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The balance between inflammatory T helper type 17 (Th17) and immunosuppressive regulatory T (Treg) cells is critical for maintaining immune homeostasis in the human body and is tightly regulated under healthy conditions. An increasing number of studies have reported that deubiquitinases (DUBs) play a vital role in regulating Th17- and Treg-cell differentiation. However, the biological functions of only a small fraction of DUBs in Th17- and Treg-cell differentiation are well defined. In this study, we identified ubiquitin-specific peptidase 1 (USP1) as a vital regulator of CD4

Background: The authors investigated a panel of novel biomarkers for diagnosis and prognosis assessment of sepsis using machine learning (ML) methods. Methods: Hematological parameters, liver function indices and inflammatory marker levels of 332 subjects were retrospectively analyzed. Results: The authors constructed sepsis diagnosis models and identified the random forest (RF) model to be the most optimal. Compared with PCT (procalcitonin) and CRP (C-reactive protein), the RF model identified sepsis patients at an earlier stage. The sepsis group had a mortality rate of 36.3%, and the RF model had greater predictive ability for the 30-day mortality risk of sepsis patients. Conclusion: The RF model facilitated the identification of sepsis patients and showed greater accuracy in predicting the 30-day mortality risk of sepsis patients.

The relative abundance of myeloid-derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin-specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)-MDSCs, resulting in increased CD8

Background Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. Methods One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman’s correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. Results Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. Conclusions The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

Heterogeneous catalytic ozonation (HCO) was a promising water purification technology. Designing novel metal-based catalysts and exploring their structural-activity relationship continued to be a hot topic in HCO. Herein, we reviewed the recent development of metal-based catalysts (including monometallic and polymetallic catalysts) in HCO. Regulation of metal based active sites (surface hydroxyl groups, Lewis acid sites, metal redox cycle and surface defect) and their key roles in activating O

In this study, CeOx with different exposed facets was prepared to investigate their potential effect on activating the peroxone reaction (H2O2/O3) and breaking through the restriction of solution pH on peroxone. By controlling the concentration of hydroxide, cube CeOx with a (100) facet, rod CeOx with a (110) facet and octahedron CeOx with a (111) facet were prepared by the hydrothermal precipitation method, and they all promoted heterogeneous peroxone for oxalic acid (OA) under acidic conditions. The catalytic activity of CeOx was highly related to their surface oxygen vacancies (OVs) and the interfacial electron transfer process. Both experiments and theoretical calculations showed that CeOx with different exposed facets activated peroxone in different ways and (111) CeOx possessed better activity than (100) or (110) CeOx. The low efficiencies of (100) and (110) CeOx were due to their inefficient use of H2O2 to reduce surface Ce4+ and their large energy gap to generate surface peroxide (OVs-OOH). (111) CeOx was stable with surface-adsorbed H2O2, and the rich electrons at OVs could be donated to H2O2 and generate OVs-OOH, which then triggered O3 decomposition into hydroxyl radical (˙OH) and superoxide radical (˙O2−). These electron migration processes depended on the electron-donating ability of the OVs rather than solution pH, therefore, still greater amounts of reactive species were generated under acidic conditions. The flexibility of the (111) CeOx/H2O2/O3 process was further investigated for removing 20 kinds of pharmaceuticals. The synergy effect of (111) CeOx/O3 and H2O2 varied with the structure of the pharmaceuticals.

A new β-cyclodextrin-bonded chiral stationary phase (TCDP) with a thiocarbamated benzamide spacer was prepared and evaluated on HPLC by separating a series of chiral pesticides and drugs. TCDP resolved all 24 analytes (11 triazoles, 8 flavanones and 5 β-blockers), and 18 of them were completely separated. The enantioresolution ranges were 1.45 - 3.33 for triazoles, 0.35 - 2.45 for flavanones and 1.26 - 1.58 for β-blockers. Among them the best resolution of tebuconazole was up to 3.33 within 13 min. Bitertanol (two chiral centers) and triticonazole with cis/trans isomers were separated into four peaks, respectively. TCDP could also completely resolve myclobutanil (Rs = 1.68), which was difficult to be separated on other CD-CSPs. Common CDSP only resolved a few analytes. The results showed that the thiocarbamated benzamide spacer of TCDP may provide a synergistic effect of hydrogen bonding and coordination. The spacer deserved full utilization, by which may avoid troublesome derivatization at low cost.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti‐inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti‐inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine‐1‐phosphate (S1P) in a S1P lyase (SPL)‐dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro‐inflammatory cytokines by suppressing nuclear factor‐κB and mitogen‐activated protein kinases signalling pathways. Furthermore, vitamin B6–reduced accumulation of S1P by promoting SPL activity. The anti‐inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti‐inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

