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A better understanding of the factors that reduce bundle-sheath cell leakage to CO2 (Փ), enhance 13C carbon isotope discrimination, and enhance the photosynthetic capacity of barley leaves will be useful to develop a nutrient- and water-saving strategy for dry-land farming systems. Therefore, barley plants were exposed to a novel nitrification inhibitor (NI) (3,4-dimethyl-1H-pyrazol-1-yl succinic acid) (DMPSA) and a urease inhibitor (UI) (N-butyl thiophosphorictriamide (NBPT)) with mulched drip fertigation treatments, which included HF (high-drip fertigation (370 mm) under a ridge furrow system), MF (75% of HF, moderate-drip fertigation under a ridge furrow system), LF (50% of HF, low-drip fertigation under a ridge furrow system), and TP (traditional planting with no inhibitors or drip fertigation strategies). The results indicated that the nitrification inhibitor combined with mulched drip fertigation significantly reduced bundle-sheath cell leakage to CO2 (Փ) as a result of increased soil water content; this was demonstrated by the light and CO2 response curves of the photosynthesis capacity (An), the apparent quantum efficiency (α), and the 13C-photosynthate distribution. In the inhibitor-based strategy, the use of the urease and nitrification inhibitors reduced Փ by 35% and 39% compared with TP. In the NI-HF strategy, it was found that barley could retain the maximum photosynthesis capacity by increasing the leaf area index (LAI), An, rubisco content, soluble protein, dry matter per plant, and productivity. The CO2 and light response curves were considerably improved in the NI-HF and NI-MF treatments due to a higher 13C carbon isotope (Δ‰), respiration rate (Rd), and Ci/Ca, therefore obtaining the minimum Փ value. With both inhibitors, there was a significant difference between HF and LF drip fertigation. The NI-MF treatment significantly increased the grain yield, total chlorophyll content, WUE, and NUE by 52%, 47%, 57%, and 45%, respectively. Collectively, the results suggest that the new nitrification inhibitor (DMPSA) with HF or MF mulched drip fertigation could be promoted in semi-arid regions in order to mitigate bundle-sheath cell leakage to CO2 (Փ), without negatively affecting barley production and leading to the nutrient and water use efficiency of barley. [ABSTRACT FROM AUTHOR]

Lincomycin (LC) is an extensively applied broad-spectrum antibiotic, and its considerable residues in wastewater have caused a series of environmental problems, which makes degradation of LC wastewater extremely urgent. In this work, we have constructed a novel boron nitride (BN) and samarium (Sm) co-modified Ti/PbO2 as anode for high-performance degradation of LC wastewater. Compared with Ti/PbO2, Ti/PbO2-Sm, and Ti/PbO2-BN electrodes, Ti/PbO2-BN-Sm electrode with smaller pyramidal particles possesses higher oxygen evolution potential (2.32 V), excellent accelerated service life (103 h), and outstanding electrocatalytic activity. The single-factor experiments demonstrate that under optimized conditions (current density of 20 mA.cm-2, 6.0 g L-1 Na2SO4, pH 9, and temperature of 30°C), removal rate and COD degradation rate of LC at 3 h have reached 92.85% and 89.11%, respectively. At the same time, degradation of LC is in accordance with the primary kinetic model. Based on the analysis of high-performance liquid chromatography-mass spectrometry (HPLC-MS), four possible degradation pathways are hypothesized. Therefore, efficient electrochemical degradation of LC by using an extremely long-life Ti/PbO2 electrode with high catalytic activity may be a promising method. [ABSTRACT FROM AUTHOR]

