potential of dendroremediation.

NOVELTY STATEMENT: That is probably the first study to date of trees and shrubs differing in age and growing on post-industrial soil contaminated with calcium (Ca) and selected toxic metals/metalloids. The obtained results show that an alkaline reaction (less than 9) of soil and an unusually high Ca concentration may help the studied tree species to adapt/survive in unfavorable habitat conditions (high concentration of toxic elements). The efficiency of phytoextraction of toxic elements was so high that, especially for forest animals (roe-deer) that consume, e.g., willow shoots, it could pose a serious threat to health and life, both for them and potentially for humans.

The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses.

Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL.

Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

Accurate prediction of protein-ATP binding residues using position-specific frequency matrix.

Knowledge of protein-ATP interaction can help for protein functional annotation and drug discovery. Accurately identifying protein-ATP binding residues is an important but challenging task to gain the knowledge of protein-ATP interactions, especially for the case where only protein sequence information is given. In this study, we propose a novel method, named DeepATPseq, to predict protein-ATP binding residues without using any information about protein three-dimension structure or sequence-derived structural information. In DeepATPseq, the HHBlits-generated position-specific frequency matrix (PSFM) profile is first employed to extract the feature information of each residue. Then, for each residue, the PSFM-based feature is fed into two prediction models, which are generated by the algorithms of deep convolutional neural network (DCNN) and support vector machine (SVM) separately. The final ATP-binding probability of the corresponding residue is calculated by the weighted sum of the outputted values of DCNN-based and SVM-based models. Experimental results on the independent validation data set demonstrate that DeepATPseq could achieve an accuracy of 77.71%, covering 57.42% of all ATP-binding residues, while achieving a Matthew's correlation coefficient value (0.655) that is significantly higher than that of existing sequence-based methods and comparable to that of the state-of-the-art structure-based predictors. Detailed data analysis show that the major advantage of DeepATPseq lies at the combination utilization of DCNN and SVM that helps dig out more discriminative information from the PSFM profiles. The online server and standalone package of DeepATPseq are freely available at: https://jun-csbio.github.io/DeepATPseq/for academic use.

Rationally designed NiMn LDH@NiCo2O4core-shell structures for high energy density supercapacitor and enzyme-free glucose sensor.

Exploring high-efficiency and low-cost bifunctional electrodes for supercapacitors and sensors is significant but challenging. Most of the existing electrodes are mostly single-functional materials with simple structure. Herein, NiCo2O4nanowires as the core and NiMn layered double hydroxide (LDH) as the shell is directly grownin situon carbon cloth (CC) to form a heterostructure (NiMn LDH@NiCo2O4/CC). The performance in supercapacitors and enzyme-free glucose sensing has been systematically studied. Compared with a single NiCo2O4nanowire or NiMn LDH nanosheet, the heterogeneous interface produced by the unique core-shell structure has stronger electronic interaction and abundant active surface area, which shows excellent electrochemical performance. Electrochemical tests demonstrate that the NiMn LDH@NiCo2O4/CC core-shell electrode possesses an area specific capacitance of 2.40 F cm-2and a rate capability of 76.22% at 20 mA cm-2. Simultaneously, asymmetric supercapacitor is assembled with it as the positive electrode and NiFe LDH@NiCo2O4/CC as the negative electrode. The supercapacitor possesses an energy density of 47.74 Wh kg-1when the power density is 175 W kg-1, revealing excellent performance and maintains cycle stability of 93.48% after 6000 cycles at 10 mA cm-2. Additionally, the electrode applied as enzyme-free glucose sensor electrode also displays outstanding sensitivity of 2139µA mM-1cm-2, wide detection range (2µM-3mM and 4-8 mM) and low detection limit of 210 nM, representing good anti-interference performance. This work reveals the multi-metal synergy and rationally designed core-shell structure is critical to the electrochemical performance of bifunctional electrodes.

circBICD2 targets miR-149-5p/IGF2BP1 axis to regulate oral squamous cell carcinoma progression.

