Association patterns of ketone bodies with the risk of adverse outcomes according to diabetes status.

AIM: To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all-cause mortality according to diabetes status. METHODS: This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including ß-hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. RESULTS: During a mean follow-up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17-1.49], per 10-fold increase in total KB) and prediabetes (1.35 [1.04-1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09-1.33]). Elevated KB levels were associated with an increased risk of all-cause mortality across the glycaemic spectrum (1.32 [1.23-1.42] for normoglycaemia, 1.45 [1.24-1.71] for prediabetes and 1.47 [1.11-1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P = .009), with 4.9% of deaths attributed to the interactive effects. CONCLUSIONS: Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality.

Intermittent Fasting Improves Social Interaction and Decreases Inflammatory Markers in Cortex and Hippocampus.

Autism spectrum disorder (ASD) is a psychiatric condition characterized by reduced social interaction, anxiety, and stereotypic behaviors related to neuroinflammation and microglia activation. We demonstrated that maternal exposure to Western diet (cafeteria diet or CAF) induced microglia activation, systemic proinflammatory profile, and ASD-like behavior in the offspring. Here, we aimed to identify the effect of alternate day fasting (ADF) as a non-pharmacologic strategy to modulate neuroinflammation and ASD-like behavior in the offspring prenatally exposed to CAF diet. We found that ADF increased plasma beta-hydroxybutyrate (BHB) levels in the offspring exposed to control and CAF diets but not in the cortex (Cx) and hippocampus (Hpp). We observed that ADF increased the CD45 + cells in Cx of both groups; In control individuals, ADF promoted accumulation of CD206 + microglia cells in choroid plexus (CP) and increased in CD45 + macrophages cells and lymphocytes in the Cx. Gestational exposure to CAF diet promoted defective sociability in the offspring; ADF improved social interaction and increased microglia CD206 + in the Hpp and microglia complexity in the dentate gyrus. Additionally, ADF led to attenuation of the ER stress markers (Bip/ATF6/p-JNK) in the Cx and Hpp. Finally, biological modeling showed that fasting promotes higher microglia complexity in Cx, which is related to improvement in social interaction, whereas in dentate gyrus sociability is correlated with less microglia complexity. These data suggest a contribution of intermittent fasting as a physiological stimulus capable of modulating microglia phenotype and complexity in the brain, and social interaction in male mice.

Dynamic Adhesive Behavior and Biofilm Formation of Staphylococcus aureus on Polylactic Acid Surfaces in Diabetic Environments.

Interest in biodegradable implants has focused attention on the resorbable polymer polylactic acid. However, the risk of these materials promoting infection, especially in patients with existing pathologies, needs to be monitored. The enrichment of a bacterial adhesion medium with compounds that are associated with human pathologies can help in understanding how these components affect the development of infectious processes. Specifically, this work evaluates the influence of glucose and ketone bodies (in a diabetic context) on the adhesion dynamics of S. aureus to the biomaterial polylactic acid, employing different approaches and discussing the results based on the physical properties of the bacterial surface and its metabolic activity. The combination of ketoacidosis and hyperglycemia (GK2) appears to be the worst scenario: this system promotes a state of continuous bacterial colonization over time, suppressing the stationary phase of adhesion and strengthening the attachment of bacteria to the surface. In addition, these supplements cause a significant increase in the metabolic activity of the bacteria. Compared to non-enriched media, biofilm formation doubles under ketoacidosis conditions, while in the planktonic state, it is glucose that triggers metabolic activity, which is practically suppressed when only ketone components are present. Both information must be complementary to understand what can happen in a real system, where planktonic bacteria are the ones that initially colonize a surface, and, subsequently, these attached bacteria end up forming a biofilm. This information highlights the need for good monitoring of diabetic patients, especially if they use an implanted device made of PLA.

ß-Hydroxybutyrate and melatonin suppress maladaptive UPR, excessive autophagy and pyroptosis in Aß 1-42 and LPS-Induced SH-SY5Y cells.