A mono-6-(4-nitrophenyl)-ureido-β-cyclodextrin-bonded chiral stationary phase (NCDSP), containing π-electron withdrawing groups, was prepared by immobilizing a self-prepared mono-6-(4-nitrophenyl)-...

Monocyte distribution width (MDW) is a blood monocyte morphological parameter that can be easily detected by an automated hemocyte analyzer and can provide clinicians with important information about cell volume variability in peripheral blood monocyte populations. The United States' Food and Drug Administration and Conformite Europeenne have both been cleared for their clinical application in the detection of sepsis and developing sepsis in adult patients in the emergency department (ED). Recently, MDW has been found to have an early diagnosis and predictive value for sepsis in neonates and COVID-19 patients. Here, we summarize the findings of the studies investigating the clinical application of MDW in sepsis. Under different stimuli, especially in infectious diseases, the activation of innate immunity is the host's first defense mechanism, and the change in monocyte volume is considered an early indicator reflecting the state of activation of innate immunity. Pivotal study data from a large multicenter patient cohort showed that abnormal MDW at presentation increases the odds of sepsis, considering the combination of MDW and White Blood Cell Count (WBC) as part of a standard sepsis assessment protocol for ED, which may increase the sensitivity and specificity of sepsis diagnosis. Meanwhile, MDW shares a diagnostic performance comparable to that of conventional biomarkers (C-reactive protein and procalcitonin) in sepsis. In addition, some evidence suggests that increased MDW, both in adults and neonates, may be associated with unfavorable short- and long-term outcomes, which indicates its prognostic value in sepsis. Taken together, MDW is a parameter of increased morphological variability of monocytes in response to infection, and numerous studies have shown that MDW could be used as a valuable diagnostic and prognostic index in patients with sepsis or suspected sepsis.

A large π-conjugated perylenediimide bridged bis(β-cyclodextrin)-bonded stationary phase (PBCDP) was first prepared and characterized. The chiral HPLC performance was systematically evaluated using a series of chiral probes. The results showed that PBCDP could resolve 36 kinds of chiral compounds in reversed-phase and polar organic modes with high resolutions (Rs) 1.48-3.28 for profens, 1.25-2.85 for triazoles, 1.34-5.29 for flavanones, 1.66-4.58 for amino acids and 1.22-1.97 for β-blockers. Especially, PBCDP could completely resolve acidic non-steroidal chiral drugs (profens) and simultaneously resolve basic five triazole pesticides, which were difficult to separate by ordinary CDCSP. Compared with CDCSP (15 kinds), the new stationary phase has a wider resolution range (36 kinds). Obviously, the synergistic inclusion of the two cavities of bridged cyclodextrin, as well as the large π-π stacking, hydrogen bond, dipole-dipole and basic primary amine site (-NH-) provided by the perylenediimide bridging group contributed together to the improvement of the above chiral separations. PBCDP was a new type of versatile chiral separation material without port derivatization.