BACKGROUND: Circular RNAs (circRNAs) are related to oral squamous cell carcinoma (OSCC) progression. circRNA bicaudal D cargo adaptor 2 (circBICD2) has been reported to be abnormally expressed in OSCC. However, the function and mechanism of this circRNA in OSCC progression remain largely unknown. METHODS: circBICD2, microRNA-149-5p (miR-149-5p), and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) abundances were examined via quantitative reverse transcription polymerase chain reaction or Western blot. The function of circBICD2 was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, wound healing, transwell, specific kits, Western blot, and xenograft analyses. Dual-luciferase reporter analysis and RNA immunoprecipitation were carried out to analyze the binding interaction. RESULTS: circBICD2 expression was enhanced in OSCC tissues and cells. circBICD2 silence suppressed OSCC cell proliferation, migration, invasion, and glutaminolysis and facilitated apoptosis. miR-149-5p was targeted via circBICD2 and decreased in OSCC tissues and cells. miR-149-5p knockdown attenuated silence of circBICD2 on the influence of OSCC cell proliferation, apoptosis, migration, invasion, and glutaminolysis. IGF2BP1 was targeted via miR-149-5p, and circBICD2 could regulate IGF2BP1 via miR-149-5p. IGF2BP1 interference constrained OSCC cell proliferation, migration, invasion, and glutaminolysis and promoted apoptosis. circBICD2 silence reduced OSCC cell growth in xenograft model. CONCLUSION: circBICD2 knockdown repressed OSCC cell proliferation, migration, invasion, and glutaminolysis and increased apoptosis via modulating miR-149-5p/IGF2BP1 axis, which might act as a potential target for OSCC treatment.

Molecular characterization and immune functional analysis of IRF2 in common carp (Cyprinus carpio L.): different regulatory role in the IFN and NF-κB signalling pathway.

BACKGROUND: Interferon regulatory factor 2 (IRF2) is an important transcription factor, which can regulate the IFN response and plays a role in antiviral innate immunity in teleost. RESULTS: In the present study, the full-length cDNA sequence of IRF2 (CcIRF2) was characterized in common carp (Cyprinus carpio L.), which encoded a protein containing a conserved DNA-binding domain (DBD) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF2 was most closely related with IRF2 of Ctenopharyngodon idella. CcIRF2 transcripts were detectable in all examined tissues, with higher expression in the gills, spleen and brain. CcIRF2 expression was upregulated in immune-related tissues of common carp upon polyinosinic:polycytidylic acid (poly (I:C)) and Aeromonas hydrophila stimulation and induced by poly (I:C), lipopolysaccharide (LPS), peptidoglycan (PGN) and flagellin in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs). In addition, overexpression of CcIRF2 decreased the expression of IFN and IFN-stimulated genes (ISGs), and a dual-luciferase reporter assay revealed that CcIRF2 could increase the activation of NF-κB. CONCLUSIONS: These results indicate that CcIRF2 participates in antiviral and antibacterial immune response and negatively regulates the IFN response, which provide a new insight into the regulation of IFN system in common carp, and are helpful for the prevention and control of infectious diseases in carp farming.

Long non-coding RNA H19 acts as a microRNA-194 sponge to inhibit the apoptosis and promote the proliferation of hypertrophic scar fibroblasts.