BACKGROUND: Alzheimer's disease is a neurological disease characterized by the build-up of amyloid beta peptide (Aß) and lipopolysaccharide (LPS), which causes synapse dysfunction, cell death, and neuro-inflammation. A maladaptive unfolded protein response (UPR), excessive autophagy, and pyroptosis aggravate the disease. Melatonin (MEL) and hydroxybutyrate (BHB) have both shown promise in terms of decreasing Aß pathology. The goal of this study was to see how BHB and MEL affected the UPR, autophagy, and pyroptosis pathways in Aß1-42 and LPS-induced SH-SY5Y cells. MATERIALS AND METHODS: Human neuroblastoma SH-SY5Y cells were treated with BHB, MEL, or a combination of the two after being exposed to A ß1-42 and LPS. Cell viability was determined using the MTT test, and gene expression levels of UPR (ATF6, PERK, and CHOP), autophagy (Beclin-1, LC3II, P62, and Atg5), and pyroptosis-related markers (NLRP3, TXNIP, IL-1ß, and NFκB1) were determined using quantitative Real-Time PCR (qRT-PCR). For statistical analysis, one-way ANOVA was employed, followed by Tukey's post hoc test. RESULTS: BHB and MEL significantly increased SH-SY5Y cell viability in the presence of A ß1-42 and LPS. Both compounds inhibited the expression of maladaptive UPR and autophagy-related genes, as well as inflammatory and pyroptotic markers caused by Aß1-42 and LPS-induced SH-SY5Y cells. CONCLUSION: BHB and MEL rescue neurons in A ß1-42 and LPS-induced SH-SY5Y cells by reducing maladaptive UPR, excessive autophagy, and pyroptosis. More research is needed to fully comprehend the processes behind their beneficial effects and to discover their practical applications in the treatment of neurodegenerative disorders.

Long-term use of investigational ß-Hydroxybutyrate salts in children with multiple acyl-CoA dehydrogenase or pyruvate dehydrogenase deficiency.

Several disorders of energy metabolism have been treated with exogenous ketone bodies. The benefit of this treatment is best documented in multiple acyl-CoA dehydrogenase deficiency (MADD) (MIM#231680). One might also expect ketone bodies to help in other disorders with impaired ketogenesis or in conditions that profit from a ketogenic diet. Here, we report the use of a novel preparation of dextro-ß-hydroxybutyrate (D-ßHB) salts in two cases of MADD and one case of pyruvate dehydrogenase (PDH) deficiency (MIM#312170). The two patients with MADD had previously been on a racemic mixture of D- and L­sodium hydroxybutyrate. Patient #1 found D-ßHB more palatable, and the change in formulation corrected hypernatraemia in patient #2. The patient with PDH deficiency was on a ketogenic diet but had not previously been given hydroxybutyrate. In this case, the addition of D-ßHB improved ketosis. We conclude that NHS101 is a good candidate for further clinical studies in this group of diseases of inborn errors of metabolism.

Empagliflozin alters lipid metabolism in the myocardium and liver in a prediabetes model with severe dyslipidemia.

