Metabolomics reveals the importance of metabolites in Mussaenda pubescens for antioxidant properties and quality traits.

Mussaenda pubescens (Mp) is a valuable medicinal plant that has traditionally been used for medicinal purposes or as a tea substitute. However, there are few studies on the comprehensive and dynamic evaluation of Mp metabolites. This study used an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach and biochemical analysis to investigate substance changes in leaves at three different stages and elucidate the relationship between metabolites and antioxidant capacity. The findings showed that Mp leaves contained 957 metabolites, the majority of which were phenolic acids, lipids, and terpenoids. The metabolite profiling of Mp leaves was significantly influenced by their growth and development at different stages. A total of 317 differentially accumulated metabolites (DAMs) were screened, including 150 primary metabolites and 167 secondary metabolites, with 202 DAMs found in bud leaf vs. tender leaf, 54 DAMs in tender leaf vs. mature leaf, and 254 DAMs in bud leaf vs. mature leaf. Total phenolics, flavonoids, and anthocyanin concentrations decreased as Mp leaves grew and developed, whereas terpenoids increased significantly. The secondary metabolites also demonstrated a positive correlation with antioxidant activity. Phenolics, flavonoids, terpenoids, and anthocyanins were the primary factors influencing the antioxidant activity of leaves. These findings provide new insights into the metabolite formation mechanism, as well as the development and utilization of Mp tea.

Strain Engineering for Electrocatalytic Overall Water Splitting.

Strain engineering is a novel method that can achieve superior performance for different applications. The lattice strain can affect the performance of electrochemical catalysts by changing the binding energy between the surface-active sites and intermediates and can be affected by the thickness, surface defects and composition of the materials. In this review, we summarized the basic principle, characterization method, introduction strategy and application direction of lattice strain. The reactions on hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are focused. Finally, the present challenges are summarized, and suggestions for the future development of lattice strain in electrocatalytic overall water splitting are put forward.

Effects of emission control areas on sulfur-oxides concentrations--Evidence from the coastal ports in China.

The setting of Sulfur limitations in Emission Control Areas (ECAs) is a crucial action of marine environmental governance at the international regulatory levels. In this study, the overall and structural impacts of the two rounds of ECA policies on SOx concentrations were quantified using synthetic control method (SCM) based on time-series data from Chinese coastal ports from 2005 to 2020. From the outcomes, the 1st round of ECA policy announced in 2015 intensified the competition between ECA and non-ECA ports and provided strong support for ECA expansion and enhanced regulation in 2019. In addition, the restrictions on the Sulfur content of marine fuels under the 1st round of ECA policy has only effectively reduced the SOx concentration in the Bohai Rim and the Yangtze River Delta region, whereas the impact on the Pearl River Delta region isn't significant. However, the 2nd round of ECA policy has only effectively impacted the Bohai Rim. In general, the effect of the 1st round of ECA policy is better than that of the 2nd round, which is mainly because the favorable effect of the further expansion of ECA policy is offset by a significant increase in vessel activity in Chinese coastal ports.

Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer-binding protein beta.

Dexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 µg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling-induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer-binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c-Jun N-terminal kinase (JNK)/p-38 signaling pathway, inhibiting microglial M1 polarization-mediated inflammation in the central nervous system.

Adenosine Triphosphate-Activated Cascade Reactor for On-Demand Antibacterial Treatment Through Controlled Hydroxyl Radical Generation.

Nanozymes have shown promise for antibacterial applications, but their effectiveness is often hindered by low catalytic performances in physiological conditions and uncontrolled production of hydroxyl radicals (·OH). To address these limitations, a comprehensive approach is presented through the development of an adenosine triphosphate (ATP)-activated cascade reactor (GGPcs). The GGPcs reactor synergistically combines the distinct properties of zeolitic imidazolate framework-8 (ZIF-8) and chitosan-integrated hydrogel microsphere. The ZIF-8 allows for the encapsulation of G-quadruplex/hemin DNAzyme to achieve ATP-responsive ·OH generation at neutral pH, while the hydrogel microsphere creates a confinement environment that facilitates glucose oxidation and provides a sufficient supply of H2 O2 . Importantly, the integrated chitosan in the hydrogel microsphere shields ZIF-8 from undesired disruption caused by gluconic acid, ensuring the responsive specificity of ZIF-8 toward ATP. By activating GGPcs with ATP secreted by bacteria, its effectiveness as an antibacterial agent is demonstrated for the on-demand treatment of bacterial infection with minimal side effects. This comprehensive approach has the potential to facilitate the design of advanced nanozyme systems and broaden their biological applications.

