The identification of PSEN1 p.Tyr159Ser mutation in a non-canonic early-onset Alzheimer's disease family.

More than 300 missense mutations in PSEN1 gene have been correlated to the early-onset Alzheimer's disease (EOAD), but given the high diversity of PS1 (the PSEN1 gene product) substrates and the involvement of PS1 in multiple biological functions, different mutants may represent different EOAD etiologies, and how each mutant contributes to the EOAD remains to be further investigated. Here we report the identification of a novel PSEN1 p.Tyr159Ser in a family with multiple EOAD cases. The mutant PS1 protein (PS1Y159S) was analyzed for its activity in producing amyloid-ß (Aß) and for the efficiency in maturation in vitro. We also screened other mutations and SNPs that may modify the effect of PSEN1 p.Tyr159Ser on AD pathogenesis. The blood samples of the family were collected for whole-exome gene sequencing and analysis. The identified mutant PS1 and several other PS1 mutants were co-expressed with the APP Swedish mutant to compare the effects on APP processing and PS1 maturation.1. The proband and her siblings over 50 years old showed typical AD or MCI symptoms. Exon sequencing identified the p.Tyr159Ser mutation in the PSEN1 gene. As not until the age of 78 did the proband's mother who carried this mutation displayed the symptoms of uncharacterized neuropsychiatry instead of AD, but all the mutation bearing lower generation developed AD or MCI after the age of 50, we also analyzed mutations/SNPs that are different between the mother and the lower generation. By in vitro assays, we found that the Y159S substitution strongly increased Aß42/Aß40 ratio and significantly affected PS1 maturation. The newly discovered PSEN1 p.Tyr159Ser is an AD-causing mutation, yet, the carriers are not obligated AD patients. Mutations/SNPs in other gene may modify the effects of this mutation, and the identification of these mutations/SNPs may facilitate the discovery of AD-preventing mechanisms and methods.

Synthesis, Optical Properties, and Fluorescence Cell Imaging of Novel Mixed Fluorinated Subphthalocyanines.

Subphthalocyanines (SubPcs) are a kind of tripyrrolic macrocycle with a boron atom at their core. Incorporating different units onto the SubPc periphery can endow them with various unique properties. Herein, a series of novel fluorinated low-symmetry SubPc derivatives containing chlorine groups (F8-Cl4-SubPc, F4-Cl8-SubPc) and methoxy groups (F8-(OCH3)2-SubPc) were synthesized and characterized by spectral methods (MS, FT-IR, 1H, 13C, 11B, and 19F NMR spectroscopy), and the effect of the peripheral substituents on their electronic structure of low-symmetry macrocycle was investigated by cyclic voltammetry, theoretical calculation, electronic absorption, and emission spectroscopy. In contrast to perfluorinated SubPcs, these low-symmetry SubPcs revealed non-degenerate LUMO and LUMO + 1 orbitals, especially F8-(OCH3)2-SubPc, which was consistent with the split Q-band absorptions. The cyclic voltammetry revealed that these SubPcs exhibited two or three reduction waves and one oxidation wave, which is consistent with the reported SubPcs. Finally, an intracellular fluorescence imaging study of these compounds revealed that these compounds could enter cancer cells and be entrapped in the lysosomes, which provides a possibility of future applications in lysosome fluorescence imaging and targeting.

Occludin degradation makes brain microvascular endothelial cells more vulnerable to reperfusion injury in vitro.

