Investigation of the association between the Toll-like receptor 1 rs4833095 variation and gastric adenocarcinoma recurrence.

BACKGROUND: Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis. METHODS: We genotyped the TLR1 in 526 GC patients to investigate the association between the variation and gastric cancer survival by the multiplex polymerase chain reaction and sequencing method. The rs4833095 variation (chr4:38798089 [GRCh38. p14], T > C) in the TLR1 gene was genotyped in 526 patients who underwent GC resection. The associations between genotype, survival, and recurrence were investigated. The potential role of TLR1 in stomach cancer was investigated using clinical data from formalin-fixed, paraffin-embedded tissue samples. RESULTS: Patients with the T/C and C/C genotypes of rs4833095 had a lower risk of recurrence than those with the T/T genotype. Recurrence-free periods were substantially longer in patients with the T/C or C/C genotypes (22.6 and 22.3 months, respectively) than in those with the T/T genotype (20.7 months). Patients with the T/C or C/C genotype, low expression levels of VEGF1, high expression levels of ERBB2 and ERCC1, the absence of cancer nodules, a tumor size of less than 5 cm, and poor differentiation had a considerably reduced risk of recurrence. CONCLUSIONS: TLR1 rs4833095 was correlated with the postresection prognosis of patients with gastric cancer, suggesting that TLR1 may have a role in the onset or progression of gastric cancer.

Par3L, a polarity protein, promotes M1 macrophage polarization and aggravates atherosclerosis in mice via p65 and ERK activation.

Proinflammatory M1 macrophages are critical for the progression of atherosclerosis. The Par3-like protein (Par3L) is a homolog of the Par3 family involved in cell polarity establishment. Par3L has been shown to maintain the stemness of mammary stem cells and promote the survival of colorectal cancer cells. In this study, we investigated the roles of the polar protein Par3L in M1 macrophage polarization and atherosclerosis. To induce atherosclerosis, Apoe-/- mice were fed with an atherosclerotic Western diet for 8 or 16 weeks. We showed that Par3L expression was significantly increased in human and mouse atherosclerotic plaques. In primary mouse macrophages, oxidized low-density lipoprotein (oxLDL, 50 µg/mL) time-dependently increased Par3L expression. In Apoe-/- mice, adenovirus-mediated Par3L overexpression aggravated atherosclerotic plaque formation accompanied by increased M1 macrophages in atherosclerotic plaques and bone marrow. In mouse bone marrow-derived macrophages (BMDMs) or peritoneal macrophages (PMs), we revealed that Par3L overexpression promoted LPS and IFNγ-induced M1 macrophage polarization by activating p65 and extracellular signal-regulated kinase (ERK) rather than p38 and JNK signaling. Our results uncover a previously unidentified role for the polarity protein Par3L in aggravating atherosclerosis and favoring M1 macrophage polarization, suggesting that Par3L may serve as a potential therapeutic target for atherosclerosis.

Hypoxia induces hepatocellular carcinoma metastasis via the HIF-1α/METTL16/lnc-CSMD1-7/RBFOX2 axis.

Hypoxic microenvironment is clinically associated with metastasis and poor prognosis of numerous cancers. The mechanisms by which intratumoral hypoxia regulates metastasis are not fully understood. Our study identifies a downregulation of Lnc-CSMD1-7 in hepatocellular carcinoma (HCC) and correlated with poor prognosis of HCC patients. Lnc-CSMD1-7 negatively regulated HCC cell migration and invasion in vitro and suppressed lung metastasis in vivo. Mechanistically, Lnc-CSMD1-7 directly binds to RBFOX2, thereby affecting RBFOX2-regulated alternative splicing in epithelial and mesenchymal-specific events. More importantly, hypoxic microenvironment and m6A methylation mediate the downregulation of Lnc-CSMD1-7 expression. Specifically, hypoxia transcriptionally upregulates the expression of the m6A methyltransferase METTL16 via HIF-1α, and METTL16 directly binds to Lnc-CSMD1-7 and downregulates the RNA stability of Lnc-CSMD1-7 via m6A methylation, ultimately promoting HCC metastasis. Our findings highlight the regulatory function of the METTL16/Lnc-CSMD1-7/RBFOX2 axis in modulating hypoxia-induced HCC progression, which may provide potential prognostic and therapeutic targets for HCC treatment.