A novel isoxazoline‐based porous adsorbent (PB‐TTNO) is prepared by click polymerization and freeze‐drying from a methyl‐containing bis(nitrile oxide) stable at room temperature. The introduction of four methyl groups around the nitrile oxide group reduces the activity of the bis(nitrile oxide) and make it react more mildly with polybutadiene, resulting in PB‐TTNO with a more uniform pore size. Meanwhile, the electron‐donating methyl groups further increase the π–π interaction between the polymer benzene ring and the TNT benzene ring. The π–π interaction enables one benzene ring in the polymer to interact with two TNT molecules to form a sandwich structure, which further improves the adsorption capacity. The synergistic effect of dual π–π interactions and dipole‐π interactions makes the maximum adsorption capacity of PB‐TTNO reach 235.3 mg g−1 within 12 h at 25°C. The factors such as pH value, adsorbent dosage, contact time, initial TNT concentration, and temperature are also discussed. The adsorption kinetics fit well with the pseudo‐second‐order model, and the Langmuir model exhibits better correlation for equilibrium data analysis. In addition, the adsorption data of PB‐TTNO in real water samples are similar to those in laboratory, and the maximum adsorption capacity decreases by only 15% after five adsorption–desorption cycles. [ABSTRACT FROM AUTHOR]

MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics. • A multitude of clinical data revealed the important role of miR-21 in breast cancer. • RNA nanoparticles carrying anit-miR-21 were successfully constructed in the study. • The efficient cellular binding and uptake of 3WJ-EGFRapt/anti-miR-21 NPs were tested. • 3WJ-EGFRapt/anti-miR-21 NPs suppressed cancer cell invasion, migration, and colony formation. • The remarkable synergistic effect of miR-21 knockdown with chemotherapy was revealed. [ABSTRACT FROM AUTHOR]

• Biodegradable poly(amino acid) capsules based on PGA and POR. • Stiffness and surface charges affected the cellular uptake efficiency. • The degradability and uptake efficiency dominate the cytotoxicity of carriers@Dox. Constructing intracellular degradable drug delivery vehicles is critical to fully exert the function of loaded drugs. Considering the poly (amino acid) is sensitively degradable to acid and enzyme which indwell in the mature lysosome, we here presented the poly(amino acid) capsules constructed by the synthetic poly(amino acid), (poly-glutamic acid, PGA and poly-ornithine, POR). The fabrication of Dox loaded poly (amino acid) capsules was demonstrated, and was thoroughly characterized by various techniques, including Zetasizer, SEM, TEM, fluorescent microscopy, and confocal laser scan microscopy. By controlling fabrication process, we tuned the carriers with different physical properties (charges and stiffness). Then, we thoroughly investigated the effects of these properties on the intracellular uptake and anti-cancer abilities of various carriers@Dox. In addition, the degradability of poly(amino acid) capsules was studied to reveal the release profiles of the carriers with or without templates from the side aspect. We found the positively charged and stiffer carriers mainly contributed to the cellular uptake process and amount, while both the uptake amount and degradability of the endocytosed carriers@Dox played a critical role on the cytotoxicity. We believe the findings here could pave the way for designing poly(amino acid) capsules or other degradable polymers based on poly(amino acid) as the drug delivery vehicles. [ABSTRACT FROM AUTHOR]

It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions for disease treatment, tissue engineering, bioimaging, etc. Inspired by the coordinative interactions between histidine and metal ions, we present the facile synthesis of hexahistidine (His 6)-metal assembly (HmA) particles under mild conditions for the first time. The HmA particles presented a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. In addition, HmA encapsulation largely improved the antitumor ability of camptothecin (CPT) relative to free CPT. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields. It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions. Inspired by the coordinative interactions between histidine and metal ions, we present for the first time the facile synthesis of Hexahistidine (His 6)-metal assembly (HmA) particles under mild conditions. The HmA particles exhibited a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields. [ABSTRACT FROM AUTHOR]

Cancer is the second most common cause of death, and nanomedicine is regarded as one of the strategies that may revolutionize cancer treatments. However, the tumor microenvironment (e.g., increased interstitial fluid pressure and dense extracellular matrix) hinders the penetration of nanomedicine into tumor cells, which leads to a short acting time and low drug concentration with tumors, eventually leading to a high recurrence rate and therapeutic failure in clinics. Developing a delivery system with deep penetration ability into the tumor has always been pursued and highly desirable for cancer treatments. Inspired by the high cellular uptake efficiency of enveloped viruses with rough and nanoscale surfaces, we constructed polystyrene nanoparticles (NPs) with similar sizes and charges, but with different surface topologies at the molecular level, by conjugating poly(propylene imine) (PPI) dendrimers with different generations onto the NPs. We found that subtle changes made to the surficial chemical properties led to changes in surface roughness and wettability, which considerably influenced the cellular internalization, endocytosis mechanism, and penetration into the tumor model both in vitro and in vivo. This will shed light on the future design of drug delivery vehicles and facilitate understanding the interactions between NP surfaces and cells, as well as tumor penetration. [ABSTRACT FROM AUTHOR]

