Robust Covalent Organic Framework Photocatalysts for H2O2 Production: Linkage Position Matters.

Covalent organic frameworks (COFs) are promising photocatalysts for hydrogen peroxide (H2O2) synthesis. However, the nature of organic polymers makes the balance between high activity and stability challenging. We demonstrate that the linkage position matters in the design of robust COF photocatalysts with durable high activity without sacrificial reagents. COFs with ortho- and para-linkages (o-COFs and p-COFs) were constructed by 1,3,5-triformylphloroglucinol with benzene-, pyridine-, pyrazine-orthodiamines and paradiamines. The pyrzaine-containing o-COFs with two pyridinic nitrogen atoms exhibited a H2O2 production rate of 4396 µmol g-1 h-1 together with long-time continuous H2O2 photosynthesis performance in pure water (48 h), superior to the corresponding p-COFs. A four-step reaction mechanism is proposed by density function calculations. Moreover, the active sites and origin of stability enhancement for o-COFs are clarified. This work provides a simple and effective molecular design strategy in the design of robust COF photocatalysts for artificial H2O2 photosynthesis.

Prospective role of lusianthridin in attenuating cadmium-induced functional and cellular damage in rat thyroid.

The thyroid represents the most prevalent form of head and neck and endocrine cancer. The present investigation demonstrates the anticancer effects of Lusianthridin against cadmium (Cd)-induced thyroid cancer in rats. Swiss Wistar rats were utilized in this experimental study. Cd was employed to induce thyroid cancer, and the rats were divided into different groups, receiving oral administration of Lusianthridin (20 mg/kg) for 14 days. Thyroid parameters, deiodinase levels, hepatic parameters, lipid parameters, and antioxidant parameters were respectively estimated. The mRNA expression was assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Lusianthridin significantly (P < 0.001) improved protein levels, T4, T3, free iodine in urine, and suppressed the level of TSH. Lusianthridin significantly (P < 0.001) enhanced the levels of FT3, FT4, and decreased the level of rT3. Lusianthridin significantly (P < 0.001) reduced the levels of D1, D2, D3, and enhanced the levels of hepatic parameters like AST, ALT. Lusianthridin remarkably (P < 0.001) altered the levels of lipid parameters such as LDL, total cholesterol, HDL, and triglycerides; antioxidant parameters viz., MDA, GSH, CAT, and SOD. Lusianthridin significantly altered the mRNA expression of Bcl-2, Bax, MEK1, ERK1, ERK2, p-eIf2α, GRP78, eIf2α, and GRP94. The results clearly state that Lusianthridin exhibits protective effects against thyroid cancer.

The role of miR-222-2p in exosomes secreted by hexavalent chromium-induced premature senescent hepatocytes as a SASP component.

With the development of world industrialization, the environmental pollution of hexavalent chromium [Cr(VI)] is becoming an increasingly serious problem. In particular, the mechanisms by which long-term and low-dose exposure to Cr(VI) leading the development of related cancers are not well understood. As senescent cells gradually lose their ability to proliferate and divide, they will not be malignantly transformed. However, Senescence-associated secretory phenotype (SASP) released by senescent cells into the cellular microenvironment can act on neighboring cells. Since SASP has a bidirectional regulatory role in the malignant transformation of cells. Hence, It is very necessary to identified the composition and function of SASP which secreted by Cr(VI) induced senescent L02 hepatocytes (S-L02). Exosomes, a vesicle-like substances released extracellularly after the fusion of intracellular multivesicular bodies with cell membrane, are important components of SASP and contain a large number of microRNAs (miRNAs). By establishing Cr(VI)-induced S-L02 model, we collected the exosomes from the supernatants of S-L02 and L02 culture medium respectively, and screened out the highly expressed miRNAs in the exosomes of S-L02, namely the new SASP components. Among them, the increase of miR-222-5p was the most significant. It was validated that as SASP, miR-222-5p can inhibit the proliferation of L02 and S-L02 hepatocytes and at the same time accelerate the proliferation and migration ability of HCC cells. Further mechanistic studies revealed that miR-222-5p attenuated the regulatory effect of protein phosphatase 2A subunit B isoform R2-α (PPP2R2A) on Akt via repressing its target gene PPP2R2A, causing reduced expressions of forkhead box O3 (FOXO3a), p27 and p21, and finally increasing the proliferation of HCC cells after diminishing the negative regulation of on cell cycle. This study certainly provides valuable laboratory evidence as well as potential therapeutic targets for the prevention and further personalized treatment of Cr(VI)-associated cancers.

Ultrasound-triggered release of miR-199a-3p from liposome nanobubbles for enhanced hepatocellular carcinoma treatment.