NiO-NiMoO4 Nanocomposites on Multi-Walled Carbon Nanotubes as Efficient Bifunctional Electrocatalysts for Total Water Splitting.

Multicomponent synergistic regulation and defect design have been effective strategies to enhance the electrocatalytic activity of transition-metal oxides. In this work, NiO and NiMoO4 nanocomposites on multi-walled carbon nanotubes (termed NiO-NiMoO4/mCNTs) are synthesized through a two-step method. Physical characterizations show NiO-NiMoO4/mCNTs have a well-defined NiO-NiMoO4 structure, large specific surface area, and abundant oxygen vacancies. For oxygen evolution reaction (OER), NiO-NiMoO4/mCNTs deliver lower overpotential (277 mV) than NiO/mCNTs, NiO, and commercial RuO2 nanocrystals at 10 mA cm-2. For hydrogen evolution reaction (HER), NiO-NiMoO4/mCNTs still show the best HER activity, manifested by the smallest onset potential and the lowest Tafel. Density functional theory calculations show that the adsorption energies of hydrogen- and oxygen-containing intermediates on the NiO-NiMoO4/mCNTs surface have changed, which can lower the energy barriers required for HER and OER. The excellent electrocatalytic activity of bifunctional NiO-NiMoO4/mCNTs for OER and HER can be attributed to the synergy effect between NiO, NiMoO4, and mCNTs. A symmetrical two-electrode water electrolyzer with NiO-NiMoO4/mCNTs as both the cathode and anode are constructed, which can reach a current density of 10 mA cm-2 and only requires 1.57 V.

The Effects of a High-Fat Diet on Inflammatory Bowel Disease.

The interactions among diet, intestinal immunity, and microbiota are complex and play contradictory roles in inflammatory bowel disease (IBD). An increasing number of studies has shed light on this field. The intestinal immune balance is disrupted by a high-fat diet (HFD) in several ways, such as impairing the intestinal barrier, influencing immune cells, and altering the gut microbiota. In contrast, a rational diet is thought to maintain intestinal immunity by regulating gut microbiota. In this review, we emphasize the crucial contributions made by an HFD to the gut immune system and microbiota.

Kazinol B protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced cardiac injury by modulating the AKT/AMPK/Nrf2 signalling pathway.

CONTEXT: Kazinol B (KB), an isoprenylated flavan derived from Broussonetia kazinoki Sieb. (Moraceae) root, has long been used in folk medicine. OBJECTIVE: This study examines the protective effects of KB and its underlying mechanisms in hypoxia and reoxygenation (H/R)-induced cardiac injury in H9c2 rat cardiac myoblasts. MATERIALS AND METHODS: H9c2 cells were incubated with various concentrations of KB (0, 0.3, 1, 3, 10 and 30 µM) for 2 h and then subjected to H/R insults. The protective effects of KB and its underlying mechanisms were explored. RESULTS: KB significantly elevated cell viability (1 µM, 1.21-fold; 3 µM, 1.36-fold, and 10 µM, 1.47-fold) and suppressed LDH release (1 µM, 0.77-fold; 3 µM, 0.68-fold, and 10 µM, 0.59-fold) in H/R-induced H9c2 cells. Further, 10 µM KB blocked apoptotic cascades, as shown by the Annexin-V/PI (0.41-fold), DNA fragmentation (0.51-fold), caspase-3 (0.52-fold), PARP activation (0.27-fold) and Bax/Bcl-2 expression (0.28-fold) assays. KB (10 µM) downregulated reactive oxygen species production (0.51-fold) and lipid peroxidation (0.48-fold); it upregulated the activities of GSH-Px (2.08-fold) and SOD (1.72-fold). KB (10 µM) induced Nrf2 nuclear accumulation (1.94-fold) and increased ARE promoter activity (2.15-fold), HO-1 expression (3.07-fold), AKT (3.07-fold) and AMPK (3.07-fold) phosphorylation. Nrf2 knockdown via using Nrf2 siRNA abrogated KB-mediated protective effects against H/R insults. Moreover, pharmacological inhibitors of AKT and AMPK also abrogated KB-induced Nrf2 activation and its protective function. DISCUSSION AND CONCLUSIONS: KB prevented H/R-induced cardiomyocyte injury via modulating the AKT and AMPK-mediated Nrf2 induction. KB might be a promising drug candidate for managing ischemic cardiac disorders.