Double-Shelled Porous g-C3 N4 Nanotubes Modified with Amorphous Cu-Doped FeOOH Nanoclusters as 0D/3D Non-Homogeneous Photo-Fenton Catalysts for Effective Removal of Organic Dyes.

Graphite phased carbon nitride (g-C3 N4 ) has attracted extensive attention attributed to its non-toxic nature, remarkable physical-chemical stability, and visible light response properties. Nevertheless, the pristine g-C3 N4 suffers from the rapid photogenerated carrier recombination and unfavorable specific surface area, which greatly limit its catalytic performance. Herein, 0D/3D Cu-FeOOH/TCN composites are constructed as photo-Fenton catalysts by assembling amorphous Cu-FeOOH clusters on 3D double-shelled porous tubular g-C3 N4 (TCN) fabricated through one-step calcination. Combined density functional theory (DFT) calculations, the synergistic effect between Cu and Fe species could facilitate the adsorption and activation of H2 O2 , and the separation and transfer of photogenerated charges effectively. Thus, Cu-FeOOH/TCN composites acquire a high removal efficiency of 97.8%, the mineralization rate of 85.5% and a first-order rate constant k = 0.0507 min-1 for methyl orange (MO) (40 mg L-1 ) in photo-Fenton reaction system, which is nearly 10 times and 21 times higher than those of FeOOH/TCN (k = 0.0047 min-1 ) and TCN (k = 0.0024 min-1 ), respectively, indicating its universal applicability and desirable cyclic stability. Overall, this work furnishes a novel strategy for developing heterogeneous photo-Fenton catalysts based on g-C3 N4 nanotubes for practical wastewater treatment.

Novel Strain Engineering Combined with a Microscopic Pore Synergistic Modulated Strategy for Designing Lattice Tensile-Strained Porous V2C-MXene for High-Performance Overall Water Splitting.

Transition metal carbon/nitride (MXene) holds immense potential as an innovative electrocatalyst for enhancing the overall water splitting properties. Nevertheless, the re-stacking nature induced by van der Waals force remains a significant challenge. In this work, the lattice tensile-strained porous V2C-MXene (named as TS(24)-P(50)-V2C) is successfully constructed via the rapid spray freezing method and the following hydrothermal treatment. Besides, the influence of lattice strain degree and microscopic pores on the catalytic ability is reviewed and explored systematically. The lattice tensile strain within V2C-MXene could widen the interlayer spacing and accelerate the ion transfer. The microscopic pores could change the ion transmission path and shorten the migration distance. As a consequence, the obtained TS(24)-P(50)-V2C shows extraordinary hydrogen evolution reaction and oxygen evolution reaction activity with the overpotential of 154 and 269 mV, respectively, at the current density of 10 mA/cm2, which is quite remarkable compared to the MXene-based electrocatalysts. Moreover, the overall water splitting device assembled using TS(24)-P(50)-V2C as both anode and cathode demonstrates a low cell voltage requirement of 1.57 V to obtain 10 mA/cm2. Overall, the implementation of this work could offer an exciting avenue to overcome the re-stacking issue of V2C-MXene, affording a high-efficiency electrocatalyst with superior catalytic activity and desirable reaction kinetics.

Liquid nitrogen quenching inducing lattice tensile strain to endow nitrogen/fluorine co-doping Fe3O4 nanocubes assembled on porous carbon with optimizing hydrogen evolution reaction.