This study was aimed to develop an efficient tumour-targeted liposome nanobubbles (LNBs) system using ultrasound-targeted nanobubble destruction for enhanced release and transfection of miRNA-199a-3p in hepatocellular carcinoma (HCC) therapy. The prepared LNBs comprised a polyethylene glycol-modified liposome shell and a perfluoropentane (PFP) core. MiRNA-199a-3p was attached to the nanocomposite surface via electrostatic adsorption, while RGD peptide functionalized the LNBs surface for enhanced HCC cell targeting, namely PFP@miR-RGD-LNBs. The LNBs were spherical with a narrow size distribution. The gene-loaded LNBs effectively condensed miR-199a-3p and protected it from enzymatic degradation. Low-intensity focused ultrasound (LIFU) promoted a fast release of miR-199a-3p from the prepared LNBs, thereby enhancing therapeutic effects. The combined application of PFP@miR-RGD-LNBs and LIFU exhibited a more potent inhibitory effect on HepG2 cells than the other groups, potentially due to LIFU promoting rapid and efficient gene release at the target site and increasing cell membrane permeability. Quantitative reverse transcription-polymerase chain reaction analysis revealed significantly increased mRNA expression levels of key apoptosis markers (Bad, Bax, Caspase-9 and Caspase-3) in the PFP@miR-RGD-LNBs + LIFU group compared to other groups. These findings suggest that the prepared LNBs are highly likely to be promising candidates for further exploration of HCC gene delivery and therapy.

Ambient NO2 hinders neutrophil extracellular trap formation in rats: Assessment of the role of neutrophil autophagy.

NO2 has been known to impair immunity and exacerbate susceptibility to infectious diseases. However, scant notice has been taken of the effect of NO2 on neutrophils. Neutrophil extracellular traps (NETs) formation is necessary for NETosis development by neutrophils as an immune system against pathogens. By analyzing the morphology and signature components of NETs, we focused for the first time on finding that 10 ppm of NO2 exposure for 15 consecutive days can hinder the formation of NETs. Next, we used NO2 in vivo derivatives to probe the mechanism for NETs formation in vitro. Our findings showed that NO2 suppression of respiratory burst levels and mitogen-activated protein kinase (MAPK)/Phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling was related to NO2 reduction in NETs formation. Inhibition of phorbol myristate acetate (PMA)-induced NETs formation by NO2 hindered autophagy, as evidenced by increased mTOR protein expression, decreased LC3 protein expression, and reduced autophagic vesicles. By activating mTOR-mediated autophagy, rapamycin (Rapa) reduced the inhibition of PMA-induced NETs by NO2. This study will provide valuable insights into the mechanisms of immunotoxicity of NO2, new insights into the etiology of diseases linked to NETs formation, and a theoretical basis for protection against such illnesses.

N-doped graphene aerogel cathode with internal aeration for enhanced degradation of p-nitrophenol by electro-Fenton process.

A columnar N-doped graphene aerogel (NGA) was successfully fabricated by one-step hydrothermal synthesis using L-hydroxyproline as reductant, N-doping, and swelling agent, and it was used as the cathode with internal aeration mode for the electro-Fenton degradation of p-nitrophenol. Owing to the stable solid-liquid-gas three-phase interface, more active defects, and modulated nitrogen dopants, the NGA cathode exhibited enhanced electrocatalytic activity. H2O2 could be continuously electro-generated via a two-electron oxygen reduction, and the yield of H2O2 was 153.3 mg·L-1·h-1 with the low electric energy consumption of 15.3 kWh kg-1. Simultaneously, the NGA cathode had better charge transfer capability with N-doping, which was conducive to the conversion of Fe3+/Fe2+. Under the optimal condition, nearly 100% removal of p-nitrophenol and 84% removal of TOC were obtained within 60 and 120 min, respectively. The NGA cathode also presented good stability and versatile applicability in different water matrices. Therefore, the NGA is a cost-effective cathode material in electro-Fenton system with adequate activity and reuse stabilization.

Effect of propiconazole on neutrophil extracellular traps formation: Assessing the role of autophagy.

Propiconazole (Pcz) is a kind of triazole fungicide which has an important impact on the environment. With the extensive use of Pcz in agricultural production activities, the pesticides are left in soil, water, crops and food, and will enter the organisms in the form of residues. Neutrophils play a key role in the body's innate immunity against pathogens, and the formation of neutrophil extracellular traps (NETs) is an important way for neutrophils to exert their immune function. In the present study, we focused on the effect of Pcz on the NETs of Sprague-Dawley (SD) rats for the first time. Our data demonstrated that Pcz could hinder NETs formation via inhibiting the Phosphoinositide 3-kinase (PI3K)/rapidly accelerated fibrosarcoma (Raf)/extracellular signal-regulated kinase (ERK) signaling. In the meanwhile, we assessed the role of autophagy played in this process and revealed that Pcz may inhibit the respiratory burst in neutrophils. This study provided new insights into the immunotoxic hazards of Pcz and additional laboratory evidence for assessing the impact of Pcz on terrestrial organisms.

The Ku70 -1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population.

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case-control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 -1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR=1.43, 95% CI=1.02-2.00, P=0.038 and OR=3.53, 95% CI=1.60-7.80, P=0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR=1.68, 95% CI=1.21-2.33, P=0.002), but not in postmenopausal women (OR=1.33, 5% CI=0.85-2.10, P=0.216). Our study suggests that the Ku70 -1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.