Explore the vast range of titles available.

Single-atom catalysts (SACs) have sparked broad interest recently while the low metal loading poses a big challenge for further applications. Herein, a dual protection strategy has been developed to give high-content SACs by nanocasting SiO 2 into porphyrinic metal–organic frameworks (MOFs). The pyrolysis of SiO 2 @MOF composite affords single-atom Fe implanted N-doped porous carbon (Fe SA –N–C) with high Fe loading (3.46 wt%). The spatial isolation of Fe atoms centered in porphyrin linkers of MOF sets the first protective barrier to inhibit the Fe agglomeration during pyrolysis. The SiO 2 in MOF provides additional protection by creating thermally stable FeN 4 /SiO 2 interfaces. Thanks to the high-density Fe SA sites, Fe SA –N–C demonstrates excellent oxygen reduction performance in both alkaline and acidic medias. Meanwhile, Fe SA –N–C also exhibits encouraging performance in proton exchange membrane fuel cell, demonstrating great potential for practical application. More far-reaching, this work grants a general synthetic methodology toward high-content SACs (such as Fe SA , Co SA , Ni SA ). Single-atom catalysts (SACs) with high metal loading are highly desired to improve catalytic performance. Here, the authors report a dual protection strategy by nanocasting SiO 2 into metal–organic frameworks to prepare high-loading SACs with excellent catalytic performance toward oxygen reduction.

Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales , H 2 S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales , as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism. Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.

Background Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of global liver disease that is associated with the rising prevalence of obesity worldwide. There is now increasing clinical and mechanistic evidence reporting on the metabolic and weight loss effects of bariatric surgery on improving NAFLD in obese patients. Objectives The aim of this paper was to quantify the effects of bariatric surgery on NAFLD by appraising the modulation between pre- and post-operative liver enzyme levels (as markers of liver injury) and liver histology. Methods A systematic review of studies reporting pre-operative and post-operative liver enzymes or liver histology was done in obese patients with NAFLD undergoing bariatric surgery. Data were meta-analysed using random-effects modelling. Subgroup analysis, quality scoring and risk of bias were assessed. Results Bariatric surgery is associated with a significant reduction in the weighted incidence of a number of histological features of NAFLD including steatosis (50.2 and 95 %CI of 35.5–65.0), fibrosis (11.9 and 95 %CI of 7.4–16.3 %), hepatocyte ballooning (67.7 and 95 %CI 56.9–78.5) and lobular inflammation (50.7 and 95 %CI 26.6–74.8 %). Surgery is also associated with a reduction in liver enzyme levels, with statistically significant reductions in ALT (11.36 u/l, 95 %CI 8.36–14.39), AST (3.91 u/l, 95 %CI 2.23–5.59), ALP (10.55 u/l, 95 %CI 4.40–16.70) and gamma-GT (18.39 u/l, 95 %CI 12.62–24.16). Heterogeneity in results was high. Conclusions Bariatric surgery is associated with a significant improvement in both histological and biochemical markers of NAFLD. Future studies must focus on higher levels of evidence to better identify the benefits of bariatric surgery on liver disease in order to enhance future treatment strategies in the management of NAFLD.

Lipase is involved in lipid hydrolysis, which is related to nematodes' energy reserves and stress resistance. However, the role of lipases in Bursaphelenchus xylophilus, a notorious plant‐parasitic nematode responsible for severe damage to pine forest ecosystems, remains largely obscure. Here, we characterized a class III lipase as a candidate effector and named it BxLip‐3. It was transcriptionally up‐regulated in the parasitic stages of B. xylophilus and specifically expressed in the oesophageal gland cells and the intestine. In addition, BxLip‐3 suppressed cell death triggered by the pathogen‐associated molecular patterns PsXEG1 and BxCDP1 in Nicotiana benthamiana, and its Lipase‐3 domain is essential for immunosuppression. Silencing of the BxLip‐3 gene resulted in a delay in disease onset and increased the activity of antioxidant enzymes and the expression of pathogenesis‐related (PR) genes. Plant chitinases are thought to be PR proteins involved in the defence system against pathogen attack. Using yeast two‐hybrid and co‐immunoprecipitation assays, we identified two class I chitinases in Pinus thunbergii, PtChia1‐3 and PtChia1‐4, as targets of BxLip‐3. The expression of these two chitinases was up‐regulated during B. xylophilus inoculation and inhibited by BxLip‐3. Overall, this study illustrated that BxLip‐3 is a crucial virulence factor that plays a critical role in the interaction between B. xylophilus and host pine. The Bursaphelenchus xylophilus candidate effector BxLip‐3 is a crucial virulence factor that interacts with two class I chitinases, PtChia1‐3 and PtChia1‐4, in Pinus thunbergii to attenuate host defences.