In this work, the lattice tensile strain of nitrogen/fluorine co-doping ferroferric oxide (Fe3O4) nanocubes assembled on chrysanthemum tea-derived porous carbon is induced through a novel liquid nitrogen quenching treatment (named as TS-NF-FO/PCX-Y, TS: Tensile strain, NF: Nitrogen/Fluorine co-doping, FO: Fe3O4, PC: Porous carbon, X: The weight ratio of KOH/carbon, Y: The adding amount of porous carbon). Besides, the electrocatalytic activity influenced by the adding amount of porous carbon, the type of dopant, and the introduction of lattice tensile strain is systematically studied and explored. The interconnected porous carbon could improve electrical conductivity and prevent Fe3O4 nanocubes from aggregating. The induced nitrogen/fluorine could cause extrinsic defects and tailor the intrinsic electron state of the host materials. Lattice tensile strain could tailor the surface electronic structure of Fe3O4 via changing the dispersion of surface atoms and their bond lengths. Impressively, the designed TS-NF-FO/PC5-0.25 delivers a low overpotential of 207.3 ± 0.4 mV at 10 mA/cm2 and demonstrates desirable reaction dynamics. Density functional theory calculations illustrate that the electron structure and hydrogen adsorption free energy (ΔG*H) are optimized by the synergistic effect among porous carbon, nitrogen/fluorine co-doping and lattice tensile strain, thus promoting hydrogen evolution reaction (HER) catalytic activity. Overall, this work paves the way to unravel the enhancement mechanism of HER on transition metal oxide-based materials by electronic structure and phase composition modulation strategy.

Spatiotemporal variations of NO2 and its driving factors in the coastal ports of China.

Nitrogen Dioxide (NO2) is one of the major air pollutants in coastal ports of China. Understanding the spatiotemporal varying effects of driving factors of NO2 is vital for the implementation of differentiated air pollution control measures for different port areas. Based on the Ozone Monitoring Instrument (OMI) satellite data, we adopted a Geographically and Temporally Weighted Regression (GTWR) model to explore the influences of meteorological and socioeconomic factors on the NO2 Vertical Column Concentrations (VCDs) in coastal ports of China from 2015 to 2021. The results indicate that NO2 VCD in most ports has decreased since 2016 and the ports with serious NO2 pollution are mainly distributed in northern China. The associations between NO2 VCD levels and their drivers exhibit obvious spatiotemporal heterogeneity. Higher wind speed and relative humidity are more helpful to alleviate NO2 pollution in ports of the Bohai Rim and the Pearl River Delta. Cargo throughput has more closely associated with NO2 pollution in Beibu Gulf in recent years, yet there is no significant association found for Shanghai ports. The positive relationship between transportation emissions and NO2 VCD is more significant in southern ports. This work provides some implications for the formulation of targeted emission reduction policies for different ports along the Chinese coast.

Co-Dissolved Isostructural Polyoxovanadates to Construct Single-Atom-Site Catalysts for Efficient CO2 Photoreduction.

We explored a co-dissolved strategy to embed mono-dispersed Pt center into V2 O5 support via dissolving [PtV9 O28 ]7- into [V10 O28 ]6- aqueous solution. The uniform dispersion of [PtV9 O28 ]7- in [V10 O28 ]6- solution allows [PtV9 O28 ]7- to be surrounded by [V10 O28 ]6- clusters via a freeze-drying process. The V centers in both [PtV9 O28 ]7- and [V10 O28 ]6- were converted into V2 O5 via a calcination process to stabilize Pt center. These double separations can effectively prevent the Pt center agglomeration during the high-temperature conversion process, and achieve 100 % utilization of Pt in [PtV9 O28 ]7- . The resulting Pt-V2 O5 single-atom-site catalysts exhibit a CH4 yield of 247.6 µmol g-1 h-1 , 25 times higher than that of Pt nanoparticle on the V2 O5 support, which was accompanied by the lactic acid photooxidation to form pyruvic acid. Systematical investigations on this unambiguous structure demonstrate an important role of Pt-O atomic pair synergy for highly efficient CO2 photoreduction.

Oxidation of N-Alkyl(iso)quinolinium Salts Over TEMPO@Metal-Organic Framework Heterogeneous Photocatalyst†.

