The mechanism of water oxidation using transition metal-based heterogeneous electrocatalysts.

The water oxidation reaction, a crucial process for solar energy conversion, has garnered significant research attention. Achieving efficient energy conversion requires the development of cost-effective and durable water oxidation catalysts. To design effective catalysts, it is essential to have a fundamental understanding of the reaction mechanisms. This review presents a comprehensive overview of recent advancements in the understanding of the mechanisms of water oxidation using transition metal-based heterogeneous electrocatalysts, including Mn, Fe, Co, Ni, and Cu-based catalysts. It highlights the catalytic mechanisms of different transition metals and emphasizes the importance of monitoring of key intermediates to explore the reaction pathway. In addition, advanced techniques for physical characterization of water oxidation intermediates are also introduced, for the purpose of providing information for establishing reliable methodologies in water oxidation research. The study of transition metal-based water oxidation electrocatalysts is instrumental in providing novel insights into understanding both natural and artificial energy conversion processes.

A joint analysis of accessibility and household trip frequencies by travel mode.

This paper examines the endogenous relationship between residential level of accessibility and household trip frequencies to tease out the direct and indirect effects of observed behavioural differences. We estimate a multivariate ordered probit model system, which allows dependence in both observed and unobserved factors, using data from the 2016 Transportation Tomorrow Survey (TTS), a household travel survey in the Greater Golden Horseshoe Area (GGH) in Toronto. The modelling framework is used to analyse the influence of exogenous variables on eight outcome variables of accessibility levels and trip frequencies by four modes (auto, transit, bicycle and walk), and to explore the nature of the relationships between them. The results confirm our hypothesis that not only does a strong correlation exist between the residential level of accessibility and household trip frequency, but there are also direct effects to be observed. The complementarity effect between auto accessibility and transit trips, and the substitution effect observed between transit accessibility and auto trips highlight the residential neighbourhood dissonance of transit riders. It shows that locations with better transit service are not necessarily locations where people who make more transit trips reside. Essentially, both jointness (due to error correlations) as well as directional effects observed between accessibility and trip frequencies of multiple modes offer strong support for the notion that accessibility and trip frequency by mode constitute a bundled choice and need to be considered as such.

Covalent Tethering of Cobalt Porphyrins on Phenolic Resins for Electrocatalytic Oxygen Reduction and Evolution Reactions.

The front cover artwork is provided by Rui Cao's group at Shaanxi Normal University. The image shows the design of Co-porphyrin-engineered phenolic resins with intramolecular phenolic hydroxyl groups to facilitate proton and electron transfers for efficient oxygen electrocatalysis, which is bioinspired by cytochrome c oxidases, and shows the excellent performance of Zn-air batteries assembled with the hybrid material. Read the full text of the Research Article at 10.1002/cphc.202400017.

Covalent Tethering of Cobalt Porphyrins on Phenolic Resins for Electrocatalytic Oxygen Reduction and Evolution Reactions.

Using functionalized supporting materials for the immobilization of molecular catalysts is an appealing strategy to improve the efficiency of molecular electrocatalysis. Herein, we report the covalent tethering of cobalt porphyrins on phenolic resins (PR) for improved electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). A cobalt porphyrin bearing an alkyl bromide substituent was covalently tethered on phenolic resins, through the substitution reaction of alkyl bromides with phenolic hydroxyl groups, to afford molecule-engineered phenolic resins (Co-PR). The resulted Co-PR was efficient for electrocatalytic ORR and OER by displaying an ORR half-wave potential of E1/2=0.78 V versus RHE and an OER overpotential of 420 mV to get 10 mA/cm2 current density. We propose that the many residual phenolic hydroxyl groups on PR will surround the tethered Co porphyrin and play critical roles in facilitating proton and electron transfers. Importantly, Co-PR outperformed unmodified PR and PR loaded with Co porphyrins through simple physical adsorption (termed Co@PR). The zinc-air battery assembled using Co-PR displayed a performance comparable to that using Pt/C+Ir/C. This work is significant to present phenolic resins as a functionalized material to support molecular electrocatalysts and demonstrate the strategy to improve molecular electrocatalysis with the use of phenolic resin residues.