Background and aims: Recent studies suggest that empagliflozin reduces total and cardiovascular mortality in both diabetic and nondiabetic subjects. Although the exact mechanism is unclear, it is understood to positively affect myocardial energetics, including the metabolism of ketone bodies, lipids, and fatty acids. In this study, we compared empagliflozin effects on lipid metabolism in the heart and liver in a prediabetic rat model with severe dyslipidemia. Materials and methods: Wistar rats served as the control group, while hereditary hypertriglyceridemic (HHTg) rats were used as a nonobese, prediabetic model. Rats were treated with or without empagliflozin at a dose of 10 mg/kg body weight (BW) for 8 weeks. Results: In HHTg rats, empagliflozin decreased body weight and adiposity, improved glucose tolerance, and decreased serum triacylglycerols (TAGs) (p < 0.001). Empagliflozin decreased the activity and gene expression of the lipogenic enzyme SCD-1 (p < 0.001) in the myocardium, which may have led to a decrease in the ectopic accumulation of TAGs and lipotoxic diacylglycerols and lysophosphatidylcholines (p < 0.001). Changes in the myocardial phosphatidylcholine/phosphatidylethanolamine ratio (p < 0.01) and in the fatty acid profile of myocardial phospholipids may have contributed to the antifibrotic effects of empagliflozin. The anti-inflammatory effects of empagliflozin were evidenced by an increased IL-10/TNFα ratio (p < 0.001), a marked decrease in arachidonic acid metabolites (20-HETE, p < 0.001), and an increase in PUFA metabolites (14,15-EETs, p < 0.001) in the myocardium. However, empagliflozin did not significantly affect either the concentration or utilization of ketone bodies. In the liver, empagliflozin decreased lipogenesis and the accumulation of TAGs and lipotoxic intermediates. Its effect on arachidonic acid metabolites and alterations in n-3 PUFA metabolism was less pronounced than in the myocardium. Conclusion: Our findings suggest that empagliflozin treatment in the heart and liver reduced the accumulation of neutral lipids and lipotoxic intermediates and altered the metabolism of n-3 PUFA. In the heart, empagliflozin altered arachidonic acid metabolism, which is likely associated with the anti-inflammatory and antifibrotic effects of the drug. We assume that these alterations in lipid metabolism contribute to the cardioprotective effects of empagliflozin in prediabetic states with severe dyslipidemia.

De- and Rearomatisation of Pyridine in Silylene Chemistry.

Traditional methods relying on metal-ligand cooperation for activating pyridine bonds in de- and rearomatisation are being challenged by the abundant metal-free element species as alternatives. Here, we investigate the de/re-aromatisation of pyridine facilitated by pyridylamino-functionalised silylene reactions with ketones and ketene. The reactivity outcome is highly dependent on the substituents on the ketones. By carefully tuning the steric demand of the ketone, each intermediate of the reaction sequence could be isolated. At room temperature, benzophenone and acetophenone substrates led to dearomatisation of the pyridine moiety, with the case of acetophenone showing an intermediate silaoxirane preceding dearomatisation. However, when subjected to acetone or diphenylketene, only silaoxiranes were formed without dearomatisation of the pyridine moiety. Notably, only benzophenone-derived dearomatised species demonstrate rearomatisation upon heating. Furthermore, the reduced steric bulk of the ketene facilitated further ring expansion with another equivalent of the substrate, forming sila-1,3-dioxolanes. Both steric hindrance and aromatic groups collectively influence the dearomatisation of pyridine in pyridylaminosilylene reactions.

Carbonic Anhydrase Variants Catalyze the Reduction of Dialkyl Ketones with High Enantioselectivity.

Human carbonic anhydrase II (hCAII) naturally catalyzes the reaction between two achiral molecules - water and carbon dioxide - to yield the achiral product carbonic acid through a zinc hydroxide intermediate. We have previously shown that a zinc hydride, instead of a hydroxide, can be generated in this enzyme to create a catalyst for the reduction of aryl ketones. Dialkyl ketones are more challenging to reduce, and the enantioselective reduction of dialkyl ketones with two alkyl groups that are similar in size and electronic properties, is a particularly challenging transformation to achieve with high activity and selectivity. Here, we show that hCAII, as well as a double variant of it, catalyzes the enantioselective reduction of dialkyl ketones with high yields and enantioselectivities, even when the two alkyl groups are similar in size. We also show that variants of hCAII catalyze the site-selective reduction of one ketone over the other in an unsymmetrical aliphatic diketone. Computational docking of a dialkyl ketone to the double variant containing the zinc hydride provides insights into the origins of the reactivity of various substrates and the high enantioselectivity of the transformations and show how a confined environment can control the enantioselectivity of an abiological intermediate.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Ketone body metabolism and the NLRP3 inflammasome in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid-ß (Aß) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aß and tau pathology, with evidence suggesting the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase-1 activation and secretion of IL-1ß and IL-18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and ß-hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.

Effects of angiotensin receptor-neprilysin inhibitor on ketone body metabolism in pre-heart failure/heart failure patients.

Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] µmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients.

Application of 3D­printed porous titanium interbody fusion cage vs. polyether ether ketone interbody fusion cage in anterior cervical discectomy and fusion: A systematic review and meta­analysis update.