Quinolones and isoquinolones are of particular importance to pharmaceutical industry due to their diverse biological activities. However, their synthetic protocols were limited by high toxicity, high energy consumption, poor functional group tolerance and noble metal catalyst. This study concerns the development of a series of TEMPO@PCN-222 (TEMPO: 2,2,6,6-tetramethylpiperidinyl-1-oxy; PCN: porous coordination network) composite photocatalysts by coordinating different amount of 4-carboxy-TEMPO with the secondary building units of PCN-222. Upon visible-light irradiation, photogenerated holes in the highest occupied molecular orbital of PCN-222 can smoothly transfer to TEMPO, which can significantly boost the photosynthesis of bioactive (iso)quinolones from readily available N-alkyl(iso)quinolinium salts. TEMPO@PCN-222 exhibits an outstanding catalytic stability and substrate tolerance with a 1-methyl-2-quinolinone yield of 86.7 %, over four times that with PCN-222 (21.4 %). This work provides a new route to construct composite photocatalysts from abundant starting materials for efficient photosynthesis of high value-added chemicals.

HemI 2.0: an online service for heatmap illustration.

Recent high-throughput omics techniques have produced a large amount of biological data. Visualization of big omics data is essential to answer a wide range of biological problems. As a concise but comprehensive strategy, a heatmap can analyze and visualize high-dimensional and heterogeneous biomolecular expression data in an attractive artwork. In 2014, we developed a stand-alone software package, Heat map Illustrator (HemI 1.0), which implemented three clustering methods and seven distance metrics for heatmap illustration. Here, we significantly improved 1.0 and released the online service of HemI 2.0, in which 7 clustering methods and 22 types of distance metrics were implemented. In HemI 2.0, the clustering results and publication-quality heatmaps can be exported directly. For an in-depth analysis of the data, we further added an option of enrichment analysis for 12 model organisms, with 15 types of functional annotations. The enrichment results can be visualized in five idioms, including bubble chart, bar graph, coxcomb chart, pie chart and word cloud. We anticipate that HemI 2.0 can be a helpful web server for visualization of biomolecular expression data, as well as the additional enrichment analysis. HemI 2.0 is freely available for all users at: https://hemi.biocuckoo.org/.

Bottom aquaculture can improve the basic trophic pathways and enhance the secondary production: Implications from benthic food web analysis.

To evaluate the impact of bottom aquaculture on benthic ecosystems, characteristics of benthic food web were studied using stable isotope techniques during four seasons in a Manila clam (Ruditapes philippinarum) bottom aquaculture area in a semi-enclosed bay, China. Results showed that although nitrogen stable isotope values of food sources (particulate organic matter and phytoplankton) had significant seasonal differences, there were no significant seasonal changes for benthic food web structure. Manila clam bottom aquaculture can enhance the secondary productivity and improve the basic trophic pathways by providing bio-deposits. Besides particulate organic matter and phytoplankton, Manila clam could feed on self-generated feces with high nitrogen stable isotope values, and benthic micro- and macroalga with high carbon stable isotope values. Secondary productivity of the stations with a high degree of aquaculture was higher than that of stations with a low degree. Bivalve bottom culture may have a positive impact on benthic ecosystem functioning.

PRDX3 promotes resistance to cisplatin in gastric cancer cells.

Objective: This study aims to investigate peroxiredoxin 3 (PRDX3) expression in gastric cancer tissue and its effects on cisplatin resistance in gastric cancer cells and its possible mechanism. Methods: PRDX3 expression in human gastric cancer tissue microarrays was detected via immunohistochemistry. The PRDX3 small interfering RNA (siPRDX3 group) and the negative control siNC (siNC group) were transfected into AGS and MKN-74 cell lines, respectively, whereas a blank control group was set up. Each group was treated with different cisplatin concentrations (0, 5, 10, 15, 20, 25, and 30 µg/ml), and the half-inhibitory concentration (IC50) of each group of the two cell lines was calculated using the CCK8 assay. The corresponding IC50 concentration of the siPRDX3 group in the two cell lines was used to treat cells of each group. Flow cytometry was used to detect cell apoptosis, and Western blotting was used to detect the expression levels of cleaved caspase-3 and Bax in each group. Results: PRDX3 was overexpressed in gastric adenocarcinoma tissue compared with adjacent noncancer tissue (P = 0.0053). After cisplatin treatment, the IC50 in the siPRDX3 group of AGS cells (5.91 ± 0.18 µg/ml) and the siPRDX3 group of MKN-74 cells (3.48 ± 0.30 µg/ml) was significantly lower than in the corresponding siNC groups (10.01 ± 0.99 and 6.39 ± 0.70 µg/ml; P = 0.0022 and 0.0027, respectively). AGS cells (38.81% ± 1.69%) and MKN-74 cells (25.03% ± 2.80%) in the siPRDX3 group showed significantly higher apoptosis rates than in the corresponding siNC groups (23.17% ± 1.43% and 16.7% ± 1.39%; P = 0.0003 and 0.0099, respectively). The expression levels of cleaved caspase-3 and Bax were significantly higher in the siPRDX3 group of both cell lines than in the siNC group (P < 0.0001). Conclusion: PRDX3 increases the gastric cancer cell resistance to cisplatin by reducing apoptosis and thus may serve as a target to overcome cisplatin resistance.