Does Education Influence Life-Course Depression in Middle-Aged and Elderly in China? Evidence from the China Health and Retirement Longitudinal Study (CHARLS).

Mental health problems have become a major public health problem worldwide and are more common among middle-aged and elderly people in China. Research on the effect of education on depression is limited, and whether the relationship between education and depression changes over the life course remains unclear. This study was based on the cross-sectional data of 15,767 middle-aged and elderly individuals in the 2018 tracking survey (Wave 4) of the China Health and Retirement Longitudinal Study (CHARLS) database. Multiple linear regression and bootstrap methods were developed to detect the mediating effect of education on depression. In all samples or different age groups, education was significantly positively associated with depression. Three mediators (economic level, health-related lifestyle, and cognitive level) were significantly positively associated with depression, and cognitive level had a greater effect on depression than economic level and health-related lifestyle. The total, direct, and indirect effects of the whole samples and elderly samples were significant; however, the direct effect of the middle-aged samples was insignificant, and the total and indirect effects of the three mediating pathways were all significant, that is, economic level, health-related lifestyle, and cognitive level should produce complete mediation. The multiple linear regression and bootstrap methods could successfully detect the mediating effect of education on depression. On the basis of the education, economic level, health-related lifestyle, cognitive level, and depression of middle-aged and elderly people, we established and compared the total, direct, and mediating effects of education on depression under the life course. The mediating variables should be further increased, and the measurement methods of depression should be developed to improve the credibility of the research results.

Clinical and functional characterisation of the SMAD4 germline variant c.1035C > A in a family with juvenile polyposis syndrome by whole-exome sequencing.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant inherited disease characterised by multiple juvenile polyps. Genes with JPS-associated mutations and their correlation with the phenotype are currently unknown. Gastrointestinal endoscopy results of a 31-year-old female patient showed multiple polyps in the digestive tract, and the presence of juvenile polyps was confirmed by pathological examination. During follow-up, the patient underwent total gastrectomy and polypectomy several times. Five members of this family were diagnosed with JPS, of which two died and three survived. Full exon gene sequencing of eight members of this family revealed a SMAD4 (NM-005359.3) c.1035C > A (p.Cys345*) mutation. This mutation leads to premature codon termination, causing protein truncation. SMAD4 is a pathogenic gene associated with JPS. This is the first report of an association between the c.1035C > A mutation and JPS pathogenesis. Detection of JPS-related mutations in family members with a genetic predisposition for JPS is very important for genetic counselling, surgical intervention, long-term monitoring and follow-up, and drug treatment.

A self-circulating electro-fenton-like process over Fe3O4-CaO2 cathode for highly efficient degradation of levofloxacin.