In this study, reduced graphene oxide (rGO) was used to fabricate a Z-scheme BiVO

An azobenzenediamide bridged bis(β-cyclodextrin) chiral stationary phase (AZCDP) was prepared, and its high-performance liquid chromatography performance in reversed-phase and polar organic modes was evaluated by chiral probes, including triazoles, flavanones, amino acids and β-blockers. The results showed that AZCDP had strong chiral separation ability and the 40 chiral compounds were successfully resolved, of which 32 were completely separated (Rs ≥ 1.5) and the best enantioresolution was up to 3.93 within 20 min under a wide range of pH value and temperature. The separation ability of AZCDP with double cavities was significantly better than common CD-CSPs with single cavity, which was related to the synergistic inclusion effect. Compared with the previously reported stilbene (C=C)-bridged CSP, AZCDP with azobenzene (N=N)-bridged had a wider resolution range. For example, it could resolve myclobutanil, pindolol, carteolol, betaxolol, bevanolol and bitertanol, which could not be resolved before, and should be related to the fact that the flexible N=N was more compatible with the synergistic inclusion between cavities than the rigid C=C bridge group. The azobenzenediamide bridging group could also provide hydrogen bond, π–π and other sites, which was conducive to chiral separations.

Single atomic Cu catalysts (SACs Cu@C) anchored by carbon skeleton and chlorine atom was synthesized by hydrolyzing Cu-MOFs and then pickled by aqua-regia to remove Cu nanoparticles (NPs Cu). Comparative characterizations revealed that SACs Cu@C was a hierarchically porous nanostructure and Cu dispersed uniformly throughout the carbon skeletons. With less active components, SACs Cu@C behaved better in activating PMS over NPs Cu@C on ibuprofen removal (91.3 % versus 30.2 % in 30 min). Two Cu coordination environments were found by EXAF and DFT calculation, including four-coordinated Cu with 4C atoms and six-coordinated Cu with 4Cu and 2Cl atoms. The obvious interfacial electron delivery between PMS and SACs Cu@C was found, which was enhanced by Cl atom. Cu(I)/Cu(II) redox cycle would donate electron to peroxy bond of PMS for generating OH, SO

N vacancies, hydrophobic sites and electron rich zone were simply regulated by doping F into g-C

The vast majority of current structural design codes and standards do not separately consider the wind and turbulence profiles for different storm types. Based on the 356-m-high Shenzhen Me...

A cholesterol mono-derivatized β-cyclodextrin was synthesized and bonded onto silica gel (SBA-15) to obtain a cholesterol mono-derivatized β-cyclodextrin-bonded stationary phase (CHCDP). The chemical structures of mono-derivatized β-cyclodextrin and CHCDP were characterized by infrared spectroscopy, mass spectrometry, elemental analysis and thermogravimetric analysis, correspondingly. Furthermore, the separation ability of CHCDP in terms of achiral compounds was systematically evaluated by separating benzene homologs, polycyclic aromatic hydrocarbons (PAHs) and some positional isomers. As a result, CHCDP completely separated five benzene homologs and nine PAHs within 30 min under the reversed-phase. In addition, the chiral chromatographic property of CHCDP was also evaluated by separating some racemic compounds including flavanones, triazoles, β-blockers, etc. The results showed that the CHCDP exhibited high enantioselectivities towards most of selected analytes. The enantioresolutions were in the range from 1.43 to 2.51 on CHCDP. Especially the resolutions of 2'-hydroxyflavanone, hexaconazole, Dns-serine and atenolol were as high as 1.94, 1.91, 2.15 and 1.57, respectively. Obviously, the CHCDP was a versatile stationary phase with chiral and achiral separation capabilities in multi-mode chromatography, which was related to the introduction of cholesterol to the port of cyclodextrin, enhancing the hydrophobic interaction of cyclodextrin with achiral compounds, while maintaining the inclusion complexation of it with chiral compounds as well.

A triazole-bridged bis(β-cyclodextrin) was synthesized via a high-yield Click Chemistry reaction between 6-azido-β-cyclodextrin and 6-propynylamino-β-cyclodextrin, and then it was bonded onto ordered silica gel SBA-15 to obtain a novel triazole-bridged bis(β-cyclodextrin)-bonded chiral stationary phase (TBCDP). The structures of the bridged cyclodextrin and TBCDP were characterized by the infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis. The chiral performance of TBCDP was evaluated by using chiral pesticides and drugs as probes including triazoles, flavanones, dansyl amino acids and β-blockers. Some effects of the composition in mobile phase and pH value on the enantioseparations were investigated in different modes. The nine triazoles, eight flavanones, and eight dansyl amino acids were successfully resolved on TBCDP under the reversed phase with the resolutions of hexaconazole, 2′-hydroxyflavanone, and dansyl-DL-tyrosine, which were 2.49, 5.40, and 3.25 within 30 minutes, respectively. The ten β-blockers were also separated under the polar organic mode with the resolution of arotinolol reached 1.71. Some related separation mechanisms were discussed preliminary. Compared with the native cyclodextrin stationary phase (CDSP), TBCDP has higher enantioselectivity to separate more analytes, which benefited from the synergistic inclusion ability of the two adjacent cavities and bridging linker of TBCDP, thereby enabling it a promising prospect in chiral drugs and food analysis.

