Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.

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.

Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease.

BACKGROUND: Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. METHODS: We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. FINDINGS: Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. INTERPRETATION: This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.

Insight into the electrochemical process of EDTA-assisted soil washing effluent under alternating current.

EDTA has been widely utilized as a chelating agent in soil heavy metal remediation, due to its strong coordination capability. Electrochemical deposition is a promising avenue to treat soil washing effluent. However, the impact of advanced electrochemical techniques on EDTA remains incompletely understood. Herein, we present a pioneering approach, utilizing a dual-chamber electrolytic cell and alternating current (AC) power supply. This approach achieves concurrent removal of M-EDTA while efficiently recovering heavy metal and recycling EDTA. Results demonstrate AC displays superior heavy metal removal capability for Cu, Pb, and Cd compare to direct current (DC), with EDTA decomposition mainly occurring in the anolyte. Substituting DC with AC and employing the dual-chamber electrolytic cell significantly enhances EDTA recovery efficiency from 47% to an impressive 96.8%. XPS and Raman spectra reveal an enhanced oxidative surface of the graphite anode under AC, which diminishes the decomposition of EDTA. Long-term experiments validate that this strategy boosts EDTA cyclability to 20 cycles with an outstanding 84% recovery efficiency and negligible electrode corrosion, surpassing the 8 cycles under the traditional strategy. This study innovatively combines cell design and electrochemical techniques, remarkably improving the reusability of EDTA and anode, offering valuable insights for chelate-related applications.

OBMeta: a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases.

MOTIVATION: Gut dysbiosis is closely associated with obesity and related metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The gut microbial features and biomarkers have been increasingly investigated in many studies, which require further validation due to the limited sample size and various confounding factors that may affect microbial compositions in a single study. So far, it lacks a comprehensive bioinformatics pipeline providing automated statistical analysis and integrating multiple independent studies for cross-validation simultaneously. RESULTS: OBMeta aims to streamline the standard metagenomics data analysis from diversity analysis, comparative analysis, and functional analysis to co-abundance network analysis. In addition, a curated database has been established with a total of 90 public research projects, covering three different phenotypes (Obesity, T2D, and NAFLD) and more than five different intervention strategies (exercise, diet, probiotics, medication, and surgery). With OBMeta, users can not only analyze their research projects but also search and match public datasets for cross-validation. Moreover, OBMeta provides cross-phenotype and cross-intervention-based advanced validation that maximally supports preliminary findings from an individual study. To summarize, OBMeta is a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases. AVAILABILITY AND IMPLEMENTATION: OBMeta is freely available at: http://obmeta.met-bioinformatics.cn/.

Applying the Adjusted Chinese Dietary Balance Index-16 to Assess the Dietary Quality of Chinese Postpartum Lactating Mothers.

A balanced diet is considered necessary in maternal recovery and neonatal development; however, the dietary quality of lactating mothers in China has not been systematically evaluated in different regions and stages of lactation. In addition, the release of the Chinese Dietary Guidelines in 2022 implies that the dietary index method needs to be adjusted accordingly. In this study, the adjusted Chinese Dietary Balance Index-16 (DBI-16) was used to assess the dietary quality of lactating women, referred to as the Dietary Balance Index for lactating women (DBI-L). This study is part of the MUAI study, in which dietary intake and demographic characteristics of lactating mothers from six cities in China and at different stages of lactation were obtained through a self-administered questionnaire and a food frequency questionnaire; 2532 puerperal women were included. According to the DBI-L, 66.2% of participants had inadequate dietary intake (79.1% vegetables, 79.1% fruits, 86.7% dairy products, 39.7% soybeans, and 69.4% fish products, respectively), 57.8% had excessive intake (76.0% cereals, 64.4% meat, and 29.1% eggs, respectively) and 92.2% had unbalanced dietary consumption. Dietary quality was optimal for mothers in the first month after delivery, and the dietary quality of mothers in economically developed places such as Shanghai and Guangzhou was significantly better than that in less developed places such as Lanzhou and Changchun. The dietary quality of lactating women in China is imbalanced, with excessive and inadequate dietary intake. The country should strengthen nutritional interventions for lactating mothers, especially in economically underdeveloped regions.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

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.

Recrystallized Resistant Starch: Structural Changes in the Stomach, Duodenum, and Ileum and the Impact on Blood Glucose and Intestinal Microbiome in Mice.