Electro-Fenton reaction was limited by the generation of H2O2 and the circulation of Fe(Ⅱ)/Fe(Ⅲ). Herein, an efficient electro-Fenton-like process was constructed based on Fe3O4-CaO2 cathode promoted by peroxymonosulfate (PMS). Levofloxacin (LEV) could be efficiently degraded (92.1%) and mineralized with the TOC removal of 74.5% in this self-circulating process. More importantly, the Fe3O4-CaO2 exhibited good stability in the recycles due that CaO2 was covered by Fe3O4, which inhibited the rapid release of H2O2. Mechanism analysis indicated that CaO2 could not only replace H2O2 to accelerate the oxidation of Fe(Ⅱ) to Fe(Ⅲ), but also could form complexes with Fe(Ⅲ) and PMS to transfer electrons from ligands to metals, thereby enhancing the reduction of Fe(Ⅲ) to Fe(Ⅱ). As a result, the electrical consumption was significantly reduced, which was only 5.0% of the Fe3O4 in electro-Fenton reaction. Meanwhile, the hydrolyzed product of Ca(OH)2 reacted with Fe(Ⅲ) in the presence of H2O2 and converted into CaO2. Thus, the self-circulation of CaO2/Ca(OH)2 and Fe(Ⅲ)/Fe(Ⅱ) was realized, which accelerated the generation of active species, such as, ·OH, O2·- and 1O2. This work first proposed a self-circulating electro-Fenton-like system and demonstrated the potential application of Fe3O4-CaO2 in the treatment of wastewater.

Improving Innovation and Access to Combination Vaccines for Childhood Immunization in China.

BACKGROUND: combination vaccines can improve timely vaccination coverage and mitigate the social and economic burdens of both caregivers and health systems. Compared to other countries with high immunization performance, China remains behind the curve in promoting the inclusion of new combination vaccines into national vaccination schedules. The domestic research and development pipeline faces many technical obstacles, regulatory pressures, and competitive opposition. In addition to this, health disparities regarding combination vaccines exist in each dimension of access and their determinants, including availability, accessibility, acceptability, and quality. Our study aims to provide a cross-disciplinary analysis of China's combination vaccines (from innovation to access) and identify the main factors that affect the attitudes and behavior choices for combination vaccines. METHOD: systematic reviews and secondary data analysis will be conducted to map the landscape of combination vaccines in China and the determinants influencing their innovation and access. A cross-sectional survey will be performed in seven provinces of China based on geo-economic representativeness among caregivers with children that are between 2 and 24 months old and are registered in the national immunization system. Questionnaires will be used to examine the relationship between each dimension of access and their determinants. These questionnaires will cover the caregivers' knowledge, attitude, and willingness to pay for combination vaccines, as well as their perceptions about vaccination services. Semi-structured interviews with the suppliers (public and private) and healthcare providers will help identify research gaps and the key challenges they face when developing and introducing combination vaccines in China. DISCUSSION: using a combined approach, with cross-country and multi-disciplinary support from experts, our research is designed to fill the information gaps in China's combination vaccine industry across the innovation-access spectrum. It will lead to evidence-based recommendations which will foster greater access to innovation-enhancing combination vaccines for childhood immunization in China. Moreover, the multi-dimensional approach could also be adapted beyond combination vaccines to assess innovation and other public goods for health among disadvantaged groups in the future.

An Ultrasensitive Electrochemical Biosensor Integrated by Nicking Endonuclease-Assisted Primer Exchange Reaction Cascade Amplification and DNA Nanosphere-Mediated Electrochemical Signal-Enhanced System for MicroRNA Detection.