The present study aimed to compare the differences between 3D-printed porous titanium and polyether ether ketone (PEEK) interbody fusion cages for anterior cervical discectomy and fusion (ACDF). Literature on the application of 3D-printed porous titanium and PEEK interbody fusion cages for ACDF was searched in the PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang and VIP databases. A total of 1,181 articles were retrieved and 12 were finally included. The Cochrane bias risk assessment criteria and Newcastle-Ottawa scale were used for quality evaluation and Review Manager 5.4 was used for data analysis. The 3D cage group was superior to the PEEK cage group in terms of operative time [mean difference (MD): -7.68; 95% confidence interval (CI): -11.08, -4.29; P<0.00001], intraoperative blood loss (MD: -6.17; 95%CI: -10.56, -1.78; P=0.006), hospitalization time (MD: -0.57; 95%CI: -0.86, -0.28: P=0.0001), postoperative complications [odds ratio (OR): 0.35; 95%CI: 0.15, 0.80; P=0.01], C2-7 Cobb angle (MD: 2.85; 95%CI: 1.45, 4.24; P<0.0001), intervertebral space height (MD: 1.20; 95%CI: 0.54, 1.87; P=0.0004), Japanese Orthopaedic Association Assessment of Treatment (MD: 0.69; 95%CI: 0.24, 1.15; P=0.003) and visual analogue scale score (MD: -0.43; 95%CI: -0.78, -0.07; P=0.02). The difference was statistically significant, while there was no significant difference between the two groups in terms of fusion rate (OR: 1.74; 95%CI: 0.71, 4.27; P=0.23). The use of 3D-printed porous titanium interbody fusion cage in ACDF has the advantages of short operation time, less bleeding loss, shorter hospitalization time and fewer postoperative complications. It can better maintain the cervical curvature and intervertebral height, relieve pain and accelerate postoperative functional recovery.

Differences in Volatile Organic Compounds Between Concussed and Non-concussed Division I Athletes.

Introduction Diagnosing a concussion is challenging because of complex and variable symptoms. Establishing a viable biomarker of injury may rely on physiologic measurements rather than symptomology. Volatile organic compounds (VOCs) such as breath acetone have been identified as potential physiological markers that can capture changes in the utilization of energy substrates post-concussion. Here, we aimed to explore whether differences in VOCs exist between concussed and non-concussed athletes at the initial and later stages of injury recovery. Methods Six (N=6) non-concussed athletes were enrolled as control participants prior to the competitive season. Control participants' breath acetone, heart rate, and anthropometric measures were obtained at rest and throughout a single exercise challenge by breathalyzer. Six (N=6) athletes diagnosed with concussion during the competitive season had breath acetone measured daily until cleared to return to activity or approximately four weeks following enrollment where they participated in an exit exercise challenge having breath acetone, heart rate, and anthropometric measures obtained. Comparisons were made between at-rest measures of concussed and non-concussed participants at multiple time points during the recovery period. Paired t-test comparisons with individuals serving as their own control were used to determine individual differences in recovery. Visual graphs were used to demonstrate differences in obtained measures amongst individuals and between groups during the exercise challenges. Results Results demonstrated statistically significant differences in breath acetone between concussed and control participants when the highest day measured during the first week of concussion was compared to the control participant's resting values (P=0.017). Additionally, when the concussed participants served as their own control and their highest measured day of the first week post-concussion was compared to values when cleared to return to activity or at 26 days post-concussion, there was a significant difference in breath acetone (P=0.028). Comparing breath acetone during exercise between non-concussed and cleared concussed participants or four weeks post-injury, demonstrated no significant differences throughout the challenge or at rest prior. Visual graph comparisons in a single participant before and after concussion suggest differences may appear following exercise during the recovery period. Discussion These results suggest VOCs, particularly breath acetone, have the potential to serve as diagnostic markers of concussion. However, longitudinal research within larger cohorts and with equipment able to expel VOCs other than acetone from measures are needed to make informed recommendations.

Selective Oxidative Cleavage of Benzyl C-N Bond under Metal-Free Electrochemical Conditions.

