Dr AFC: drug repositioning through anti-fibrosis characteristic.

Fibrosis is a key component in the pathogenic mechanism of a variety of diseases. These diseases involving fibrosis may share common mechanisms and therapeutic targets, and therefore common intervention strategies and medicines may be applicable for these diseases. For this reason, deliberately introducing anti-fibrosis characteristics into predictive modeling may lead to more success in drug repositioning. In this study, anti-fibrosis knowledge base was first built by collecting data from multiple resources. Both structural and biological profiles were then derived from the knowledge base and used for constructing machine learning models including Structural Profile Prediction Model (SPPM) and Biological Profile Prediction Model (BPPM). Three external public data sets were employed for validation purpose and further exploration of potential repositioning drugs in wider chemical space. The resulting SPPM and BPPM models achieve area under the receiver operating characteristic curve (area under the curve) of 0.879 and 0.972 in the training set, and 0.814 and 0.874 in the testing set. Additionally, our results also demonstrate that substantial amount of multi-targeting natural products possess notable anti-fibrosis characteristics and might serve as encouraging candidates in fibrosis treatment and drug repositioning. To leverage our methodology and findings, we developed repositioning prediction platform, drug repositioning based on anti-fibrosis characteristic that is freely accessible via https://www.biosino.org/drafc.

Alterations in bile acid metabolizing gut microbiota and specific bile acid genes as a precision medicine to subclassify NAFLD.

Multiple mechanisms for the gut microbiome contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) have been implicated. Here, we aim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbes in NAFLD by post hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized patients with biopsy-proven NAFLD and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection, and microbial coabundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy [area under the receiver-operator curve (AUC) = 0.97] for detecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-hydroxysteroid dehydrogenase (7α-HSDH), 3α-hydroxysteroid dehydrogenase (baiA), and bile acid-coenzyme A ligase (baiB) was detected in NAFLD. Furthermore, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatus and Eubacterium biforme were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of patients with NAFLD were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

The response of archaeal species to seasonal variables in a subtropical aerated soil: insight into the low abundant methanogens.

Archaea are cosmopolitan in aerated soils around the world. While the dominance of Thaumarchaeota has been reported in most soils, the methanogens are recently found to be ubiquitous but with low abundances in the aerated soil globally. However, the seasonal changes of Archaea community in the aerated soils are still in the mist. In this study, we investigated the change of Archaea in the context of environmental variables over a period of 12 months in a subtropical soil on the Chongming Island, China. The results showed that Nitrososphaera spp. were the dominant archaeal population while the methanogens were in low proportions but highly diverse (including five genera: Methanobacterium, Methanocella, Methanosaeta, Methanosarcina, and Methanomassiliicoccus) in the aerated soil samples determined by high throughput sequencing. A total of 126 LSA correlations were found in the dataset including all the 72 archaeal OTUs and 8 environmental factors. A significance index defined as the pagerank score of each OTU divided by its relative abundance was used to evaluate the significance of each OTU. The results showed that five out of 17 methanogen OTUs were significantly positively correlated with temperature, suggesting those methanogens might increase with temperature rather than being dormant in the aerated soils. Given the metabolic response of methanogens to temperature under aerated soil conditions, their contribution to the global methane cycle warrants evaluation.

Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions.

BACKGROUND: Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM: To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS: The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS: Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION: Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

Identification of microbial markers across populations in early detection of colorectal cancer.

Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-L-glycero-beta-D-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.