Specific and sensitive microRNAs (miRNAs) detection is essential to early cancer diagnosis. The development of these technologies including functional nuclease-mediated target amplification and DNA nanotechnology possesses tremendous potential for the high-performance detection of miRNAs in the accurate diagnosis of disease. In this study, we have established an ultrasensitive electrochemical biosensor by combining nicking endonuclease-assisted primer exchange reaction (PER) cascade amplification with a DNA nanosphere (DNS)-mediated electrochemical signal-enhanced system for the detection of miRNA-21 (miR-21). The cascade amplification is initiated by a nicking endonuclease that can cleave specific DNA substrates and highly amplify translation of the target to single-stranded DNA fragments (sDNA). Then, the PER cascade is powered by strand-displacing polymerase and generates a large amount of nascent single-stranded connector DNA (cDNA) via sDNA triggering of the dumbbell probe (DP), thus achieving the cascade amplification of the target. Finally, the DNS loaded with plenty of electroactive substances can be captured on the electrode via cDNA for further enhancing the electrochemical signal and highly sensitive detection of miR-21. The proposed electrochemical biosensor exhibits a wide detection range of 1 aM to 0.1 nM and a low detection limit of 0.58 aM. The excellent selectivity allows the biosensor to discriminate miR-21 from other miRNAs, even the one base-mismatched sequence. Moreover, the practicability of the biosensor is investigated by analyzing miR-21 in human serum and cancer cell lysate. Therefore, our proposed nicking endonuclease-assisted PER cascade amplification strategy provides a powerful platform for the early detection of miRNA-related disease and molecular diagnosis.

A proteomic and RNA-seq transcriptomic dataset of capsaicin-aggravated mouse chronic colitis model.

An inappropriate diet is a risk factor for inflammatory bowel disease (IBD). It is established that the consumption of spicy food containing capsaicin is strongly associated with the recurrence and worsening of IBD symptoms. Moreover, capsaicin can induce neutrophil accumulation in the lamina propria, contributing to disease deterioration. To uncover the potential signaling pathway involved in capsaicin-induced relapse and the effects of capsaicin on neutrophil activation, we performed proteomic analyses of intestinal tissues from chronic colitis mice following capsaicin administration and transcriptomic analyses of dHL-60 cells after capsaicin stimulation. Collectively, these multiomic analyses identified proteins and genes that may be involved in disease flares, thereby providing new insights for future research.

A carbon dots-enhanced laccase-based electrochemical sensor for highly sensitive detection of dopamine in human serum.

Enzyme-based electrochemical sensor possesses a significant advantage in the highly efficient detection of small molecules, however, the poor electron transport efficiency limits their wide application. In this study, taking advantage of the distinct biocatalytic activity of laccase and the excellent electroconductibility of carbon dots, a carbon dots-enhanced laccase-based electrochemical sensor for the detection of dopamine (DA) is established. Thereinto, laccase can specifically recognize DA and promote its electrocatalytic oxidation on the electrode, while, the carbon dots can be used as the immobilization substrate of laccase and enhance its electron transfer efficiency, thus achieving the highly sensitive detection of dopamine. The electrochemical performance of the modified electrode interface is studied by electrochemical impedance spectroscopy and differential pulse voltammetry. As demonstrated, the electrocatalytic activity of the proposed electrochemical sensor for DA is significantly improved and exhibits a low detection limit (0.08 µM) and a wide linear range (0.25 µM-76.81 µM). The excellent selectivity allows the sensor has the capacity for specific discrimination the DA from other interferents. Furthermore, by analyzing the DA in human serum verifies the practicability of this assay in real sample analysis.

Rapid fabrication of bionic pyrogallol-based self-adhesive hydrogel with mechanically tunable, self-healing, antibacterial, wound healing, and hemostatic properties.