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation-reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C-N bond. This method selectively oxidatively cleaves the C-N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

Relationships Between Changes in Serum Ketone Body Levels and Metabolic Effects in Patients with Severe Obesity Who Underwent Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Serum ketone bodies increase due to dynamic changes in the lipid metabolisms of patients undergoing bariatric surgery. However, there have been few studies on the role of ketone bodies after bariatric surgery. We aimed to clarify the role of and relationship between the changes in serum ketone bodies and weight loss, as well as between those changes and the metabolic effects after laparoscopic sleeve gastrectomy (LSG). METHODS: We recruited 52 patients with severe obesity who underwent LSG. We measured acetoacetic acid (AcAc) and ß-hydroxybutyric acid (ß-OHB) at the baseline, 1 month, and 6 months after LSG. Subsequently, we compared the changes in the serum ketone bodies with weight-loss effects and various metabolic parameters. RESULTS: At 1 month after LSG, ß-OHB significantly increased (p = 0.009), then significantly decreased 6 months after LSG (p = 0.002). In addition, ß-OHB in patients without Type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH) was notably higher than in patients with T2D at 1 month after LSG (p < 0.001). In the early phase, both AcAc and ß-OHB mainly had strong positive correlations with changes in T2D- and MASH-related parameters. In the middle term after LSG, changes in both AcAc and ß-OHB were positively correlated with changes in lipid parameters and chronic kidney disease-related parameters. CONCLUSION: We demonstrated that the postoperative surge of ketone bodies plays a crucial function in controlling metabolic effects after LSG. These findings suggest the cause- and consequence-related roles of ketone bodies in the metabolic benefits of bariatric surgery.

Determination of the safety of Halomonas sp. KM-1-derived D-ß-hydroxybutyric acid and its fermentation-derived impurities in mice and Japanese adults.

The use of halophilic bacteria in industrial chemical and food production has received great interest because of the unique properties of these bacteria; however, their safety remains under investigation. Halomonas sp. KM-1 intracellularly stores poly-D-ß-hydroxybutyric acid under aerobic conditions and successively secretes D-ß-hydroxybutyric acid (D-BHB) under microaerobic conditions. Therefore, we tested the safety of Halomonas sp. KM-1-derived D-BHB and the impurities generated during D-BHB manufacturing at a 100-fold increased concentration in acute tests using mice and daily intake of 16.0 g D-BHB in Japanese adults for 12 weeks. In the mice test, there were no abnormalities in the body weights or health of mice fed the purified D-BHB or its impurities. In the Japanese adult test, blood parameters and body condition showed no medically problematic fluctuations. These findings indicate that Halomonas sp. KM-1 is safe and can be used for commercial production of D-BHB and its derivatives.

High-Performance Monovalent Selective Cation Exchange Membranes with Ionically Cross-Linkable Side Chains: Effect of the Acidic Groups.

Inspired by the charge-governed protein channels located in the cell membrane, a series of polyether ether ketone-based polymers with side chains containing ionically cross-linkable quaternary ammonium groups and acidic groups have been designed and synthesized to prepare monovalent cation-selective membranes (MCEMs). Three acidic groups (sulfonic acid, carboxylic acid, and phenolic hydroxyl) with different acid dissociation constant (pKa) were selected to form the ionic cross-linking structure with quaternary ammonium groups in the membranes. The ionic cross-linking induced the nanophase separation and constructed ionic channels, which resulted in excellent mechanical performance and high cation fluxes. Interesting, the cation flux of membranes increased as the ionization of acidic groups increase, but the selectivity of MCEMs did not follow the same trend, which was mainly dependent on the affinity between the functional groups and the cations. Carboxyl group-containing MCEMs exhibited the best selectivity (9.01 for Li+/Mg2+), which was higher than that of the commercial monovalent cation-selective CIMS membrane. Therefore, it is possible to prepare stable MCEMs through a simple process using ionically cross-linkable polymers, and tuning acidic groups in the membranes provided an attractive approach to improving the cation flux and selectivity of MCEMs.

Highly sulfonated poly ether ether ketone chelated with Cu2+ as a proton exchange membrane at sub-zero temperatures.