Mesoporous Fe-Cu@SiO2 core-shell catalyst was synthesized and assessed for its catalytic activity in the ozonation of salicylic acid (SA). The synthesized catalyst was characterized by XRD, TEM, SEM, XPS, H2-TPR, etc. Fe-Cu@SiO2 exhibited a regular spherical shape and had the surface area at 1216 m2 g−1. The wrapping of metal components and their strong interaction prevented metal leaching. Fe-Cu@SiO2 showed the highest activity for SA mineralization when compared with Fe@SiO2 and Cu@SiO2. In Fe-Cu@SiO2/O3, 88% TOC was removed, which was 2.5 times as much as that in sole ozonation. SA degradation efficiency in Fe-Cu@SiO2/O3 increased with initial pH. O3, ·OH and H2O2 were the main reactive oxygen species accounting for SA mineralization. Due to their scavenging effect of ·OH, NH4+, NO3− and humic acids would inhibit the degradation efficiency of Fe-Cu@SiO2/O3. Acidic sites, oxygen vacancies and the Fe-Cu(I/II) electron transfer were responsible for ozone decomposition and ·OH generation. SA mineralization proceeded through the ·OH mechanism. Moreover, SA mineralization in O3 and Fe-Cu@SiO2/O3 both exhibited a two-stage pseudo first-order kinetics (stage I: 0–45 min; stage II: 45–120 min). The degradation intermediates were detected to investigate the reaction pathway. ORP and EEM were used to monitor the degradation process. Great difference was found for carboxylic acids accumulation in O3 and Fe-Cu@SiO2/O3. The accelerated removal of oxalic acid and humic acid-like intermediates were responsible for the two-stage pseudo first-order kinetics.

Quaternary semiconductor film consists of ZnO, ZnSe, CdSe and MoS2 was designed to establish a core-shell structure to achieve the photoelectrochemical oxidation of amoxicillin. The hybrid photoelectrode was fabricated on a FTO substrate from bath deposition methods. The hierarchical ZnSe/CdSe/MoS2 shell was covered uniformly on ZnO nanorod core which provided a direct pathway for electron transfer, large surface area to enhance light absorption and increase active sites. The quaternary photoelectrode exhibited a photocurrent density of 26.86 mA/cm2 at 0 V vs. Ag/AgCl under UV–visible light illumination, which was 31.9 times, 16.7 times and 1.6 times of that of the bare ZnO nanorods, binary ZnO/ZnSe and ternary ZnO/ZnSe/CdSe photoelectrodes, respectively. 10 ppm of amoxicillin was completely degraded in 30 min by the quaternary working electrode with an applied bias of 0.5 V vs. Ag/AgCl. The reusability and stability of quaternary electrode was demonstrated by 3-run recycling experiments. The enhanced photoelectrochemical performance of quaternary photoelectrode can be attributed to the enhancement of light absorption and increased active sites from the coverage of visible-active layers, the accelerated charge separation from the formation of p-n junction and reduced photocorrosion of CdSe from the protection of MoS2 on the surface.