Hydrogels are functional materials that are similar to human skin and have received much attention in recent years for biomedical applications. However, the preparation of nontoxic, highly adhesive, and antimicrobial hydrogels in an efficient way remains a great challenge. Inspired by adhesive mussel foot proteins (mfps) which consist of abundant catecholic amino acids and lysine (Lys) residues, gallic acid-modified ε-poly-L-lysine (EPL/GA) was synthesized, and an active functional monomer (AA-EPL/GA) was then created through a reaction with acrylic acid (AA). The polymerization of AA-EPL/GA occurred rapidly (30-160 s) under blue light (λ = 405 nm) irradiation to produce a biomimetic PAA-EPL/GA hydrogel under mild conditions. The biomimetic pyrogallol-Lys distribution endowed the PAA-EPL/GA hydrogels with superior adhesion in humid environments (with an adhesive strength of 50.02 kPa toward wet porcine skin) and tunable mechanical and self-healing properties. Additionally, the PAA-EPL/GA hydrogels exhibited outstanding antibacterial ability due to the inherent characteristics of GA and EPL. In a mouse model, PAA-EPL/GA adhered firmly around the wound tissues. Photographs of the wound and the histological results demonstrated the ability of the hydrogel to promote wound healing, control wound infection, and suppress scar formation. Moreover, the hydrogel had a good hemostatic effect on liver bleeding. Our results highlighted the promising application potential of GA-based hydrogels, which were easily, harmlessly, and efficiently fabricated by blue light irradiation.

Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis.

Crohn's disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.

Membrane-Active Antibacterial Agents Based on Calix[4]arene Derivatives: Synthesis and Biological Evaluation.

Bacteria have developed increasing resistance to currently used antimicrobial agents. New classes of antimicrobial drugs are urgently required to fight drug-resistant pathogens. Here, we designed and synthesized a series of calix[4]arene derivatives as antibacterial agents by biomimicking the structural properties and biological functions of antibacterial peptides. After introducing cationic hydrophilic moieties and preliminary structural optimization, we obtained a lead compound (16) that exhibited excellent antibacterial activity against Gram-positive bacteria, low toxicity toward mammalian cells and poor hemolytic activity. The antibacterial mechanism studies showed that compound 16 can destroy bacterial cell membrane directly, leading to bacterial death and a low tendency to develop bacterial resistance.

A novel electrochemically enhanced homogeneous PMS-heterogeneous CoFe2O4 synergistic catalysis for the efficient removal of levofloxacin.

A novel electrochemically enhanced homogeneous-heterogeneous catalytic system was constructed by placing the prepared heterogeneous catalyst (CoFe2O4/NF) in parallel between the anode and the cathode for peroxymonosulfate (PMS) activation to remove levofloxacin (LVF) in this work. Over 90% of LVF could be effectively removed by the constructed system after 40 min's degradation. And the electrical energy consumption was only 2.51 kWh/m3, which was lower than 54.5% of the traditional electrochemical advanced oxidation process. Besides, the system broadened the response range of pH and overcame the inhibitory effect of alkaline conditions on degradation. These activities were mainly due to the high generation ability of free radical (SO4·-, ·OH and O2·-) and non-radical (1O2). And the SO4·- was found to be the main radical for LVF degradation. The high SO4·- generation ability was demonstrated to be resulted from the dual effects of synergy of CoFe2O4/PMS and enhancement of electrochemistry in EC/CoFe2O4/PMS system. In detail, electrochemistry could effectively promote the continuous circulation of Co2+/Co3+ and Fe2+/Fe3+ redox cycles on the surface of CoFe2O4 to enhance the activation of PMS, thereby generating SO4·-. This work can provide a promising and cost-effective approach to construct highly efficient organic pollutant degradation system.

Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: inhibition of macrophage inflammation.