Improving the proton conductivity (σ) of proton exchange membranes at low temperatures is very important for expanding their application areas. Here, sulfonated poly ether ether ketone (SPEEK) membranes were prepared with different sulfonation degrees, and its maximum ion exchange capacity is 3.15 mmol/g for 10 h at 60 °C. Highly sulfonated SPEEK membrane exhibits ultra-high water uptake and excellent proton conductivity of 0.074 S/cm at -25 °C due to its abundant -SO3H. Nevertheless, its high swelling ratio and low mechanical strength are not conducive to the practical application of the membrane. Luckily, by employing the chelation of Cu2+ with -SO3- on the SPEEK chain, Cu2+-coordinated SPEEK membranes were prepared, and they not only retain high -SO3H content but also possess robust mechanical properties and good dimensional stability compared to pristine SPEEK membrane. Meanwhile, the σ of the SPEEK-Cu membrane reaches 0.054 S/cm at -25 °C, and its fuel cell maximum power (Wmax) reaches 0.42 W/cm2 at -10 °C, demonstrating superior low-temperature performance in comparison to other reported materials. Particularly, water states in the prepared membranes are quantified by low-temperature differential scanning calorimetry. Because much more water bound to the plentiful -SO3H and Cu2+ inside the membrane endows it with anti-freezing performance, the decay of the σ and the Wmax for the SPEEK-Cu membrane is retarded at sub-zero temperatures. It is envisioned that composite membranes comprising metal ions such as Cu2+-SPEEK have a high potential for sub-zero fuel cell applications.

Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning.

The synthesis of steroids is challenging through multistep steroidal core modifications with high site-selectivity and productivity. In this work, a novel enzymatic cascade system was constructed for synthesis of testolactone by specific C17 lactonization/Δ1-dehydrogenation from inexpensive androstenedione using an engineered polycyclic ketone monooxygenase (PockeMO) and an appropriate 3-ketosteroid-Δ1-dehydrogenase (ReKstD). The focused saturation mutagenesis in the substrate binding pocket was implemented for evolution of PockeMO to eliminate the bottleneck effect. A best mutant MU3 (I225L/L226V/L532Y) was obtained with 20-fold higher specific activity compared to PockeMO. The catalytic efficiency (kcat/Km) of MU3 was 171-fold higher and the substrate scope shifted to polycyclic ketones. Molecular dynamic simulations suggested that the activity was improved by stabilization of the pre-lactonization state and generation of productive orientation of 4-AD mediated by distal L532Y mutation. Based on that, the three genes, MU3, ReKstD and a ketoreductase for NADPH regeneration, were rationally integrated in one cell via expression fine-tuning to form the efficient single cell catalyst E. coli S9. The single whole-cell biocatalytic process was scaled up and could generate 9.0 g/L testolactone with the high space time yield of 1 g/L/h without steroidal by-product, indicating the potential for site-specific and one-pot synthesis of steroid.

Study on the Application Performance of Polymer Electrolyte Membrane Functionalized with Triethyl Phosphite-Modified Graphene Oxide in Fuel Cells.

In this paper, we successfully synthesize phosphoric acid functionalized graphene oxide (PGO) based on acid modification of graphene oxide. The composite membrane is further prepared by adding PGO into sulfonated poly(aryl ether ketone sulfone) containing carboxyl groups matrix (C-SPAEKS). The PGO as well as the composite membranes were characterized by a series of tests. The prepared composite proton exchange membranes (PEMs) have good mechanical and electrochemical properties. Compared to the C-SPAEKS membrane, the best composite membrane has a tensile strength of 40.7 MPa while exhibiting superior proton conductivity (110.17 mS cm-1 at 80 °C). In addition, the open-circuit voltage and power density of C-SPAEKS@1% PGO are 0.918 V and 792.17 mW cm-2, respectively. Compared with C-SPAEKS (0.867 V and 166 mW cm-2), it can be seen that our work has a certain effect on the improvement of the single cell performance. The above results demonstrate that the functionalized graphene oxide has greatly improved the electrochemical performance and even the overall performance of PEMs.