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Sevoflurane is one of the most commonly used volatile anaesthetics for children, but the safety of prolonged or repeated clinical use of sevoflurane in infants or children is controversial. Here, we investigated the effects of sevoflurane on rats in early life and the time scale of those effects. Our behavioral results indicated that repeated short-term exposure of new-born rats to sevoflurane caused learning and memory impairment, while a single exposure of rats to sevoflurane was relatively safe. Further mechanistic investigation revealed that repeated sevoflurane exposure impaired long-term potentiation (LTP), downregulated the expression of certain synaptogenesis-related proteins (GluR1, PSD95) and upregulated proteins related to endoplasmic reticulum (ER) stress in the hippocampus. An ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), reversed the changes in the levels of synaptic plasticity proteins. Our results provide new evidence for the clinical concerns regarding repeated sevoflurane anesthesia.

In the title mononuclear iron(III) complex, [Fe(C15H13N2O3)2]Cl·H2O, the FeIII atom has a distorted octahedral geometry and is six-coordinated by four O atoms and two N atoms from two ligands. In the crystal structure, the complex cations, Cl− anions and water molecules are connected into a chain along [100] through N—H...O, O—H...Cl and N—H...Cl hydrogen bonds. Two adjacent chains are linked by O—H...O hydrogen bonds.

Abstract Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005’s anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically.

Recently, poly(ethylene oxide) (PEO)-based solid polymer electrolytes have been attracting great attention, and efforts are currently underway to develop PEO-based composite electrolytes for next generation high performance all-solid-state lithium metal batteries. In this article, a novel sandwich structured solid-state PEO composite electrolyte is developed for high performance all-solid-state lithium metal batteries. The PEO-based composite electrolyte is fabricated by hot-pressing PEO, LiTFSI and Ti3C2Tx MXene nanosheets into glass fiber cloth (GFC). The as-prepared GFC@PEO-MXene electrolyte shows high mechanical properties, good electrochemical stability, and high lithium-ion migration number, which indicates an obvious synergistic effect from the microscale GFC and the nanoscale MXene. Such as, the GFC@PEO-1 wt% MXene electrolyte shows a high tensile strength of 43.43 ​MPa and an impressive Young's modulus of 496 ​MPa, which are increased by 1205% and 6048% over those of PEO. Meanwhile, the ionic conductivity of GFC@PEO-1 wt% MXene at 60 ​°C reaches 5.01 ​× ​10−2 ​S ​m−1, which is increased by around 200% compared with that of GFC@PEO electrolyte. In addition, the Li/Li symmetric battery based on GFC@PEO-1 wt% MXene electrolyte shows an excellent cycling stability over 800 ​h (0.3 ​mA ​cm−2, 0.3 ​mAh cm−2), which is obviously longer than that based on PEO and GFC@PEO electrolytes due to the better compatibility of GFC@PEO-1 wt% MXene electrolyte with Li anode. Furthermore, the solid-state Li/LiFePO4 battery with GFC@PEO-1 wt% MXene as electrolyte demonstrates a high capacity of 110.2–166.1 ​mAh g−1 in a wide temperature range of 25–60 ​°C, and an excellent capacity retention rate. The developed sandwich structured GFC@PEO-1 wt% MXene electrolyte with the excellent overall performance is promising for next generation high performance all-solid-state lithium metal batteries.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2−/−) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2−/− mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2−/− mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2−/− mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2−/− mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2−/− mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

IntroductionLactation mastitis seriously severely affects the health of lactating females and their infants, yet the underlying causes of clinical lactation mastitis remain unclear.MethodsIn this study, we used microbiota-humanized mice as a model to investigate the role of gut microbiota in lactation mastitis. We compared the fecal microbiota of lactation mastitis patients and healthy individuals and conducted fecal microbiota transplantation (FMT) experiments in an antibiotic-pretreated mouse model to test whether gut microbes contribute to human lactation mastitis.ResultsOur results showed that gut microbiota diversity was reduced and dysbiosis was present in lactating mastitis patients. FMT from lactation mastitis patients (M-FMT), but not from healthy individuals (H-FMT), to antibiotic-treated mice resulted in lactation mastitis. The inflammation in mice caused by gut microbiota from lactating mastitis patients appears to be pervasive, as hepatocytes from mice that received feces from lactating mastitis patients showed marked swelling. In addition, serum pro-inflammatory factors, including IL-4, IL-17, MPO, IL-6, IL-1β, and TNF-α, were significantly increased in the M-FMT group. The Firmicutes/Bacteroidetes ratio (F/B), a biomarker of gut dysbiosis, was significantly increased in the M-FMT group. At the phylum level, Actinobacteria were significantly increased, and Verrucomicrobia were significantly decreased in the M-FMT group. At the genus level, Ruminococcus and Faecalibacterium were significantly reduced, while Parabacteroides were significantly increased in the feces of both patients with lactation mastitis and M-FMT mice. Moreover, our study revealed an “amplification effect” on microbiota differences and mastitis disease following human-to-mouse FMT.ConclusionCollectively, our findings demonstrate that the gut microbiota in lactating mastitis patients is dysbiotic and contributes to the pathogenesis of mastitis.