This cover image by Yewei Xu and Hongyang Deng demonstrates the adsorption mechanism of TNT by the isoxazoline-based porous polymer. The polymer has an unprecedented adsorption capacity for TNT through the - and dipole- interactions. In addition, the polymer possesses recycling properties. [Extracted from the article]

Post-translational modifications of viral proteins play important roles in regulating viral replication. Here we demonstrated that the PB2 of influenza A virus (IAV) can be modified by NEDD8. We revealed that E3 ligase HDM2 can promote PB2 NEDDylation. Overexpression of either NEDD8 or HDM2 can inhibit IAV replication, while knockdown of HDM2 has the opposite effect. Then we identified residue K699 in PB2 as the major NEDDylation site. We found that NEDDylation deficient PB2 mutant (PB2 K699R) has a longer half-life than wild-type PB2, indicating that NEDDylation of PB2 reduces its stability. We generated an IAV mutant in which PB2 was mutated to PB2 K699R (WSN-PB2 K699R) and examined the replication of WSN and WSN-PB2 K699R viruses in both MDCK and A549 cells and found that the replication of WSN-PB2 K699R was more efficient than wild-type WSN. In addition, we observed that overexpression of NEDD8 significantly inhibited the replication of WSN, but not WSN-PB2 K699R. The infection assay in mice showed that WSN-PB2 K699R exhibited enhanced virulence in mice compared to WSN, suggesting that NEDDylation of PB2 reduced IAV replication in vivo. In conclusion, we demonstrated that NEDDylation of PB2 by HDM2 negatively regulates IAV infection. [ABSTRACT FROM AUTHOR]

• The TA/gelatin multilayer coating was built and well characterized. • The antioxidant properties of TA/gelatin avoid cells from damage under ROS. • Cells seeded onto TA/gelatin displayed fast attachment and spreading, and quick proliferation. • TA/gelatin enhanced osteogenesis of bone cells in vitro and bone formation in vivo. Bone related implants have huge potential market in global. Improving the implant outcomes and probability of implant success are highly pursued to relieve the pain of patients and burden on native healthy system. There are growing evidence to support reactive oxygen species (ROS) directly involved in bone diseases and failure of implants. Taking advantage of the antioxidant property of tannic acid (TA) and biocompatibility of gelatin (Gel), the TA/Gel multilayer film was fabricated by layer by layer method, and the growing process of this film was monitored by QCM-D. The physical properties of TA/Gel film were further well characterized and modulated. In cellular test, TA/Gel multilayer film displayed good antioxidant properties under ROS stress environment (after H 2 O 2 treatment flourscence intensity increased 38.9-fold for glasses, only ˜6-fold for (TA/Gel) 8), facilitating cell attachment, fastening spreading at early stage and accelerating proliferation in beginning 2 day. Area per cell on (TA/ Gel) 4–0.15 M is 1.5-fold higher than that on glass at 2 h, while it became 2.3-fold higher at 4 h. Moreover, these films performed both enhanced osteogenesis in vitro test and bone formation in vivo in the animal bone implanting model. Our results supported discovered the antioxidant coating played the critical role one the success of bone related implants, which could be particularly noted in the future implant design. And the strategy applied here, utilizing the interactions between polyphenol and proteins to construct multilayer film, will pave the way to fabricating an antioxidant coating. [ABSTRACT FROM AUTHOR]

