Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty.

Precocious puberty, a pediatric endocrine disorder classified as central precocious puberty (CPP) or peripheral precocious puberty (PPP), is influenced by diet, gut microbiota, and metabolites, but the specific mechanisms remain unclear. Our study found that increased alpha-diversity and abundance of short-chain fatty acid-producing bacteria led to elevated levels of luteinizing hormone and follicle-stimulating hormone, contributing to precocious puberty. The integration of specific microbiota and metabolites has potential diagnostic value for precocious puberty. The Prevotella genus-controlled interaction factor, influenced by complex carbohydrate consumption, mediated a reduction in estradiol levels. Interactions between obesity-related bacteria and metabolites mediated the beneficial effect of seafood in reducing luteinizing hormone levels, reducing the risk of obesity-induced precocious puberty, and preventing progression from PPP to CPP. This study provides valuable insights into the complex interplay between diet, gut microbiota and metabolites in the onset, development and clinical classification of precocious puberty and warrants further investigation.

Mapping of Fatty Aldehydes in the Diabetic Rat Brain Using On-Tissue Chemical Derivatization and Air-Flow-Assisted Desorption Electrospray Ionization-Mass Spectrometry Imaging.

Fatty aldehydes (FALs) are involved in various biological processes, and their abnormal metabolism is related to the occurrence and development of neurological diseases. Because of their low ionization efficiency, methods for in situ detection and mass spectrometry imaging (MSI) analysis of FALs remain underreported. On-tissue chemical tagging of hardly ionizable target analytes with easily ionized moieties can improve ionization efficiency and detection sensitivity in MSI experiments. In this study, an on-tissue chemical derivatization-air-flow-assisted desorption electrospray ionization-MSI method was developed to visualize FALs in the rat brain. The method showed high sensitivity and specificity, allowing the use of in situ high-resolution MS3 to identify FALs. The methodology was applied to investigate the region-specific distribution of FALs in the brains of control and diabetic encephalopathy (DE) rats. In DE rats, FALs were found to be significantly enriched in various brain regions, especially in the cerebral cortex, hippocampus, and amygdala. Thus, increased FAL levels and oxidative stress occurred in a region-dependent manner, which may contribute to cognitive function deficits in DE. In summary, we provide a novel method for the in situ detection of FALs in biological tissues as well as new insights into the potential pathogenesis of DE.

Comparative efficacy and safety of glucose-lowering drugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis.

Objective: Type 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs. Methods: Searches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses. Results: A total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs. Conclusions: The top 10 treatments of type 2 diabetes in children and adolescents aged 10-17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide-2 mcg, sitagliptin+metformin, linagliptin-5 mg, linagliptin-1 mg, metformin, and exenatide-5/10 mcg. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.

Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging.

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

Spatially Resolved Metabolomics Based on Air-Flow-Assisted Desorption Electrospray Ionization-Mass Spectrometry Imaging Reveals Region-Specific Metabolic Alterations in Diabetic Encephalopathy.

Spatially resolved metabolic profiling of brain is vital for elucidating tissue-specific molecular histology and pathology underlying diabetic encephalopathy (DE). In this study, a spatially resolved metabolomic method based on air-flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was developed for investigating the region-specific metabolic disturbances in the brain of DE model rats induced by a high-fat diet in combination with streptozotocin administration. A total of 19 discriminating metabolites associated with glycolysis and the pentose phosphate pathway (PPP); the glutamate/gamma aminobutyric acid-glutamine cycle and tricarboxylic acid cycle; nucleotide metabolism; lipid metabolism; carnitine homeostasis; and taurine, ascorbic acid, histidine, and choline metabolism were identified and located in the brains of the diabetic rats simultaneously for the first time. The results indicated that increased glycolytic and PPP activity; dysfunction of mitochondrial metabolism; dysregulation of adenosinergic, glutamatergic, dopaminergic, cholinergic, and histaminergic systems; disorder of osmotic regulation and antioxidant system; and disorder of lipid metabolism occur in a region-specific fashion in the brains of DE rats. Thus, this study provides valuable information regarding the molecular pathological signature of DE. These findings also underline the high potential of AFADESI-MSI for applications in various central nervous system diseases.

In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging.

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine-creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

2D Metal-Organic Framework Derived CuCo Alloy Nanoparticles Encapsulated by Nitrogen-Doped Carbonaceous Nanoleaves for Efficient Bifunctional Oxygen Electrocatalyst and Zinc-Air Batteries.