The effects of long non-coding RNAs (lncRNAs) on the proliferation of hypertrophic scars have been described, however, the underlying mechanisms are not well characterized. The present study aimed to investigate the mechanisms of lncRNA H19 in hypertrophic scars. The effects of the lncRNA H19 on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSFs) were analyzed using 5'-ethynyl-2'-deoxyuridine staining, flow cytometry, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The results revealed H19 promoted the proliferation and inhibited the apoptosis in HSF. In addition, the binding associations between H19 and microRNA-194 (miR-194), and miR-194 and insulin-like growth factor I receptor (IGF1R) were identified using bioinformatics screening and verified using dual-luciferase assays. Furthermore, the effects of the IGF1R knockdown on H19-induced HSF phenotypes and regulation over the p38 MAPK pathway were determined. Mechanistically, miR-194 was identified as the downstream effector of the H19-mediated phenotypes of HSFs through its ability to directly target IGF1R, thus modulating the p38 MAPK signaling pathway. In conclusion, the findings suggested that H19 may inhibit the apoptosis and promote the proliferation of HSFs through the miR-194/IGF1R/p38 MAPK signaling axis, thereby contributing to the progression of hypertrophic scars. These findings may provide novel targets for the treatment of hypertrophic scars.

A leucoanthocyanidin dioxygenase gene (RtLDOX2) from the feral forage plant Reaumuria trigyna promotes the accumulation of flavonoids and improves tolerance to abiotic stresses.

Reaumuria trigyna, a Tamaricaceae archaic recretohalophyte, is an important feral forage plant in the desert steppe of northwestern China. We identified two significantly differentially expressed leucoanthocyanidin dioxygenase genes (RtLDOX/RtLDOX2) and investigated the function and characteristics of RtLDOX2. RtLDOX2 from R. trigyna was rapidly upregulated by salt, drought, and abscisic acid, consistent with the stress-related cis-regulatory elements in the promoter region. Recombinant RtLDOX2 converted dihydrokaempferol to kaempferol in vitro, and was thus interchangeable with flavonol synthase, a dioxygenase in the flavonoid pathway. Transgenic plants overexpressing RtLDOX2 accumulated more anthocyanin and flavonols under abiotic stresses, speculating that RtLDOX2 may act as a multifunctional dioxygenase in the synthesis of anthocyanins and flavonols. Overexpression of RtLDOX2 enhanced the primary root length, biomass accumulation, and chlorophyll content of salt-, drought-, and ultraviolet-B-stressed transgenic Arabidopsis. Antioxidant enzyme activity; proline content; and expression of antioxidant enzyme, proline biosynthesis, and ion-transporter genes were increased in transgenic plants. Therefore, RtLDOX2 confers tolerance to abiotic stress on transgenic Arabidopsis by promoting the accumulation of anthocyanins and flavonols. This in turn increases reactive oxygen species scavenging and activates other stress responses, such as osmotic adjustment and ion transport, and so improves tolerance to abiotic stresses.

Silica-polydopamine hybrids as light-induced oxidase mimics for colorimetric detection of pyrophosphate.

In this study, silica-polydopamine hybrids (SPDA) were fabricated by a facile and one-step heating method using dopamine and (3-aminopropyl)triethoxysilane (APTES) as the reaction reagents. It was firstly found that light illuminated-SPDA could oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue ox-TMB. The coloration process was quenched very efficiently via the addition of Cu2+. The presence of pyrophosphate ion (PPi) in the solution of light-illuminated SPDA-Cu2+-TMB induced the recovery of the coloration process. The recovery occurred because PPi coordinated with Cu2+, effectively sequestering the ion from SPDA. A calibration curve was developed that is related to the extent of absorption recovery to [PPi], making the SPDA-Cu2+-TMB system a sensitive and selective turn-on sensor for PPi detection. The limit-of-detection (LOD) for PPi was 0.06 µmol L-1 (S/N = 3) with a linear dynamic range of 0.1-30 µmol L-1 and the calibration curve of linear equation is given as: y = 0.00146x + 0.05096 (r = 0.9974). The proposed method has been successfully applied to the detection of PPi in human serum with satisfactory recovery. The simplicity, low cost, high sensitivity, good reproducibility and excellent selectivity of the PPi detection platform based on the light-induced oxidase mimicking property of SPDA makes it promising for further applications of SPDA in chemo/biosensing.