Abstract In this work, dimensionally stable Ti/SnO 2 -RuO 2 electrode is successfully prepared using thermal decomposition method for the electrocatalytic degradation of high-concentration industrial gallic acid (GA) effluent in detail. The surface morphology, crystal structure and element analysis of as-prepared Ti/SnO 2 -RuO 2 electrode are characterized by scanning electron microscopy, X-ray diffraction and X-ray fluorescence spectrometer, respectively. In addition, cyclic voltammetry, polarization curve and accelerated life tests are exploited to investigate the electrocatalytic activity and stability of Ti/SnO 2 -RuO 2 electrode. Orthogonal experiment shows that, among the factors (current density, temperature and initial pH), current density is pivotal parameter influencing the degradation efficiency of industrial GA effluent. COD removal and degradation efficiencies of GA effluent reach up to 76.9% and 80.1% after 6 h, respectively, at the optimal conditions (current density of 10 mA cm−2, pH 6 and 35 °C). The degradation of GA effluent follows pseudo-first-order reaction kinetics. This work provides an in-depth theoretical support and application of electrocatalytic technology to the treatment of high-concentration industrial GA effluent. Graphical abstract Image 1 Highlights • Dimensionally stable Ti/SnO 2 -RuO 2 anode is prepared by thermal decomposition method. • Ti/SnO 2 -RuO 2 anode exhibits higher oxygen evolution potential and better stability. • High-concentration industrial GA effluent is efficiently treated by Ti/SnO 2 -RuO 2 anode. • COD removal and degradation efficiencies of GA effluent reach to 76.9% and 80.1%. [ABSTRACT FROM AUTHOR]

Vascular diseases are the leading cause of morbidity and mortality worldwide and are urgently in need of diagnostic biomarkers and therapeutic strategies. Circular RNAs (circRNAs) represent a unique class of RNAs characterized by a circular loop configuration and have recently been identified to possess a wide variety of biological functions. CircRNAs exhibit exceptional stability, tissue specificity, and are detectable in body fluids, thus holding promise as potential biomarkers. Their encoding function and stable gene expression also position circRNAs as an excellent alternative to gene therapy. Here, we briefly review the biogenesis, degradation, and functions of circRNAs. We summarize circRNAs discovered in major vascular diseases such as atherosclerosis and aneurysms, with a particular focus on molecular mechanisms of circRNAs identified in vascular endothelial cells and smooth muscle cells, in the hope to reveal new directions for mechanism, prognosis and therapeutic targets of vascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Liu, Wang, Zhang, Fang and Meng.)

Purpose: This study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect., Methods: Here, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated., Results: These VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells., Conclusion: Together, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Tang, Jiang, Wang, Huang, Ding, Zhang, Li and Xie.)

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, is difficult to be targeted therapeutically due to negative expression of the bioreceptor, which leads to the poorest overall four-year survival rate among all cancer subtypes. We proposed that the nanomedicine featuring high payload and pH-responsive release of the loaded drugs could assist the TNBC treatment. In the present study, the His 6 -metal assemblies (HmA) were employed to encapsulate the doxorubicin (Dox), and the effect of HmA loaded with Dox (HmA@Dox) on treating TNBC was evaluated in vitro and in vivo. We found that the participation of Dox in the formation of HmA leads to high loading efficiency (99.4% for concentration ≤ 1 mg/mL) and the loading capacity (50.7% for concentration ≥ 10 mg/mL) of Dox encapsulated into HmA. HmA@Dox exhibited a narrow size distribution on the nanoscale, a pH-responsive release of loaded Dox, a quick endocytosis process, and fast lysosome escape. Most importantly, the HmA@Dox showed high efficacy in killing various breast cancer cells (MCF-7, MDA-MB-231, and MDA-MB-453) in vitro and depressing the development of TNBC in vivo. Our results demonstrated that such a strategy for designing a nanomedicine with high payload and responsive release of drugs to the environment around the tumor was of great importance to treat TNBC.