Intracerebral hemorrhage is the most dangerous complication in tPA thrombolytic therapy for ischemic stroke, which occurs as a consequence of endothelial cell death at the blood-brain barrier (BBB) during thrombolytic reperfusion. We have previously shown that cerebral ischemia-induced rapid occludin degradation and BBB disruption. Here we demonstrated an important role of occludin degradation in facilitating the evolution of ischemic endothelial cells toward death. Cultured brain microvascular endothelial cells (bEnd.3 cells) were exposed to oxygen-glucose deprivation (OGD) or incubated with occludin siRNA or occludin AAV to achieve an occludin deficiency or over-expression status before exposing to reoxygenation (R) or TNF-α treatment. Cell death was assessed by measuring lactate dehydrogenase release, TUNEL staining, and flow cytometry analysis. Inhibition of OGD-induced occludin degradation with SB-3CT or over-expression of occludin with occludin AAV both significantly attenuated OGD/R-induced apoptosis and pyroptosis in bEnd.3 cells. Consistently, knockdown of occludin with siRNA potentiated TNF-α-induced apoptosis, supporting an important role of occludin integrity in endothelial cell survival. Similar results were observed for pyroptosis, in which occludin knockdown with siRNA led to a significant augmentation of cytokines secretion, inflammasome activation, and pyroptosis occurrence in TNF-α-treated bEnd.3 cells. Lastly, up-regulation of c-Yes, PI3K/AKT, and ERK concurrently occurred with occludin degradation after OGD/R or TNF-α treatment, and the level of these proteins were further increased when inhibition of occludin degradation or over-expression of occludin. These data indicate that occludin degradation inflicted during ischemia makes BBB endothelial cells more vulnerable to reperfusion-associated stress stimuli.

Iron-catalyzed radical cascade 6-endo cyclization of dienes towards fused nitrogen heterocycles initiated by an alkoxycarbonyl radical.

An iron-catalyzed radical cascade cyclization of dienes initiated by an alkoxycarbonyl radical has been developed in the presence of (NH4)2S2O8, leading to a series of fused nitrogen heterocyclic compounds under relatively mild reaction conditions. The reaction is triggered by the addition of an alkyoxycarbonyl radical derived from the cleavage of alkoxyformyl hydrazide. Afterward, the formed nucleophilic radical preferred addition to the electron-neutral vinyl rather than the electron-deficient vinyl, followed by cascade 6-endo cyclization and further radical cyclization.

Rhodium-catalyzed C-H activation/annulation of amidines with 4-diazoisochroman-3-imines toward isochromeno[3,4-c]isoquinolines.

A rhodium-catalyzed C-H activation/annulation of amidines with 4-diazoisochroman-3-imines has been established to afford a series of 8-amino-5H-isochromeno[3,4-c]isoquinolines in moderate to good yields with good functional group tolerance. This reaction proceeded in a sequential C-H activation/carbene migration insertion/intramolecular annulation procedure and featured the construction of a C-C and C-N bond in one pot. UV-vis and fluorescence spectral analyses of these highly fused heteroarenes were performed.

Investigation of the effective components of the flowers of Trollius chinensis from the perspectives of intestinal bacterial transformation and intestinal absorption.

CONTEXT: The flowers of Trollius chinensis Bunge (Ranunculaceae), used for respiratory tract infections, mainly contain flavonoids, phenolic acids, and alkaloids; however, the effective components are debatable because of their unclear in vivo activities. OBJECTIVE: This study investigates the effective components from the perspectives of biotransformation and absorption. MATERIALS AND METHODS: Both single person derived- and multiple people-derived intestinal florae were used to investigate the biotransformation of aqueous extract of the flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0 mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2) monolayers and everted gut sacs were employed to evaluate the intestinal absorption of the intestinal bacterial transformed AEOF at the concentrations of 10, 20, and 30 mg/mL, respectively, for 180 min. RESULTS: 2″-O-ß-l-Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid, proglobeflowery acid, and trolline in AEOF were not transformed by intestinal bacteria, while isoquercetin and trollioside were completely transformed. The Papp values of 2″-O-ß-l-galactopyranosylorientin, orientin, and vitexin calculated based on the experimental data of intestinal absorption were at the levels of 10-5, whereas those of veratric acid, proglobeflowery acid, and trolline were at 10-4. The mass ratio of flavonoids to phenolic acids to alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. DISCUSSION AND CONCLUSION: The dominant position of flavonoids was replaced by phenolic acids after absorption. In addition to flavonoids which are usually considered as the dominant effective ones, phenolic acids and alkaloids should be also very important for the efficacy of these flowers.

DDB2 is involved in ubiquitination and degradation of PAQR3 and regulates tumorigenesis of gastric cancer cells.