The gut microbiota was emerging as critical regulatory elements in shaping the outcome of cancer immunotherapy. However, the underlying mechanisms by which the gut commensal species enhance antitumor immunity remain largely unexplored. Here, we show that the gut microbiota from healthy individuals conferred considerable sensitivity to anti-PD-1 in the colorectal cancer (CRC) tumor-bearing mice, whereas gut microbiota from CRC patients failed to do so. By 16S rRNA gene sequencing, we identified Lactobacillus that was significantly increased in the mice with good response to anti-PD-1, and significantly correlated with anti-tumor immunity. After a series of screening, we isolated a novel Lacticaseibacillus strain, named L. paracasei sh2020. L. paracasei sh2020 showed the most notable anti-tumor immunity in the mice with gut dysbiosis. Mechanistically, the antitumor immune response elicited by L. paracasei sh2020 was dependent on CD8+ T cell. In vitro and in vivo studies revealed that L. paracasei sh2020 stimulation triggered the upregulated expression of CXCL10 in the tumors and subsequently enhanced CD8+ T cell recruitment. Meanwhile, the modulation of gut microbiota caused by L. paracasei sh2020 enhanced its antitumor effect and gut barrier function. Overall, our study offered novel insights into the mechanism by which gut microbiota shaped the outcome of cancer immunotherapy and, more importantly, the novel strain L. paracasei sh2020 might serve as an easy and effective way to promote anti-PD-1 effect in clinical practice.

Abnormal metabolic alterations of cancer cells and the host play critical roles in the occurrence and development of tumors. Targeting cancer cells and host metabolism can provide novel diagnosis indicators and intervention targets for tumors. In recent years, it has been found that gut microbiota is involved in the metabolism of the host and cancer cells. Increasingly, gut microbiome and their metabolites have been demonstrated great influence on the tumor formation, prognosis and treatment. Specific gut microbial composition and metabolites are associated with the status of tumor in the host. Interventions on the gut microbiota can exert the protective effects on the tumor, through the manipulation of structure and its related metabolites. This may be the new approach to improve the efficacy of tumor prevention and treatment. Here, we discuss the effects and the underlying mechanisms of gut microbiota and microbial-derived metabolites in tumor progression and treatment.

Essential hypertension is a leading global public health issue, billions of people suffered from it every year. Recently, multiple evidence suggests that DNA methylation play an important role in regulating blood pressure. Here, we tested the risk for essential hypertension conferred by single nucleotide polymorphisms (SNPs) within DNA methyltransferase 1 (DNMT1). Three loci (rs2228611, rs2228612, and rs16999593) were selected to be analyzed in 3410 cases and 1307 normal controls in southern Chinese aged 60 or above. No significant association with essential hypertension was observed for rs2228612 and rs16999593. A higher risk of essential hypertension was found in the minor A allele of rs2228611 in the codominant and recessive model (P < 0.05). After stratified by sex, this association was found in male but not female. Furthermore, this difference was abolished after BMI adjustment in the whole population and reduced in male. In addition, the mutation rate of rs2228611 was higher in the obesity group compared with the normal weight group of male. Intriguingly, rs2228611 was also a risk factor of essential hypertension in normal weight male. These findings indicated that rs2228611 might contribute to male hypertension via BMI-dependent mechanisms in obesity male and BMI-independent mechanisms in normal weight male.

The adsorption properties of benzene, p-dichlorobenzene and nitrobenzene on polymer nanofibers were studied. Compared with polyacrylonitrile nanofiber, polystyrene (PS) nanofiber presented better adsorption performance. Langmuir and Freundlich adsorption models were used for the mathematical description of adsorption equilibria, and Freundlich isotherms fitted better. Kinetic studies showed that the adsorption of PS nanofiber followed pseudo first-order model. Various thermodynamic parameters such as standard free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) were calculated for predicting the adsorption nature of PS nanofiber for three benzenes, which indicated that the adsorption was spontaneous and a physical process. The regeneration efficiency maintains over 80% after five cycles of adsorption/desorption tests. It showed that PS nanofibers are promising candidates for adsorption and removal of aromatic hydrocarbons from water. [ABSTRACT FROM AUTHOR]

The VHL tumour suppressor gene is lost in approximately 70% of clear cell renal cell carcinoma (ccRCC). In this study, the authors demonstrate that VHL loss in these tumours augments anthracyclines chemotherapy by down-regulation of ALDH2.