Despite improvements in cardiovascular disease (CVD) outcomes by cholesterol-lowering statin therapy, the high rate of CVD is still a great concern worldwide. Dehydrocorydaline (DHC) is an alkaloidal compound isolated from the traditional Chinese herb Corydalis yanhusuo. Emerging evidence shows that DHC has anti-inflammatory and antithrombotic benefits, but whether DHC exerts any antiatherosclerotic effects remains unclear. Our study revealed that intraperitoneal (i.p.) injection of DHC in apolipoprotein E-deficient (ApoE-/-) mice not only inhibited atherosclerosis development but also improved aortic compliance and increased plaque stability. In addition, DHC attenuated systemic and vascular inflammation in ApoE-/- mice. As macrophage inflammation plays an essential role in the pathogenesis of atherosclerosis, we next examined the direct effects of DHC on bone marrow-derived macrophages (BMDMs) in vitro. Our RNA-seq data revealed that DHC dramatically decreased the levels of proinflammatory gene clusters. We verified that DHC significantly downregulated proinflammatory interleukin (IL)-1ß and IL-18 mRNA levels in a time- and concentration-dependent manner. Furthermore, DHC decreased lipopolysaccharide (LPS)-induced inflammation in BMDMs, as evidenced by the reduced protein levels of CD80, iNOS, NLRP3, IL-1ß, and IL-18. Importantly, DHC attenuated LPS-induced activation of p65 and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Thus, we conclude that DHC ameliorates atherosclerosis in ApoE-/- mice by inhibiting inflammation, likely by targeting macrophage p65- and ERK1/2-mediated pathways.

Tannic acid reinforced electro-Fenton system based on GO-Fe3O4/NF cathode for the efficient catalytic degradation of PNP.

In order to overcome the sluggish kinetics of the redox conversion between Fe3+ and Fe2+ in Fenton process, we established a novel electro-Fenton system based on GO-Fe3O4 cathode and tannic acid (TA) for the efficient degradation of p-nitrophenol (PNP). Under the optimal degradation parameters (including the initial PNP concentration of 20 mg L-1, pH = 5, current density of 30 mA cm-2 and feeding ratio of PNP: TA = 1:2), the TA reinforced GO-Fe3O4 electro-Fenton system exhibited the removal rate of PNP over 90.1 ± 0.2%, the COD removal rate of 69.5 ± 0.84% and satisfactory reusability (with the removal rate of ∼80% after 5 recycles). The excellent degradation performance of the proposed TA reinforced GO-Fe3O4 electro-Fenton system was partly attributed to the optimized morphology (with the particle size of Fe3O4 reduced to tens of nanometers, pore size decreased by ∼80% and pore volume increased by 24.3 times) and larger specific surface area (increased by 72.7 times) after compositing GO with Fe3O4, which exposed more active sites. In return, the electron transfer process, the two-electron oxygen reduction reaction (ORR) and the degradation efficiency were promoted in the cooperation of GO and Fe3O4. Moreover, the incorporated TA would form a TA-Fe(III) complex to promote the reduction reaction from Fe3+ to Fe2+, which strengthened the self-circulation of Fe2+ and Fe3+ and indirectly enhanced the conversion of H2O2 to ROS to decompose PNP into smaller organic fragments or mineralize into CO2, H2O, NO2- or NO3-, etc. Obviously, the incorporation of TA provided a promising strategy to improve the electro-Fenton efficiency and realize the efficient removal of PNP in wastewater.

Commentary on: Screening of immunosuppressive cells from colorectal adenocarcinoma and identification of prognostic markers.

Colorectal adenocarcinoma (COAD) is one subtype of colorectal carcinoma (CRC), whose development is associated with genetics, inappropriate immune response, and environmental factors. Although significant advances have been made in the treatment of COAD, the mortality rate remains high. It is a pressing need to explore novel therapeutic targets of COAD. Available evidence indicated that immune cell infiltration was correlated with cancer prognosis. To reveal the roles of immune cells in the COAD prognosis, a study published in Bioscience Reports by Li et al. (Bioscience Reports (2021) 41, https://doi.org/10.1042/BSR20203496) analyzed data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. It demonstrated a beneficial effect of Th17 cells in COAD prognosis. In addition, six hub genes (KRT23, ULBP2, ASRGL1, SERPINA1, SCIN, and SLC28A2) were identified to correlate with Th17 cells and COAD prognosis, suggesting one new therapy strategy and some predictive biomarkers of COAD. These findings reported by Li et al. may pave one way to explore the molecular mechanism of COAD further.