DDB2 (damage-specific DNA-binding protein 2) is the product of the xeroderma pigmentosum group E gene which is involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A). PAQR3 (progestin and adipoQ receptor family member III) is a newly discovered tumour suppressor that is implicated in the development of many types of human cancers. In the present paper, we report that DDB2 is involved in ubiquitination and degradation of PAQR3. DDB2 is able to interact with PAQR3 in vivo and in vitro. Both overexpression and knockdown experiments reveal that the protein expression level, protein stability and polyubiquitination of PAQR3 are changed by DDB2. Negative regulation of EGF (epidermal growth factor)- and insulin-induced signalling by PAQR3 is also altered by DDB2. At the molecular level, Lys(61) of PAQR3 is targeted by DDB2 for ubiquitination. The cell proliferation rate and migration of gastric cancer cells are inhibited by DDB2 knockdown and such effects are abrogated by PAQR3 knockdown, indicating that the effect of DDB2 on the cancer cells is mediated by PAQR3. Collectively, our studies not only pinpoint that DDB2 is a post-translational regulator of PAQR3, but also indicate that DDB2 may play an active role in tumorigenesis via regulating PAQR3.

Suppression of miR-221 inhibits glioma cells proliferation and invasion via targeting SEMA3B.

BACKGROUND: Gliomas are the most common primary tumors in the central nervous system. Due to complicated signaling pathways involved in glioma progression, effective targets for treatment and biomarkers for prognosis prediction are still scant. RESULTS: In this study we revealed that a new microRNA (miR), the miR-221, was highly expressed in the glioma cells, and suppression of miR-221 resulted in decreased cellular proliferation, migration, and invasion in glioma cells. Mechanistic experiments validated that miR-221 participates in regulating glioma cells proliferation and invasion via suppression of a direct target gene, the Semaphorin 3B (SEMA3B). The rescue experiment with miR-221 and SEMA3B both knockdown results in significant reversion of miR-221 induced phenotypes. CONCLUSION: Taken together, our findings highlight an unappreciated role for miR-221 and SEMA3B in glioma.

Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology.

The intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the responsible microbes/genes, we developed a metabolomics-based assay to screen 104 commensals and identified candidates that efficiently utilize aa. Using genetics, we identified multiple responsible metabolic genes in phylogenetically diverse microbes. By colonizing germ-free mice with the wild-type strain and their isogenic mutant deficient in individual aa-metabolizing genes, we found that these genes regulate the availability of gut and circulatory aa. Notably, microbiota genes for branched-chain amino acids (BCAAs) and tryptophan metabolism indirectly affect host glucose homeostasis via peripheral serotonin. Collectively, at single-gene level, this work characterizes a microbiota-encoded metabolic activity that affects host nutrient homeostasis and provides a roadmap to interrogate microbiota-dependent activity to improve human health.

Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids.

A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.

[Fluoroquinolone associated myasthenia gravis exacerbation: clinical analysis of 9 cases].

OBJECTIVE: To explore the characteristics of acute exacerbations of myasthenia gravis after fluoroquinolone exposure. METHODS: Gender, age, prior type, absolute score, concurrent disease, precipitated disease, use of antibiotic, onset/symptom/degree of exacerbation, therapeutic measures and prognosis at Month 1 were retrospectively analyzed for 9 patients after fluoroquinolone systemic exposure. RESULTS: Ciprofloxacin (n = 4), levofloxacin (n = 1) and moxifloxacin (n = 4) exposure resulted in myasthenia gravis exacerbation. Myasthenia gravis exacerbations developed at 15 minutes to 4 days post-exposure. And the clinical scores of quantitative myasthenia gravis (QMG) increased by an average of 10. The main syndromes included dyspnea, diplopia, ptosis and dysphagia. All patients improved upon the withdrawal of fluoroquinolone in conjunctions with other interventions. CONCLUSION: Fluoroquinolone exposure may result in myasthenia gravis exacerbations in patients with underlying diseases. Healthcare professionals should be aware of this serious drug-disease association.