AMP-activated protein kinase (AMPK) is capable of regulating cellular energy homeostasis and mitochondrial homeostasis. The activation of AMPK can ameliorate metabolic-associated fatty liver disease (MAFLD). An increasing number of studies have demonstrated that AMPK is a crucial enzyme in the regulation of glucose and lipid metabolism in the body, and numerous botanical drugs act as AMPK activators. This activation can alleviate glucose and lipid metabolism disorders, reduce oxidative stress, and serve as a pivotal therapeutic target for metabolic diseases. MAFLD represents the liver-related manifestation of metabolic syndrome. Currently, there are well - established antidiabetic drugs in clinical practice, yet they also entail side effects. A substantial number of in vitro and in vivo experimental studies have indicated that natural traditional Chinese medicine targeting AMPK holds promising prospects in the treatment of MAFLD. In this paper, literature was retrieved through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). Therefore, with AMPK as the target, this article analyzes and summarizes the process and mechanism by which botanical drugs activate AMPK to improve glucose and lipid metabolism disorders and mitochondrial homeostasis disorders, aiming to offer a broader perspective for the development of botanical drugs for MAFLD.

The plant‐parasitic nematode Bursaphelenchus xylophilus, the causal agent of pine wilt disease (PWD), causes enormous economic loss every year. Currently, little is known about the pathogenic mechanisms of PWD. Several effectors have been identified in B. xylophilus, but their functions and host targets have yet to be elucidated. Here, we demonstrated that BxSCD1 suppresses cell death and inhibits B. xylophilus PAMP BxCDP1‐triggered immunity in Nicotiana benthamiana and Pinus thunbergii. BxSCD1 was transcriptionally upregulated in the early stage of B. xylophilus infection. In situ hybridization experiments showed that BxSCD1 was specifically expressed in the dorsal glands and intestine. Cysteine residues are essential for the function of BxSCD1. Transient expression of BxSCD1 in N. benthamiana revealed that it was primarily targeted to the cytoplasm and nucleus. The morbidity was significantly reduced in P. thunbergii infected with B. xylophilus when BxSCD1 was silenced. We identified 1‐aminocyclopropane‐1‐carboxylate oxidase 1, the actual ethylene‐forming enzyme, as a host target of BxSCD1 by yeast two‐hybrid and coimmunoprecipitation. Overall, this study illustrated that BxSCD1 played a critical role in the B. xylophilus–plant interaction. BxSCD1 suppressed plant immunity in Nicotiana benthamiana and Pinus thunbergii. We report for the first time that BxSCD1 interacts with an ethylene‐forming enzyme in pine.

MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a \"seedless\" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers.

Background Bursaphelenchus xylophilus is the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN). Results We cloned, characterized and functionally validated the B. xylophilus effector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 of B. xylophilus . An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine of B. xylophilus . Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number of B. xylophilus and morbidity of pine were significantly reduced in Pinus thunbergii infected with B. xylophilus when BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 in P. thunbergii . Conclusions This study illustrated that BxML1 plays a critical role in the B. xylophilus –plant interaction and virulence of B. xylophilus.

Background The pine wood nematode (PWN), Bursaphelenchus xylophilus , is a devastating pathogen of many Pinus species in China. The aim of this study was to understand the interactive molecular mechanism of PWN and its host by comparing differentially expressed genes and candidate effectors from three transcriptomes of B. xylophilus at different infection stages. Results In total, 62, 69 and 46 candidate effectors were identified in three transcriptomes (2.5 h postinfection, 6, 12 and 24 h postinoculation and 6 and 15 d postinfection, respectively). In addition to uncharacterized pioneers, other candidate effectors were involved in the degradation of host tissues, suppression of host defenses, targeting plant signaling pathways, feeding and detoxification, which helped B. xylophilus survive successfully in the host. Seven candidate effectors were identified in both our study and the B. xylophilu s transcriptome at 2.5 h postinfection, and one candidate effector was identified in all three transcriptomes. These common candidate effectors were upregulated at infection stages, and one of them suppressed pathogen-associated molecular pattern (PAMP) PsXEG1-triggered cell death in Nicotiana benthamiana. Conclusions The results indicated that B. xylophilus secreted various candidate effectors, and some of them continued to function throughout all infection stages. These various candidate effectors were important to B. xylophilus infection and survival, and they functioned in different ways (such as breaking down host cell walls, suppressing host defenses, promoting feeding efficiency, promoting detoxification and playing virulence functions). The present results provide valuable resources for in-depth research on the pathogenesis of B. xylophilus from the perspective of effectors.

Resistant starch (RS) has received increased attention due to its potential health benefits. This study was aimed to investigate the effects of dietary corn RS on immunological characteristics of broilers. A total of 320 broiler chicks were randomly allocated to five dietary treatments: normal corn–soyabean (NC) diet group, corn starch diet group, 4 %, 8 % and 12 % RS diet groups. This trial lasted for 42 d. The relative weights of spleen, thymus and bursa, the concentrations of nitric oxide (NO) and IL-4 in plasma at 21 d of age, as well as the activities of total nitric oxide synthase (TNOS) and inducible nitric oxide synthase (iNOS) in plasma at 21 and 42 d of age showed positive linear responses (P < 0·05) to the increasing dietary RS level. Meanwhile, compared with the birds from the NC group at 21 d of age, birds fed 4 % RS, 8 % RS and 12 % RS diets exhibited higher (P < 0·05) relative weight of bursa and concentrations of NO and interferon-γ in plasma. Birds fed 4 % RS and 8 % RS diets showed higher (P < 0·05) number of IgA-producing cells in the jejunum. While compared with birds from the NC group at 42 d of age, birds fed 12 % RS diet showed higher (P < 0·05) relative weight of spleen and activities of TNOS and iNOS in plasma. These findings suggested that dietary corn RS supplementation can improve immune function in broilers.