siRNA therapeutics as an emerging class of drug development is successfully coming to clinical utilization. The RNA-based therapy is widely utilized to explore the mechanism and cure a variety of gene-specific diseases. Tumor is an oncogene-driven disease; many genes are related to tumor progression and chemoresistance. Although human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody therapy has dramatically improved the survival rate, chemotherapy remains essential to HER2-positive (HER2+) breast cancer patients. Recently, X-box binding protein 1 (XBP1) has been involved in triple-negative breast cancer (TNBC) chemoresistance and progression, but its function in HER2+ breast cancer is poorly explored. Here, we silenced XBP1 expression using RNase-resistant RNA nanoparticles (NPs). Intravenous injection of RNA NPs with HER2-specific aptamers resulted in strong binding to tumors but not to healthy tissues. XBP1 deletion by RNA NPs impaired angiogenesis and inhibited cell proliferation, significantly suppressed breast cancer growth, and promoted the sensitization of chemotherapy in an HER2+ breast cancer mouse model. Overall, these results reveal the function of XBP1 in HER2+ breast cancer development and chemoresistance and imply that targeting XBP1 by RNA NPs may offer an easy and promising strategy for a combination treatment of breast cancer in the future.

Fully effective vaccines must induce both potent humoral and cellular immunities. Nanoparticles coencapsulating antigens and adjuvants have shown promising advantages as subunit vaccines in many aspects. However, the low loading efficiency and complicated synthesis process of these nanomaterials need to be improved. Here, we utilized hexahistidine (His 6 )-metal assembly (HmA) particles as carriers to codeliver ovalbumin peptides and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). We found that antigen/adjuvant-carrying HmA can efficiently enter into antigen-presenting cells and help the antigens escape from lysosomes to induce the maturation of these cells in vitro , characterized by increasing expression levels of costimulatory molecules and cytokines. More importantly, the vaccines with high biocompatibility can elicit strong humoral and cellular immunities by improving secretion of specific antibodies and cytokines, enhancing activation of DCs and T cells in vivo. Our results suggest that HmA provides a new approach for subunit vaccines by codelivery of antigens and adjuvants.

The phosphatase Cdc25A plays an important role in cell cycle regulation by dephosphorylating its substrates, such as cyclin-dependent kinases. In this study, we demonstrate that Cdc25A negatively regulates RIG-I-mediated antiviral signaling. We found that ectopic expression of Cdc25A in 293T cells inhibits the activation of beta interferon (IFN-β) induced by Sendai virus and poly(I·C), while knockdown of Cdc25A enhances the transcription of IFN-β stimulated by RNA virus infection. The inhibitory effect of Cdc25A on the antiviral immune response is mainly dependent on its phosphatase activity. Data from a luciferase assay indicated that Cdc25A can inhibit TBK1-mediated activation of IFN-β. Further analysis indicated that Cdc25A can interact with TBK1 and reduce the phosphorylation of TBK1 at S172, which in turn decreases the phosphorylation of its downstream substrate IRF3. Consistently, knockdown of Cdc25A upregulates the phosphorylation of both TBK1-S172 and IRF3 in Sendai virus-infected or TBK1-transfected 293T cells. In addition, we confirmed that Cdc25A can directly dephosphorylate TBK1-S172-p. These results demonstrate that Cdc25A inhibits the antiviral immune response by reducing the active form of TBK1. Using herpes simplex virus 1 (HSV-1) infection, an IFN-β reporter assay, and reverse transcription-quantitative PCR (RT-qPCR), we demonstrated that Cdc25A can also inhibit DNA virus-induced activation of IFN-β. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that Cdc25A can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we demonstrate that Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity. IMPORTANCE The RLR-mediated antiviral immune response is critical for host defense against RNA virus infection. However, the detailed mechanism for balancing the RLR signaling pathway in host cells is not well understood. We found that the phosphatase Cdc25A negatively regulates the RNA virus-induced innate immune response. Our studies indicate that Cdc25A inhibits the RLR signaling pathway via its phosphatase activity. We demonstrated that Cdc25A reduces TBK1 activity and consequently restrains the activation of IFN-β transcription as well as the antiviral status of nearby cells. We showed that Cdc25A can also inhibit DNA virus-induced activation of IFN-β. Taken together, our findings uncover a novel function and mechanism for Cdc25A in regulating antiviral immune signaling. These findings reveal Cdc25A as an important negative regulator of antiviral immunity and demonstrate its role in maintaining host cell homeostasis following viral infection., (Copyright © 2018 American Society for Microbiology.)

In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 3' untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 3' UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 3' UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.