Ternary CdS-MoS2 coated ZnO nanobrush photoelectrode from chemical bath deposition was successfully fabricated on a FTO substrate for photocatalytic degradation of amoxicillin. The vertically grown ZnO core on FTO substrates provided a direct pathway for electron transfer; while the well-crystallized CdS/MoS2 shell offered effective visible light absorption and increased active sites. Prolonged lifetime of charge carriers was demonstrated by transient photovoltage (TPV) measurement. The ternary brush-type electrode exhibited enhanced photoelectrochemical performance with a photocurrent density of 20.32 mA/cm2 at 0 V vs. Ag/AgCl under visible light illumination (λ ≧ 420 nm), which was 5.2 times, 1.8 times and 3.6 times of that of pristine CdS, CdS-MoS2 film and ZnO/CdS nanobrush, respectively. The improved photoelectrochemical activity was ascribed to the enhancement of light absorption, appropriate band alignment and prolonged charge carriers’ lifetime. The ZnO/CdS-MoS2 nanobrush film degraded 94% of amoxicillin in 60 min, exhibiting promising photocatalytic activity under visible light illumination (λ ≧ 420 nm). The reusability and stability of the electrode were evaluated by recycling experiments. The intermediates of amoxicillin oxidation were also identified and the degradation pathway was proposed.

The same amount of metal was deposited on the surface of three-dimensional mesoporous MCM-48 by a facile impregnation-calcination method for catalytic ozonation of pharmaceutical and personal-care products in the liquid phase. At 120 min reaction time, Co/MCM-48 and Ce/MCM-48 showed 46.6 and 63.8% mineralization for clofibric acid (CA) degradation, respectively. Less than 33% mineralization was achieved with Co/MCM-48 and Ce/MCM-48 during sulfamethazine (SMZ) ozonation. In the presence of monometallic oxides modified MCM-48 catalysts, total organic carbon (TOC) removal of diclofenac sodium (DCF) was around 80%. The composite Co-Ce/MCM-48 catalyst exhibited significantly higher activity in terms of TOC removal of CA (83.6%), SMZ (51.7%) and DCF (86.8%). Co-Ce/MCM-48 inhibited efficiently the accumulation of small molecular carboxyl acids during ozonation. A detailed research was conducted to detect the nature of material structure and mechanism of catalytic ozonation by using a series of characterizations. The main reaction pathway of CA was determined by the analysis of liquid chromatography-mass spectrometry, in line with the results of frontier electron density calculations that reactive oxygen species (ROSs) were easy to attack negative regions of pharmaceuticals. The Si-O-Si, Co···HO-Si-O-Si-OH···Ce, and O

Highly dispersed Ag-g-C3N4 hybrid was synthesized successfully by a simple calcination method in present study. The samples were characterized by TEM, XRD, XPS, BET and UV–vis DRS. The results indicate that Ag element are existent as metallic silver and highly dispersed in the matrix of g-C3N4 nanosheet. It was used as active catalyst for photocatalytic ozonation of acetaminophen (ACE) (solar light/Ag-g-C3N4/O3). The results showed that the apparent rate constant of mineralize ACE by solar light/4% Ag-g-C3N4/O3 during 120 min is almost 2 times as large as that with solar light/g-C3N4/O3. The mechanism of photocatalytic ozonation with 4% Ag-g-C3N4 was further confirmed. In this system, Ag acts as not only a good photo-generated electron acceptor for photocatalysis but also a beneficial decomposition center for ozone. Subsequently, holes and hydroxyl radicals both make contribution to the mineralization of ACE in solar light/4% Ag-g-C3N4/O3 process. A superior synergistic effect was observed in mineralization of ACE according to the synergy index of 5.3. Furthermore, Effects of various pH values and silver contents on the ACE mineralization were evaluated. The pathway of ACE degradation in photocatalytic ozonation system with 4% Ag-g-C3N4 was also proposed.