Research progress on cognitive impairment and the expression of serum inflammatory markers in patients with white matter hyperintensities: a narrative review.

Background and Objective: White matter hyperintensities (WMH) are magnetic resonance imaging manifestations of brain white matter lesions, which are common in the elderly. There is a correlation between WMH and cognitive impairment, but its imaging features lack heterogeneity, which makes early diagnosis difficult. Studies have found that cognitive impairment in patients with WMH is closely related to changes in the expression of serum inflammatory markers. This article reviews the correlation between WMH and cognitive function, as well as the correlation between cognitive impairment and serum inflammatory markers in patients with WMH. Methods: We searched the China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases to identify studies on the correlation between cognitive impairment and serum inflammatory markers in patients with WMH published between the databases' dates of inception and December 2021. Key Content and Findings: Serum inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor α (TNF-α), plasma lipoprotein phospholipase A2 (Lp-PLA2) and interleukins (ILs) are closely related to cognitive impairment in patients with WMH. Conclusions: CRP, TNF-α, ILs and others systemic inflammatory markers can be used to help diagnose and predict cognitive impairment in WMH patients. But more in-depth and comprehensive research is needed to determine the role of systemic inflammatory markers in diagnosing WMH cognitive impairment.

Gut Parabacteroides merdae protects against cardiovascular damage by enhancing branched-chain amino acid catabolism.

Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and hyperlipidemia through modulating the gut microbiota in obese mice. Here we show that GMD protects against obesity-associated atherosclerosis by increasing the abundance of Parabacteroides merdae in the gut and enhancing branched-chain amino acid (BCAA) catabolism. Administration of live P. merdae to high-fat-diet-fed ApoE-null male mice reduces atherosclerotic lesions and enhances intestinal BCAA degradation. The degradation of BCAAs is mediated by the porA gene expressed in P. merdae. Deletion of porA from P. merdae blunts its capacity to degrade BCAAs and leads to inefficacy in fighting against atherosclerosis. We further show that P. merdae inhibits the mTORC1 pathway in atherosclerotic plaques. In support of our preclinical findings, an in silico analysis of human gut metagenomic studies indicates that P. merdae and porA genes are depleted in the gut microbiomes of individuals with atherosclerosis. Our results provide mechanistic insights into the therapeutic potential of GMD through P. merdae in treating obesity-associated cardiovascular diseases.

Double-Faced Atomic-Level Engineering of Hollow Carbon Nanofibers as Free-Standing Bifunctional Oxygen Electrocatalysts for Flexible Zn-Air Battery.

Flexible solid-state zinc-air batteries (ZABs) with low cost, excellent safety, and high energy density has been considered as one of ideal power sources for portable and wearable electronic devices, while their practical applications are still hindered by the kinetically sluggish cathodic oxygen reduction and oxygen evolution reactions (ORR/OER). Herein, a Janus-structured flexible free-standing bifunctional oxygen electrocatalyst, with OER-active O, N co-coordinated Ni single atoms and ORR-active Co3O4@Co1-xS nanosheet arrays being separately integrated at the inner and outer walls of flexible hollow carbon nanofibers (Ni-SAs/HCNFs/Co-NAs), is reported. Benefiting from the sophisticated topological structure and atomic-level-designed chemical compositions, Ni-SAs/HCNFs/Co-NAs exhibits outstanding bifunctional catalytic activity with the ΔE index of 0.65 V, representing the current state-of-the-art flexible free-standing bifunctional ORR/OER electrocatalyst. Impressively, the Ni-SAs/HCNFs/Co-NAs-based liquid ZAB show a high open-circuit potential (1.45 V), high capacity (808 mAh g-1 Zn), and extremely long life (over 200 h at 10 mA cm-2), and the assembled flexible all-solid-state ZABs have excellent cycle stability (over 80 h). This work provides an efficient strategy for developing high-performance bifunctional ORR/OER electrocatalysts for commercial applications.

Polysaccharides from Lyophyllum decastes reduce obesity by altering gut microbiota and increasing energy expenditure.