Bioactive steroids from seed germination supporting fungus (Ceratobasidium GS2) of the terrestrial orchid Gymnadenia conopsea.

Almost all orchids rely on mycorrhizal fungus to support their seed germination. To date, the effect of active components in mycorrhizal fungus on orchid seed germination largely remains unknown. In this study, we aimed to investigate the impact of active components found in mycorrhizal fungus on orchid seed germination. Specifically, we focused on a terrestrial orchid Gymnadenia conopsea and its host-specific seed germination supporting fungus Ceratobasidium GS2. In total, several steroids (1-7) were isolated from this fungus. Notably, compounds 1, 2, 4, and 5 exhibited significant enhancements in protocorm volume. Moreover, compounds 1-6 demonstrated strong promotion of protocorm differentiation. These findings suggest that steroids may play a crucial role in the symbiotic germination of G. conopsea seeds. Future studies should continue to explore the specific mechanisms through which these steroids exert their effects, contributing to our understanding of orchid biology and mycorrhizal interaction.

Artificial intelligence-driven prediction of multiple drug interactions.

When a drug is administered to exert its efficacy, it will encounter multiple barriers and go through multiple interactions. Predicting the drug-related multiple interactions is critical for drug development and safety monitoring because it provides foundations for practical, safe compatibility and rational use of multiple drugs. With the progress of artificial intelligence (AI) technology, a variety of novel prediction methods for single interaction have emerged and shown great advantages compared to the traditional, expensive and time-consuming laboratory research. To promote the comprehensive and simultaneous predictions of multiple interactions, we systematically reviewed the application of AI in drug-drug, drug-food (excipients) and drug-microbiome interactions. We began by outlining the model methods, evaluation indicators, algorithms and databases commonly used to build models for three types of drug interactions. The models based on the metabolic enzyme P450, drug similarity and drug targets have empathized among the machine learning models of drug-drug interactions. In particular, we discussed the limitations of current approaches and identified potential areas for future research. It is anticipated the in-depth review will be helpful for the development of the next-generation of systematic prediction models for simultaneous multiple interactions.

Systematic analysis of the mechanism of Xiaochaihu decoction in hepatitis B treatment via network pharmacology and molecular docking.

Hepatitis B (HB) is a globally prevalent infectious disease caused by the HB virus. Xiaochaihu decoction (XCHD) is a classic herbal formula with a long history of clinical application in treating HB. Although the anti-HB activity of XCHD has been reported, systematic research on the exact mechanism of action is lacking. Here, a network pharmacology-based approach was used to predict the active components, important targets, and potential mechanism of XCHD in HB treatment. Investigation included drug-likeness evaluation; absorption, distribution, metabolism, and elimination (ADME) screening; protein-protein interaction (PPI) network construction and cluster analysis; Gene Ontology (GO) analysis; and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. Molecular docking was adopted to investigate the interaction between important target proteins and active components. Eighty-seven active components of XCHD and 155 anti-HB targets were selected for further analysis. The GO enrichment and similarity analysis results indicated that XCHD might perform similar or the same GO functions. Glycyrrhizae Radix (GR), one of the seven XCHD herbs, likely exerts some unique GO functions such as the regulation of interleukin-12 production, positive regulation of interleukin-1 beta secretion, and regulation of the I-kappaB/NF-kappaB complex. The PPI network and KEGG pathway analysis results showed that XCHD affects HB mainly through modulating pathways related to viral infection, immunity, cancer, signal transduction, and metabolism. Additionally, molecular docking verified that the active compounds (quercetin, chrysin, and capsaicin) could bind with the key targets. This work systematically explored the anti-HB mechanism of XCHD and provides a novel perspective for future pharmacological research.

Contribution of Social Influences through Superposition of Visual and Olfactory Inputs to Circadian Re-entrainment.