The development of efficient bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) still remains a challenge in a wide range of renewable energy technologies. Herein, CuCo alloy nanoparticles encapsulated by nitrogen-doped carbonaceous nanoleaves (CuCo-NC) have been synthesized from a Cu(OH)2 /2D leaf-like zeolitic imidazolate framework (ZIF-L)-pyrolysis approach. Leaf-like Cu(OH)2 is first prepared by the ultrasound-induced self-assembly of Cu(OH)2 nanowires. The efficient encapsulation of Cu(OH)2 in ZIF-L is obtained owing to the morphology fitting between the leaf-like Cu(OH)2 and ZIF-L. CuCo-NC catalysts present superior electrocatalytic activity and stability toward ORR and OER over the commercial Pt/C and IrO2 , respectively, which are further used as bifunctional oxygen electrocatalysts in Zn-air batteries and exhibit impressive performance, with a high peak power density of 303.7 mW cm-2 , large specific capacity of up to 751.4 mAh g-1 at 20 mA cm-2 , and a superior recharge stability.

Cobalt-Nitrogen-Doped Helical Carbonaceous Nanotubes as a Class of Efficient Electrocatalysts for the Oxygen Reduction Reaction.

The oxygen reduction reaction (ORR) is of significant importance in the development of fuel cells. Now, cobalt-nitrogen-doped chiral carbonaceous nanotubes (l/d-CCNTs-Co) are presented as efficient electrocatalysts for ORR. The chiral template, N-stearyl-l/d-glutamic acid, induces the self-assembly of well-arranged polypyrrole and the formation of ordered graphene carbon with helical structures at the molecular level after the pyrolysis process. Co was subsequently introduced through the post-synthesis method. The obtained l/d-CCNTs-Co exhibits superior ORR performance, including long-term stability and better methanol tolerance compared to achiral Co-doped carbon materials and commercial Pt/C. DFT calculations demonstrate that the charges on the twisted surface of l/d-CCNTs are widely separated; as a result the Co atoms are more exposed on the chiral CCNTs. This work gives us a new understanding of the effects of helical structures in electrocatalysis.

Involvement of galanin and galanin receptor 1 in nociceptive modulation in the central nucleus of amygdala in normal and neuropathic rats.

The present study was performed to explore the role of galanin and galanin receptor 1 (GalR 1) in nociceptive modulation in the central nucleus of amygdala (CeA) in normal rats and rats with neuropathy, and the involvement of GalR 1 and PKC was also investigated. The hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations were increased in a dose-dependent manner after intra-CeA injection of galanin in both normal rats and rats with neuropathy. The increased HWLs were significantly attenuated by intra-CeA injection of galanin receptor antagonist M40, indicating an involvement of galanin receptor in nociceptive modulation in CeA. Furthermore, intra-CeA administration of the GalR 1 agonist M 617 induced increases in HWLs in normal rats, suggesting that GalR 1 may be involved in galanin-induce antinociception in CeA. Additionally, intra-CeA injection of the PKC inhibitor inhibited galanin-induced antinociception, showing an involvement of PKC in galanin-induced antinociception in CeA of normal rats. Moreover, there was a significant increase in GalR1 content in CeA in rats with neuropathy than that in normal rats. These results illustrated that galanin induced antinociception in CeA in normal rats and rats with neuropathy, and there is an up-regulation of GalR1 expression in rats with neuropathy.

Association between x-ray repair cross-complementing group 3 (XRCC3) genetic polymorphisms and papillary thyroid cancer susceptibility in a Chinese Han population.

Papillary thyroid cancer (PTC) is a predominant type of thyroid cancer. Ionizing radiation is the only well-established risk factor and may result in double-strand breaks. The x-ray repair cross-complementing group 3 (XRCC3) gene plays a vital role in DNA repair through homologous recombination. We aimed at investigating the association between XRCC3 genetic polymorphisms and PTC susceptibility. Eighty-three PTC patients and 367 controls in a Chinese population were enrolled in the study. Tag single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of XRCC3 SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between XRCC3 SNPs and PTC susceptibility. The statistical analyses were conducted by using SPSS 13.0 software. Four tag-SNPs were initially identified by HaploView 4.2 software. Only one SNP (rs861539) was shown to be significantly associated with increased risk of PTC. There was a significant difference in smoking and drinking status between PTC cases and controls. And the stratified analysis suggested that the polymorphisms of rs861539 in XRCC3 were correlated with PTC risk in the four subgroups of smokers (ex-smokers included), non-smokers, drinkers (ex-drinkers included), and non-drinkers. The meta-analysis showed that only two studies reported a significant association between XRCC3 polymorphisms and PTC risk. In this study, we find a significant association between rs861539 polymorphisms and PTC susceptibility. However, there were inconsistent results in previous published studies. Therefore, further studies in a large population are required to gain insights into the PTC risk conferred by XRCC3 SNPs.