Polysaccharides are known to confer protection against obesity via modulation of gut microbiota. To expand our knowledge of mushroom-derived prebiotics, we investigated the structural characteristics and anti-obesity effects of Lyophyllum decastes polysaccharides. Two heteroglycans were purified and characterized. The isolated polysaccharides effectively reduced obesity and the related disorders in the diet-induced obese (DIO) mice. An altered gut microbiota with enrichments of Bacteroides intestinalis and Lactobacillus johnsonii and an increase of secondary bile acids were detected in the polysaccharide-treated mice. Supplementation of B. intestinalis and L. johnsonii prevented the obesity and hyperlipidemia in DIO mice, demonstrating their causal linkage to the efficacy of polysaccharides. An enhancement of energy expenditure in the brown adipose tissues due to up-regulation of the secondary bile acids-activated TGR5 pathway was deduced to be one of the mechanisms underlying the effect of polysaccharides. These results confirmed Lyophyllum decastes-derived polysaccharides as new prebiotics for preventing and treating obesity.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. CASE PRESENTATION: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. CONCLUSIONS: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

Silencing PAQR3 protects against oxygen-glucose deprivation/reperfusion-induced neuronal apoptosis via activation of PI3K/AKT signaling in PC12 cells.

AIMS: Neuronal apoptosis acts as the pivotal pathogenesis of cerebral ischemia/reperfusion (I/R) injury after ischemic stroke. PAQR3 (progestin and adipoQ receptor family member 3) is a crucial player who participates in the regulation of cell death. We aim to explore the specific function and the underlying mechanism of PAQR3 in cerebral I/R induced neuronal injury. MAIN METHODS: We established a mouse middle cerebral artery occlusion/reperfusion (MCAO/R) model and rat adrenal pheochromocytoma (PC12) cell oxygen-glucose deprivation/reperfusion (OGD/R) model to detect the expression and of PAQR3 after I/R treatment in vivo and in vitro. We used lentivirus to knockdown PAQR3 and investigated the function of PAQR3 in I/R induced neuronal apoptosis. KEY FINDINGS: PAQR3 expression is markedly increased in the ischemic hemisphere of C57BL/6 mice and PC12 cells after I/R stimulation. Knockdown PAQR3 can attenuate neuronal apoptosis induced by I/R in PC12 cells and exerts neuroprotective effects. PAQR3 deficiency can significantly raise cell viability and suppress LDH leakage under I/R treatment. Silencing PAQR3 attenuates neuronal apoptosis remarkably with fewer TUNEL-positive cells and lower apoptosis rate under I/R treatment. Mechanistically, knockdown of PAQR3 can inhibit the apoptosis pathway through inducing anti-apoptotic proteins and inhibiting pro-apoptotic proteins. Besides, PI3K/AKT signaling suppression with LY294002 abolished the neuroprotective functions induced by silencing PAQR3. SIGNIFICANCE: Our results elucidate that silencing PAQR3 can protect PC12 from OGD/R injury via activating PI3K/AKT pathway. And therefore, provide a novel therapeutic target for the prevention of cerebral I/R injury.