Circadian patterns of locomotor activity are influenced by social interactions. Studies on insects highlight the importance of volatile odors and the olfactory system. Wild-type Drosophila exhibit immediate re-entrainment to new light:dark (LD) cycles, whereas cryb and jetc mutants show deficits in re-entrainability. We found that both male mutants re-entrained faster to phase-shifted LD cycles when social interactions with WT female flies were promoted than the isolated males. In addition, we found that accelerated re-entrainment mediated by social interactions depended on both visual and olfactory cues, and the effect of both cues presented jointly was nearly identical to the sum of the effects of the two cues presented separately. Moreover, we found that re-entrainment deficits in period (per) expression-oscillation in jetc mutants were partially restored by promoting social interactions. Our results demonstrated that, in addition to olfaction, social interactions through the visual system also play important roles in clock entrainment.

Pilose antler polypeptides ameliorate inflammation and oxidative stress and improves gut microbiota in hypoxic-ischemic injured rats.

Pilose antler polypeptides (PAP) have recently been found to be effective in the treatment of brain damage in hypoxic-ischemic encephalopathy (HIE). However, the impacts of hypoxic-ischemic (HI)-induced injury on oxidative stress and inflammation in peripheral tissues remain unclear. In the present study, we hypothesized that the administration of PAP might exert a protective effect on HI-induced peripheral tissue dysfunction. To that end, HI-injured rats were administered PAP for 3 weeks, and then the metabolic phenotypes and gut microbiota were evaluated by qPCR and 16S rRNA sequencing analysis. Hepatic lipid accumulation, systemic oxidative stress and inflammation, as well as impaired gut barrier function and altered gut microbiota were found in HI-injured rats, which were reversed by the treatment of PAP. PAP treatment modulated the abundance and composition of gut microbiota, and PICRUSt analyses revealed that PAP treatment also led to a functional change in the microbial communities. These protective effects of PAP were associated with attenuated susceptibility to bacterial infections, decreased antibiotic synthesis and changed cellular processes and signaling, which may cause inflammation, barrier dysfunction, oxidative stress and mitochondria dysfunction in HI rats. In conclusion, these results suggested that PAP protected against HI-induced peripheral tissue damage in rats and therefore might be a potential candidate for the treatment of HIE and its complications.

Control of Sleep Onset by Shal/Kv4 Channels in Drosophila Circadian Neurons.

Sleep is highly conserved across animal species. Both wake- and sleep-promoting neurons are implicated in the regulation of wake-sleep transition at dusk in Drosophila However, little is known about how they cooperate and whether they act via different mechanisms. Here, we demonstrated that in female Drosophila, sleep onset was specifically delayed by blocking the Shaker cognate L channels [Shal; also known as voltage-gated K+ channel 4 (Kv4)] in wake-promoting cells, including large ventral lateral neurons (l-LNvs) and pars intercerebralis (PI), but not in sleep-promoting dorsal neurons (DN1s). Delayed sleep onset was also observed in males by blocking Kv4 activity in wake-promoting neurons. Electrophysiological recordings show that Kv4 channels contribute A-type currents in LNvs and PI cells, but are much less conspicuous in DN1s. Interestingly, blocking Kv4 in wake-promoting neurons preferentially increased firing rates at dusk ∼ZT13, when the resting membrane potentials and firing rates were at lower levels. Furthermore, pigment-dispersing factor (PDF) is essential for the regulation of sleep onset by Kv4 in l-LNvs, and downregulation of PDF receptor (PDFR) in PI neurons advanced sleep onset, indicating Kv4 controls sleep onset via regulating PDF/PDFR signaling in wake-promoting neurons. We propose that Kv4 acts as a sleep onset controller by suppressing membrane excitability in a clock-dependent manner to balance the wake-sleep transition at dusk. Our results have important implications for the understanding and treatment of sleep disorders such as insomnia.SIGNIFICANCE STATEMENT The mechanisms by which our brains reversibly switch from waking to sleep state remain an unanswered and intriguing question in biological research. In this study, we identified that Shal/Kv4, a well known voltage-gated K+ channel, acts as a controller of wake-sleep transition at dusk in Drosophila circadian neurons. We find that interference of Kv4 function with a dominant-negative form (DNKv4) in subsets of circadian neurons specifically disrupts sleep onset at dusk, although Kv4 itself does not exhibit circadian oscillation. Kv4 preferentially downregulates neuronal firings at ZT9-ZT17, supporting that it plays an essential role in wake-sleep transition at dusk. Our findings may help understand and eventually treat sleep disorders such as insomnia.