Feeding Carbonylation with CO2 via the Synergy of Single-Site/Nanocluster Catalysts in a Photosensitizing MOF.

Solar-driven carbonylation with CO2 replacing toxic CO as a C1 source is of considerable interest; however it remains a great challenge due to the inert CO2 molecule. Herein, we integrate cobalt single-site and ultrafine CuPd nanocluster catalysts into a porphyrin-based metal-organic framework to construct composite photocatalysts (Cu1Pd2)z@PCN-222(Co) (z = 1.3, 2.0, and 3.0 nm). Upon visible light irradiation, excited porphyrin can concurrently transfer electrons to Co single sites and CuPd nanoclusters, providing the possibility for coupling CO2 photoreduction and Suzuki/Sonogashira reactions. This multicomponent synergy in (Cu1Pd2)1.3@PCN-222(Co) can not only replace dangerous CO gas but also dramatically promote the photosynthesis of benzophenone in CO2 with over 90% yield and 97% selectivity under mild condition. Systematic investigations clearly decipher the function and collaboration among different components in these composite catalysts, highlighting a new insight into developing a sustainable protocol for carbonylation reactions by employing greenhouse gas CO2 as a C1 source.

Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19.

Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion: The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.

Aggregation Induced Emission and Nonlinear Optical Properties of an Intramolecular Charge-Transfer Compound.

Intramolecular charge transfer (ICT) compounds have attracted wide attention for their potential applications in optoelectronic materials and devices such as fluorescent sensors, dye-sensitized solar cells, organic light emitting diodes and nonlinear optics. In this work, we have synthesized a new ICT compound, dimethyl-[4-(7-nitro-benzo[1,2,5]thiadiazol-4-yl)-phenyl]-amine (BTN), and have fabricated it into low dimensional micro/nano structures with well-defined morphologies. These self-assembled nanostructures exhibit high efficiency solid state fluorescence via an aggregation induced emission mechanism, which overcomes the defect of fluorescence quenching caused by aggregation in the solid state of traditional luminescent materials. We also explored and studied the nonlinear optical properties of this material through the Z-scan method, and found that this material exhibits large third-order nonlinear absorption and refraction coefficients, which promises applications of the materials in the fields of nonlinear optics and optoelectronics.