The structure and properties of resistant starch (RS) and its digestive products were assessed in mice. Digestion of recrystallized (group RS3, including RS3a and RS3b) and control RS (RS2, RS4, and RS5) in the stomach, duodenum, and ileum of mice was systematically analyzed along with in vivo digestive degradation of RS3. RS3a and RS3b significantly reduced the release of blood glucose. During in vivo digestion, the proportion of ultrashort and A chains in the RS3a and RS3b digestive residues gradually increased, whereas the proportion of B1 and B2 chains gradually reduced. B3+ chain proportions did not change. The final digestive residues in the ileum (RS3a-I90 and RS3b-I90) maintained a high proportion of suitable chain length, accounting for more than 60%. The crystalline structure of RS3a-I90 was weakened, indicating the hydrolysis of partial crystal structure. In comparison, RS3b-I90 maintained an orderly crystalline structure, indicating its higher resistance to enzymatic hydrolysis. In vivo experiments showed that RS could maintain the normal growth of mice and effectively control weight gain. RS3a significantly increased the concentrations of acetic, propionic, and butyric acids, while reducing the abundance of Firmicutes to Bacteroidetes ratio, further confirming the benefits of RS3 in gastrointestinal health.

Metal-organic frameworks-derived MCo2O4 (M = Zn, Ni, Cu) two-dimensional nanosheets as anodes materials to boost lithium storage.

Transition metal oxides (TMOs) have received significant consideration. Because of their enormous theoretical capacity, cheap, and less toxicity. Notably, cobalt-based materials hold promises as negative electrode materials for batteries, but they suffer from less electrical conductivity and significant volume changes during operation. In order to address these challenges, sacrificial templating techniques at the nanoscale offer a potential solution for improving the electrochemical stability and rate performance of these materials. More specifically, these tactics have proven popular for designing Li-ion storages. To ascertain the impact of multiple metal ions on the electrochemical capacity, metal organic frameworks (MOFs) derived MCo2O4-MOF (M = Zn, Ni, Cu) were developed. Among these, ZnCo2O4 showed the best electrochemical performance (927.2 mAh g-1 at 0.1 A g-1 after 250 cycles). Furthermore, calculations based on density functional theory (DFT) revealed that ZnCo2O4 had the lowest Li+ adsorption energy, with a minimum value of -1.61 eV. Moreover, this research aims to design controllable nanostructures in order to enhance the design of transition bimetallic oxide composites for energy storage applications.

Fecal microbiome transplant from patients with lactation mastitis promotes mastitis in conventional lactating mice.

Introduction: Lactation mastitis seriously severely affects the health of lactating females and their infants, yet the underlying causes of clinical lactation mastitis remain unclear. Methods: In 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. Results: Our 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-1ß, 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. Conclusion: Collectively, our findings demonstrate that the gut microbiota in lactating mastitis patients is dysbiotic and contributes to the pathogenesis of mastitis.

Early Administration of Vancomycin Inhibits Pulmonary Embolism by Remodeling Gut Microbiota.

Pulmonary embolism (PE) is a common and potentially fatal condition in the emergency department, and early identification of modifiable risk factors for prevention and management is highly desirable. Although gut dysbiosis is associated with a high incidence of venous thromboembolism, the role and mechanisms of the gut microbiome in the pathogenesis of venous thromboembolism, especially PE, remain unexplored. Here, we attempted to elucidate the benefits of the gut microbiome in the pathogenesis of PE using multiple antibiotics and fecal microbiota transplantation (FMT) for early intervention in a classical mouse model of PE. The results showed that early administration of various antibiotics (except ampicillin) could inhibit pulmonary thrombosis to a certain extent and reduced mortality in young and old mice with PE. Among them, vancomycin has the best inhibitory effect on PE. With the help of gut microbiota sequencing analysis, we found that antibiotic treatment can reshape the gut microbiota; especially vancomycin can significantly improve the gut microbiota structure in PE mice. Furthermore, FMT could transfer vancomycin-modified gut microbes into mice and inhibit the pathogenesis of PE, possibly due to increased intestinal colonization by Parasutterella. These data elucidate the underlying molecular mechanism by which early administration of vancomycin can remodel the gut microbiota to suppress PE, providing new clues for clinical optimization and development of PE prevention strategies.

Transcranial Doppler analysis based on computer and artificial intelligence for acute cerebrovascular disease.