Protective effects of astaxanthin on a combination of D-galactose and jet lag-induced aging model in mice.

Oxidative stress caused free radical and mitochondrial damage plays a critical role in the progression of aging and age-related damage at the cellular and tissue levels. Antioxidant supplementation has received growing attention and the effects of antioxidant on aging are increasingly assessed in both animal and human studies. However, additional and more promising treatments that contribute to the expansion of anti-aging therapies are needed. Astaxanthin, a super antioxidant carotenoid and free radical scavenger, inhibits lipid peroxidation more potently than vitamin E. In the present study, we investigated the preventative effects of astaxanthin on aging using an accelerated aging model: mice chronically treated with a combination of D-galactose and jet lag. After 6 weeks of treatment, astaxanthin administration tended to protect the liver weight loss in aged mice. It is probably by upregulating the mRNA expression of galactose-1-phosphate uridyltransferase, which contribute to the enhancement of D-galactose metabolism. Astaxanthin supplementation also improved muscle endurance of aged mice in a swimming test. These results were associated with reduced oxidative stress in serum and increased anti-oxidative enzymes activities and mRNA expression in vivo. Moreover, astaxanthin reversed the dysregulation of aging-related gene expression caused by the combination of D-galactose and jet lag in the liver and kidney of mice. In conclusion, astaxanthin prevents liver weight loss, ameliorates locomotive muscular function, exerts significant anti-aging effects by reducing oxidative stress and improving the expression of age-related genes in D-galactose and jet lag-induced aging model.

The involvement of sympathetic nervous system in essence of chicken-facilitated physiological adaption and circadian resetting.

AIM: The impact of the sympathetic nervous system (SNS) on the regulation of circadian rhythm and physiological functions is still not clear. Previous studies have found that essence of chicken (EC) supplementation facilitated the physiological adaption and circadian resetting in rats subjected to jet lag. Herein, the effects of SNS on the circadian clock and the hypothesis that EC-induced acceleration of circadian resetting is dependent on the SNS are investigated. MAIN METHODS: Male Wistar rats with superior cervical ganglionectomy (SCGx) were used to investigate the role of the SNS in circadian rhythm and physiological functions. SCGx rats were further fed with or without EC-containing diet for 2 weeks and subjected to artificial jet lag. KEY FINDINGS: Loss of SNS did not affect the circadian rhythm both in the hypothalamic suprachiasmatic nuclei (SCN) and peripheral clocks, including the liver and heart. The serum lipid levels were increased significantly in SCGx rats, together with the up-regulation of lipogenic gene expression in the liver and slight effect on serum hormones. The quicker resetting process of the clock genes in peripheral tissues of EC-fed rats was abolished after SCGx. In contrast, the phase shift of serum melatonin and corticosterone were faster in EC-fed rats, compared to that of control rats. SIGNIFICANCE: The SNS controls different aspects of physiological functions, and it has little effect on circadian system under normal light/dark condition. The effects EC on peripheral circadian synchrony and physiological functions were dependent on, at least partly, through the regulation of sympathetic nerve function.

Pilose antler polypeptides ameliorates hypoxic-ischemic encephalopathy by activated neurotrophic factors and SDF1/CXCR4 axis in rats.

Hypoxic-ischemic encephalopathy (HIE) is a complex condition which is associated with high mortality and morbidity. However, few promising treatments for HIE exist. In the present study, the central objective was to identify the therapeutic effect of pilose antler polypeptides (PAP) on HIE in rats. Sprague-Dawley (SD) rats (14 days old) were used and divided into three groups, including control group, hypoxic-ischemia (HI) group and PAP group. After 21 days of treatment, locomotor activity was improved in PAP-treated rats, brain atrophy was decreased and cerebral edema was mitigated to some extent. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis indicated that PAP administration decreased the expressions of inflammatory cytokines and apoptosis genes in hippocampus compared with HI group. Furthermore, the mRNA expressions of genes related to neurotrophic factors were significantly increased in the hippocampus. In addition, the expressions of oxidative stress markers were all down-regulated after PAP administration. Moreover, PAP up-regulated both the mRNA and protein levels of SDF1 and CXCR4, which may activate the SDF1/CXCR4 axis to moderate brain injury. These results suggest that PAP may be potentially used in the treatment of HIE.

Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats.

AIM: Glucocorticoids (GCs), steroid hormones synthetized by the adrenal gland, are regulated by circadian cycles, and dysregulation of GC signaling can lead to the development of metabolic syndrome. The effects and potential mechanism of GCs in physiology were investigated in the present study. MAIN METHODS: Male Wistar rats were orally administered dexamethasone sodium phosphate (DEX, 0.01 and 0.05mg/kg body weight per day) for 7weeks. KEY FINDING: DEX treatment attenuated body weight gain and reduced food intake, whereas it induced the accumulation of fat. Administration of DEX induced dysregulation of the expression of lipogenic genes in both fat and liver. Moreover, the mRNA levels of genes related to mitochondrial biogenesis and function were significantly downregulated in the liver and fat of DEX-treated rats. Furthermore, DEX treatment caused a significant reduction in the richness and diversity of the microbiota in the colon, as assessed using high-throughput sequencing of the 16s rRNA gene V3-V4 region, an increase in inflammatory cell infiltration, and a decrease in mucus secretion in the colon. Additionally, DEX administration induced phase shift or loss of circadian rhythmicity of clock-related genes in peripheral tissues. These results were associated with higher serum corticosterone levels and upregulation of GC receptor (GR) expression in peripheral tissues. SIGNIFICANCE: Our findings indicate that long-term administration of GC caused lipid accumulation, changes in the structure of the intestinal flora, and reduced colonic mucus secretion in vivo. The mechanism of these physiological changes may involve a circadian rhythm disorder and dysregulation of GR expression.

Timing of glucocorticoid administration determines severity of lipid metabolism and behavioral effects in rats.

Glucocorticoids (GCs) are a group of steroid hormones secreted by the adrenal glands in circadian cycles, and the dysregulation of GC signaling has been suggested to cause metabolic syndrome. Even though prolonged GC exposure is associated with serious side effects such as metabolic syndrome and central nervous system disorders, the use of GCs in anti-inflammatory and immunosuppressive therapies has been continuously rising. Meanwhile, the exact mechanisms by which GCs can influence the lipid metabolism as well as behavior and how they are affected by time remain unknown. In this study, the effects of two different long-term GC dosing regimens on lipid metabolism and behavior were investigated. Male Wistar rats received daily administrations of the GC dexamethasone sodium phosphate (DEX, 0.5 mg/kg body weight) at either ZT0 (Dex0) or ZT12 (Dex12). After 6 weeks of treatment, DEX-treated rats, especially those treated at ZT0, had higher hepatic lipid accumulation and serum triglyceride levels and less locomotor activity than did control rats. In addition, serum levels of corticosterone, 5-hydroxy tryptamine and norepinephrine were decreased in the Dex0 group but not in the Dex12 group compared to the control group. Furthermore, quantitative real-time polymerase chain reaction analysis indicated that the chronic administration of GCs at ZT0 upregulated genes related to glycolysis and lipid synthesis and downregulated genes related to fatty acid ß-oxidation in the liver more remarkably than administration at ZT12. Both DEX-treated groups displayed severely altered expression patterns of the core clock genes Bmal1 and Per2 in the liver and in fat. In addition, the expression of glutamate aspartate transporter, glial fibrillary acidic protein and glutamate transporter-1, astrocyte-related genes important for maintaining nervous system functions, was drastically decreased in the hippocampus of DEX-treated rats, especially when DEX was given at ZT0. In conclusion, our findings confirm that the severity of side effects, indicated by altered lipid metabolism and behavioral activity, depends on the timing of GC administration and is associated with the degree of glucocorticoid receptor dysfunction after dosing at disparate time points.