This paper described the use of modified mesoporous molecular sieves to remove clofibric acid through catalytic ozonation. The mesoporous silicate MCM-48 and Cu-substituted MCM-48 (Cu-MCM-48) with different Cu contents were prepared by hydrothermal method in surfactant solutions. The catalyst was characterized by XRD, UV–vis, and XPS, indicating that copper was successfully doped in the framework of three-dimensional MCM-48 and Cu-O-Si linkage was formed in Cu-MCM-48 samples. The SEM and TEM graphs exhibited that the cubic arrays were highly homogeneous and well-ordered. However, high Cu contents destroyed the basic structure of pure MCM-48 and metallic nanometric clusters accumulated on the surface of samples. The degradation and mineralization of clofibric acid (CA) were investigated with the presence of Cu modified MCM-48 (Cu-MCM-48) during ozonation. When the molar ratio of Si/Cu was 60, TOC removal reached 41.1% at 60 min oxidation time. The catalytic mechanism of Cu60-MCM-48 was also investigated by using density functional theory (DFT). The radical quenching experiments revealed that hydroxyl radical ( OH) and superoxide radical ( O2−) were the reactive oxygen species (ROS) for CA degradation. Cu60-MCM-48 showed favorable removal efficiency in the mild acid condition and remained high Lewis acid amount after reactions according to the results of Fourier transformer infrared (FTIR) of adsorbed pyridine. Furthermore, the possible reaction routes including C1 O and C4 Cl bonds destroying and aromatic ring cleavage were proposed by HPLC-MS. 2-hydroxyisobutiric acid was the main intermediate in ozonation process with the presence of Cu60-MCM-48.

A diureido bridged

E-peroxone (EP) was one of the most attractive AOPs for removing refractory organic compounds from water, but the high energy consumption for in situ generating H2O2 and its low reaction efficiency for activating O3 under acidic conditions made the obstacles for its practical application. In this study, cerium oxide was loaded on the surface of graphite felt (GF) by the hydrothermal method to construct the efficient electrode (CeOx/GF) for mineralizing carbamazepine (CBZ) via EP process. CeOx/GF was an efficient cathode, which led to 69.4% TOC removal in CeOx/GF-EP process with current intensity of 10 mA in 60 min. Moreover, CeOx/GF had the flexible application in the pH range from 5.0 to 9.0, TOC removal had no obvious decline with decrease of pH. Comparative characterizations showed that CeOx could enhance surface hydrophilicity and reduce the charge-transfer resistance of GF. About 5.4 mg/L H2O2 generated in CeOx/GF-EP process, which was 2.1 times as that in GF-EP process. The greater ozone utility was also found in CeOx/GF-EP process. More O3 was activated into hydroxyl radicals, which accounted for the mineralization of CBZ. An interfacial electron transfer process was revealed, which involved the function of oxygen vacancies and Ce3+/Ce4+ redox cycle. CeOx/GF had the good recycling property in fifth times’ use.

Herein, we demonstrated the construction of three-dimensional (3D) cerium oxide (CeO

Background Colorectal cancer (CRC) is one of the frequently occurred malignancies in the world. To date, several onco-microRNAs (miRNAs or miRs), including miR-96, have been identified in the pathogenesis of CRC. In the present study, we aimed to corroborate the oncogenic effect of miR-96 on CRC and to identify the specific mechanisms related to AMPKα2/FTO/m6A/MYC. Methods RT-qPCR and Western blot analysis were performed to examine the expression pattern of miR-96, AMPKα2, FTO and MYC in the clinical CRC tissues and cells. The relationship between miR-96 and AMPKα2 was then predicted using in silico analysis and identified by dual-luciferase reporter assay. Gain- or loss-of-function approaches were manipulated to evaluate the modulatory effects of miR-96, AMPKα2, FTO and MYC on cell growth, cycle progression and apoptosis. The mechanism of FTO-mediated m6A modification of MYC was analyzed via Me-RIP and PAR-CLIP analysis. The mediatory effects of miR-96 antagomir on cancerogenesis were validated in vivo. Results miR-96, FTO and MYC were upregulated, while AMPKα2 was downregulated in CRC tissues and cells. miR-96 could down-regulate AMPKα2, which led to increased expression of FTO and subsequent upregulated expression of MYC via blocking its m6A modification. This mechanism was involved in the pro-proliferative and anti-apoptotic roles of miR-96 in CRC cells. Besides, down-regulation of miR-96 exerted inhibitory effect on tumor growth in vivo. Conclusions Taken together, miR-96 antagomir could potentially retard the cancerogenesis in CRC via AMPKα2-dependent inhibition of FTO and blocking FTO-mediated m6A modification of MYC, highlighting novel mechanisms associated with colorectal cancerogenesis.

The low efficiency of peroxone (O

The massive emission of bisphenol A (BPA) has imposed adverse effects on both ecosystems and human health. Herein, nanoporous MoS