Cerebrovascular disease refers to damage to brain tissue caused by impaired intracranial blood circulation. It usually presents clinically as an acute nonfatal event and is characterized by high morbidity, disability, and mortality. Transcranial Doppler (TCD) ultrasonography is a non-invasive method for the diagnosis of cerebrovascular disease that uses the Doppler effect to detect the hemodynamic and physiological parameters of the major intracranial basilar arteries. It can provide important hemodynamic information that cannot be measured by other diagnostic imaging techniques for cerebrovascular disease. And the result parameters of TCD ultrasonography such as blood flow velocity and beat index can reflect the type of cerebrovascular disease and serve as a basis to assist physicians in the treatment of cerebrovascular diseases. Artificial intelligence (AI) is a branch of computer science which is used in a wide range of applications in agriculture, communications, medicine, finance, and other fields. In recent years, there are much research devoted to the application of AI to TCD. The review and summary of related technologies is an important work to promote the development of this field, which can provide an intuitive technical summary for future researchers. In this paper, we first review the development, principles, and applications of TCD ultrasonography and other related knowledge, and briefly introduce the development of AI in the field of medicine and emergency medicine. Finally, we summarize in detail the applications and advantages of AI technology in TCD ultrasonography including the establishment of an examination system combining brain computer interface (BCI) and TCD ultrasonography, the classification and noise cancellation of TCD ultrasonography signals using AI algorithms, and the use of intelligent robots to assist physicians in TCD ultrasonography and discuss the prospects for the development of AI in TCD ultrasonography.

The antitumour effects of caloric restriction are mediated by the gut microbiome.

Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γ+CD8+ T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.

Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.

BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied. METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process. RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans.

Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Metabolic fate of black raspberry polyphenols in association with gut microbiota of different origins in vitro.

Polyphenols, ubiquitous in plant-originated foods, exhibit multifarious health benefits but are notorious for their low bioavailability. As the majority of polyphenols enter the colon where they are metabolized into the more bioavailable metabolites with multifarious bioactivities, gut microbiota composition is critical for realizing the health benefits of polyphenols. Black raspberries (BRB) are highly abundant in health-promoting but poorly absorbable polyphenols, primarily ellagitannins and anthocyanins. This study aimed to dissect the bilateral interactions between polyphenols and gut microbiotas of diverse origins. Using an optimized extraction procedure, BRB polyphenols were first comprehensively characterized by UHPLC-QTOF-MS/MS. Next, in vitro anaerobic fermentations with microbiota from human adults, infants, rats, and mice were conducted for comparison of phenolic profile (by metabolomics) and microbiota composition (by 16S rDNA sequencing) before and after fermentation. Bioinformatics analysis further revealed unique polyphenol-microbiota interactions and identified several bacterial species that could potentially produce bioactive and bioavailable phenolic metabolites following BRB consumption.

The crosstalk of intratumor bacteria and the tumor.

The in-depth studies reveal the interaction between the host and commensal microbiomes. Symbiotic bacteria influence in tumor initiation, progression, and response to treatment. Recently, intratumor bacteria have been a burgeoning research field. The tumor microenvironment is under vascular hyperplasia, aerobic glycolysis, hypoxia, and immunosuppression. It might be attractive for bacterial growth and proliferation. As a component of the tumor microenvironment, intratumor bacteria influence tumor growth and metastasis, as well as the efficacy of anti-tumor therapies. Therefore, understanding the intricate interplay of intratumoral bacteria and the host might contribute to better approaches to treat tumors. In this review, we summarize current evidence about roles of intratumor bacteria in tumor initiation and anti-tumor therapy, and what is remained to be solved in this field.

The impact of the microbiome in cancer: Targeting metabolism of cancer cells and host.

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.

Effect of aging on acute pancreatitis through gut microbiota.

Background: Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon. Methods: Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction. Results: The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not. Conclusion: Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.

Crystal structure and Hirshfeld surface analysis of 7,7-dimethyl-2-phenyl-3,3a,4,6,7,8,9,9a-octa-hydro-1H-benzo[f]iso-indole-1,5(2H)-dione.

The title compound, C20H23NO2, was obtained via the reaction of N-allyl-N-phenyl-acryl-amide with 3-iodo-cyclo-hex-2-en-1-one using PdCl2(PPh3)2 as a catalyst. The compound crystallizes in the monoclinic space group P21/c. The fused-ring system is not planar and the five- and six-membered rings are trans-fused. The mol-ecular geometry is partially stabilized by an intra-molecular C-H⋯O hydrogen bond, forming an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯π inter-actions into a three-dimensional network. To further analyse the inter-molecular inter-actions, a Hirshfeld surface analysis was performed. The results indicate that the most important contributions to the overall surface are from H⋯H (65.5%), O⋯H/H⋯O (17.5%) and C⋯H/H⋯C (14.3%) inter-actions.

Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.

BACKGROUND: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis. OBJECTIVE: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response. METHODS: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice. RESULTS: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis. CONCLUSION: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.