Intestinal bacteria are involved in Radix Glycyrrhizae and Radix Euphorbiae Pekinensis incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Eighteen Incompatible Medicaments (EIM) belongs to the category of incompatibility of Traditional Chinese medicine (TCM). This theory forbids concomitant using any one of the eighteen herbal pairs such as Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP), Radix Aconiti-Bulbus Fritiliariae Cirrhosae, and Radix et Rhizoma Veratri Nigri-Radix Ginseng. Concomitant using RG and REP could result in more serious adverse effects on major organs such as kidney, heart, and liver. AIM OF THE STUDY: To investigate the effects of RG-REP decoctions on gut microbiota and short-chain fatty acids (SCFAs) for the purpose of elucidating the mechanism of RG-REP incompatibility. MATERIALS AND METHODS: Six groups of male SD rats were intragastrically administrated with distilled water, RG decoction, REP decoction, 1:1 RG-REP decoction, 2:1 RG-REP decoction and 3:1 RG-REP decoction, respectively, twice daily for 30 consecutive days, and the feces of each rat was separately sampled for gut microbiota analysis and SCFAs assay. 16S rDNA sequencing was employed to comparatively investigate the structure and abundance of intestinal bacteria in rat feces. Gas chromatography (GC) was used to quantitatively determine the contents of SCFAs in rat feces and in vitro samples. The correlation between bacteria and the production of SCFAs was analyzed by Spearman correlation analysis. An in vitro model of human intestinal bacteria was also constructed to simulate and validate the in vivo experiment. RESULTS: The contents of butyric acid in both rat feces and in vitro samples decreased in RG-REP groups. The general structure of gut microbiota in RG-REP groups was not significantly different from that in control group. However, RG alone increased the abundance of Lactobacillus while this effect was counteracted by concomitant using with REP. REP alone decreased the abundance of two interrelated species, Akkermansia and Butyricimonas, and this effect was strengthened by concomitant using REP with RG in the ratio of 1:1. In comparison with REP alone, RG-REP combination also significantly increased the abundance of Streptococcus and Prevotella. CONCLUSION: The incompatibility of RG-REP combination is associated with its negative effect against probiotic bacteria and positive effect on conditional pathogenic bacteria as well as its inhibition on butyric acid production.

The gut commensal fungus, Candida parapsilosis, promotes high fat-diet induced obesity in mice.

Gut fungi is known to play many important roles in human health regulations. Herein, we investigate the anti-obesity efficacy of the antifungal antibiotics (amphotericin B, fluconazole and 5-fluorocytosine) in the high fat diet-fed (HFD) mice. Supplementation of amphotericin B or fluconazole in water can effectively inhibit obesity and its related disorders, whereas 5-fluorocytosine exhibit little effects. The gut fungus Candida parapsilosis is identified as a key commensal fungus related to the diet-induced obesity by the culture-dependent method and the inoculation assay with C. parapsilosis in the fungi-free mice. In addition, the increase of free fatty acids in the gut due to the production of fungal lipases from C. parapsilosis is confirmed as one mechanism by which C. parapsilosis promotes obesity. The current study demonstrates the gut C. parapsilosis as a causal fungus for the development of diet-induced obesity in mice and highlights the therapeutic strategy targeting the gut fungi.

Porous MoWN/MoWC@NC Nano-octahedrons synthesized via confined carburization and vapor deposition in MOFs as efficient trifunctional electrocatalysts for oxygen reversible catalysis and hydrogen production in the same electrolyte.

We used a simple MOFs-assisted synthesis strategy based on the encapsulation and in-situ carburizing reaction of Cu-based metallic organic frameworks (NENU-5) to synthesize porous nano-octahedral materials, MoWN/MoWC@NCTs (T = 700, 800, and 900). Together with the vapor deposition strategy, the volatile nitrogen species from the pyrolysis of dicyandiamide were captured by the nano-octahedral materials, and formed tungsten-molybdenum-based carbonitride nanocrystals encapsulated in nitrogen-doped carbon. The porous nano-octahedron has a unique heterostructure composed of Mo2N/MoC/W2N/WC. The representative MoWN/MoWC@NC800 showed trifunctional electrocatalytic activity in oxygen reduction reaction/oxygen evolution reaction/hydrogen evolution reaction (ORR/OER/HER) in an alkaline medium (0.1 M KOH). The total oxygen electrode activity index ΔE = 0.795 V (vs. RHE) was found in OER/ORR, and the material also exhibits excellent HER performance. The minimum potential of -0.17 V (vs. RHE) was provided at a current density of -10 mA cm-2. MoWN/MoWC@NC800 showed excellent cycle stability and durability in ORR/OER/HER with the same electrolyte (0.1 M KOH). More importantly, MoWN/MoWC@NC800 could be used to construct high-performance zinc-air batteries and sued for driving electrocatalytic water splitting in a self-powered manner. The successful preparation of the materials indicate that the synthetic strategy provides new reference ideas for developing functional materials with high catalytic properties for various applications.