Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases:Mechanisms and future perspectives

Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.

6-Phosphogluconate dehydrogenase 2 bridges the OPP and shikimate pathways to enhance aromatic amino acid production in plants

The oxidative pentose phosphate(OPP)pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids(AAAs),which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth.However,genetic evidence linking the two pathways is largely unclear.In this study,we identified 6-phosphogluconate dehydrogenase 2(PGD2),the rate-limiting enzyme of the cytosolic OPP pathway,through suppressor screening of arogenate dehydrogenase 2(adh2)in Arabidopsis.Our data indicated that a single amino acid substitution at position 63(glutamic acid to lysine)of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2,thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2.Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue.Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities,thus exhibiting distinct AAAs producing capability.These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2.The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds.

Efficient removal of phosphate from aqueous solution using novel magnetic nanocomposites with Fe_3O_4@SiO_2 core and mesoporous CeO_2 shell

Fe_3O_4@SiO_2 magnetic nanoparticles functionalized with mesoporous cerium oxide（Fe_3O_4@SiO_2@mCeO_2） was fabricated as a novel adsorbent to remove phosphate from water. The prepared adsorbent was characterized by X-ray diffractometry（XRD）, transmission electron microscopy（TEM）, nitrogen adsorption-desorption and vibrating sample magnetometry（VSM）, and its phosphate removal performance was investigated through the batch adsorption studies. Characterization results confirmed that mesoporous cerium oxide was successfully assembled on the surface of Fe_3O_4@SiO_2 nanoparticles, and the synthesized adsorbent possessed a typical core-shell structure with a BET surface area of 195 m^2/g, accessible mesopores of 2.6 nm, and the saturation magnetization of 21.11 emu/g. The newly developed adsorbent had an excellent performance in adsorbing phosphate, and its maximum adsorption capacity calculated from the Langmuir model was 64.07 mg/g. The adsorption was fast, and the kinetic data could be best fitted with the pseudo-second-order kinetic model. The phosphate removal decreased with the increase of solution pH（2 to 10）, while the higher ionic strength slightly promoted the phosphate adsorption. The presence of Cl~– and SO^（2–）_4 could enhance the adsorption of phosphate whereas HCO~–_ 3 had interfering effect on the phosphate adsorption. The adsorption mechanism was studied by analyzing Zeta potential and FTIR spectroscopy, and the results indicated that the replacement of the surface hydroxyl groups by phosphate ions with the formation of inner-sphere complex played a key role in the phosphate adsorption. The spent adsorbent could be quickly separated from aqueous solution with the assistance of the external magnetic field, and the adsorbed phosphate could be effectively desorbed using a 1 mol/L NaOH solution.

Direct synthesis of α-hydroxyketone phosphates from terminal alkynes and H-phosphine oxides in the presence of PhI(OAc)2 and H2O

A simple and highly efficient one-pot method for the construction of α-hydroxyketone phosphates from terminal alkynes and H-phosphine oxides has been developed in the presence of PhI（OAc）2 and H20. The present protocol provides an attractive approach to α-hydroxyketone phosphates in good to high yields, with the advantages of operation simplicity, the use of commercially available materials, broad substrate scope, high atom efficiency and good tolerance to scale-up synthesis.

Glycolytic Shunts Replenish the Calvin-Benson-Bassham Cycle as Anaplerotic Reactions in Cyanobacteria

The recent discovery of the Entner-Doudoroff(ED)pathway as a third glycolytic route beside Embden-Meyerhof-Parnas(EMP)and oxidative pentose phosphate(OPP)pathway in oxygenic photoautotrophs requires a revision of their central carbohydrate metabolism.In this study,unexpectedly,we observed that deletion of the ED pathway alone,and even more pronounced in combination with other glycolytic routes,diminished photoautotrophic growth in continuous light in the cyanobacterium Synechocystis sp.PCC 6803.Furthermore,we found that the ED pathway is required for optimal glycogen catabolism in parallel to an operating Calvin-Benson-Bassham(CBB)cycle.It is counter-intuitive that glycolytic routes,which are a reverse to the CBB cycle and do not provide any additional biosynthetic intermediates,are important under photoautotrophic conditions.However,observations on the ability to reactivate an arrested CBB cycle revealed that they form glycolytic shunts that tap the cellular carbohydrate reservoir to replenish the cycle.Taken together,our results suggest that the classical view of the CBB cycle as an autocatalytic,completely autonomous cycle that exclusively relies on its own enzymes and C02 fixation to regenerate ribulose-1,5-bisphosphate for Rubisco is an oversimplification.We propose that in common with other known autocatalytic cycles,the CBB cycle likewise relies on anaplerotic reactions to compensate for the depletion of intermediates,particularly in transition states and under fluctuating light conditions that are common in nature.