Atg9-centered multi-omics integration reveals new autophagy regulators in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, Atg9 is an important autophagy-related (Atg) protein, and interacts with hundreds of other proteins. How many Atg9-interacting proteins are involved in macroautophagy/autophagy is unclear. Here, we conducted a multi-omic profiling of Atg9-dependent molecular landscapes during nitrogen starvation-induced autophagy, and identified 290 and 256 genes to be markedly regulated by ATG9 in transcriptional and translational levels, respectively. Unexpectedly, we found most of known Atg proteins and autophagy regulators that interact with Atg9 were not significantly changed in the mRNA or protein level during autophagy. Based on a hypothesis that proteins with similar molecular characteristics might have similar functions, we developed a new method named inference of functional interacting partners (iFIP) to integrate the transcriptomic, proteomic and interactomic data, and predicted 42 Atg9-interacting proteins to be potentially involved in autophagy, including 15 known Atg proteins or autophagy regulators. We validated 2 Atg9-interacting partners, Glo3 and Scs7, to be functional in both bulk and selective autophagy. The mRNA and protein expressions but not subcellular localizations of Glo3 and Scs7 were affected with or without ATG9 during autophagy, whereas the colocalizations of the 2 proteins and Atg9 were markedly enhanced at early stages of the autophagic process. Further analyses demonstrated that Glo3 but not Scs7 regulates the retrograde transport of Atg9 during autophagy. A working model was illustrated to highlight the importance of the Atg9 interactome. Taken together, our study not only provided a powerful method for analyzing the multi-omics data, but also revealed 2 new players that regulate autophagy.Abbreviations: ALP: alkaline phosphatase; Arf1: ADP-ribosylation factor 1; Atg: autophagy-related; Co-IP: co-immunoprecipitation; Cvt: cytoplasm-to-vacuole targeting; DEM: differentially expressed mRNA; DEP: differentially expressed protein; DIC: differential interference contrast; E-ratio: enrichment ratio; ER: endoplasmic reticulum; ES: enrichment score; FC: fold change; FPKM: fragments per kilobase of exon per million fragments mapped; GAP: GTPase-activating protein; GFP: green fluorescent protein; GO: gene ontology; GSEA: gene set enrichment analysis; GST: glutathione S-transferase; HA: hemagglutinin; iFIP: inference of functional interacting partners; KO: knockout; LR: logistic regression; OE: over-expression; PAS: phagophore assembly site; PPI: protein-protein interaction; RFP: red fluorescence protein; RNA-seq: RNA sequencing; RT-PCR: real-time polymerase chain reaction; SCC: Spearman's correlation coefficient; SD-N: synthetic minimal medium lacking nitrogen; THANATOS: The Autophagy, Necrosis, ApopTosis OrchestratorS; Vsn: variance stabilization normalization; WT: wild-type.

METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5.

N6-methyladenosine (m6A) has emerged as the most prevalent post-transcriptional modification on mRNA that contributes prominently to tumorigenesis. However, the specific function of m6A methyltransferase methyltransferase-like 3 (METTL3) in colorectal cancer (CRC) remains elusive. Herein, we explored the biological function of METTL3 in CRC progression. Clinically, METTL3 was frequently upregulated in CRC tissues, cell lines, and plasma samples and its high expression predicted poor prognosis of CRC patients. Functionally, knockdown of METTL3 significantly repressed CRC cell proliferation and migration in vitro, while its overexpression accelerated CRC tumor formation and metastasis both in vitro and in vivo. Mechanistically, METTL3 epigenetically repressed YPEL5 in an m6A-YTHDF2-dependent manner by targeting the m6A site in the coding sequence region of the YPEL5 transcript. Moreover, overexpression of YPEL5 significantly reduced CCNB1 and PCNA expression. Collectively, we identified the pivotal role of METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing YPEL5 expression in an m6A-YTHDF2-dependent manner, suggesting a promising strategy for the diagnosis and therapy of CRC.

Chain conformation of an acidic polysaccharide from green tea and related mechanism of α-amylase inhibitory activity.

An acidic tea polysaccharide (TPSA) isolated from green tea was fractionated using a precipitation-fractionation method into seven fractions with different molecular weights. TPSA was characterized as a hyperbranched polysaccharide with a globular homogeneous conformation by analysis of solution parameters of each fraction using static light scattering and viscosity analyses. Observation by transmission electron microscopy confirmed that TPSA occurred as globular homogeneous particles with size in the range of 20-40 nm. To simulate the branched chain segments of TPSA, four model molecules were designed based on chemical structure of TPSA. Molecular docking analysis indicated that the branched chain segments of TPSA similar to the TPSA-4 model molecule showed preferential binding to α-amylase to form the TPSA/α-amylase complex through hydrogen bonding interactions. Circular dichroism spectroscopy showed that the structure of α-amylase was not significantly affected by TPSA. The mechanism of α-amylase inhibitory activity of TPSA was simulated by molecular docking analysis. The branched chain segments of TPSA similar to the TPSA-4 model molecule likely act as a potential competitor to the starch substrate to inhibit the activity of α-amylase.