A circular RNA produced by LRBA promotes cirrhotic mouse liver regeneration through facilitating the ubiquitination degradation of p27.

BACKGROUND AND AIMS: Accumulating circular RNAs (circRNAs) play important roles in tissue repair and organ regeneration. However, the biological effects of circRNAs on liver regeneration remain largely unknown. This study aims to systematically elucidate the functions and mechanisms of circRNAs derived from lipopolysaccharide-responsive beige-like anchor protein (LRBA) in regulating liver regeneration. METHODS: CircRNAs derived from mouse LRBA gene were identified using CircBase. In vivo and in vitro experiments were conducted to confirm the effects of circLRBA on liver regeneration. RNA pull-down and RNA immunoprecipitation assays were used to investigate the underlying mechanisms. Clinical samples and cirrhotic mouse models were used to evaluate the clinical significance and transitional value of circLRBA. RESULTS: Eight circRNAs derived from LRBA were registered in CircBase. The circRNA mmu_circ_0018031 (circLRBA) was significantly upregulated in the liver tissues after 2/3 partial hepatectomy (PHx). Adeno-associated virus serotype 8 (AAV8)-mediated knockdown of circLRBA markedly inhibited mouse liver regeneration after 2/3 PHx. In vitro experiments confirmed that circLRBA exerted its growth-promoting function mainly through liver parenchymal cells. Mechanistically, circLRBA acted as a scaffold for the interaction between E3 ubiquitin-protein ligase ring finger protein 123 and p27, facilitating the ubiquitination degradation of p27. Clinically, circLRBA was lowly expressed in cirrhotic liver tissues and negatively correlated with perioperative levels of total bilirubin. Furthermore, overexpression of circLRBA enhanced cirrhotic mouse liver regeneration after 2/3 PHx. CONCLUSIONS: We conclude that circLRBA is a novel growth promoter in liver regeneration and a potential therapeutic target related to deficiency of cirrhotic liver regeneration.

Robust Vehicle Speed Measurement Based on Feature Information Fusion for Vehicle Multi-Characteristic Detection.

A robust vehicle speed measurement system based on feature information fusion for vehicle multi-characteristic detection is proposed in this paper. A vehicle multi-characteristic dataset is constructed. With this dataset, seven CNN-based modern object detection algorithms are trained for vehicle multi-characteristic detection. The FPN-based YOLOv4 is selected as the best vehicle multi-characteristic detection algorithm, which applies feature information fusion of different scales with both rich high-level semantic information and detailed low-level location information. The YOLOv4 algorithm is improved by combing with the attention mechanism, in which the residual module in YOLOv4 is replaced by the ECA channel attention module with cross channel interaction. An improved ECA-YOLOv4 object detection algorithm based on both feature information fusion and cross channel interaction is proposed, which improves the performance of YOLOv4 for vehicle multi-characteristic detection and reduces the model parameter size and FLOPs as well. A multi-characteristic fused speed measurement system based on license plate, logo, and light is designed accordingly. The system performance is verified by experiments. The experimental results show that the speed measurement error rate of the proposed system meets the requirement of the China national standard GB/T 21555-2007 in which the speed measurement error rate should be less than 6%. The proposed system can efficiently enhance the vehicle speed measurement accuracy and effectively improve the vehicle speed measurement robustness.

A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1.

Candida albicans stably colonizes humans but is the leading cause of hospital-acquired fungemia. Traditionally, masking immunogenic moieties has been viewed as a tactic for immune evasion. Here, we demonstrate that C. albicans blocks type I interferon (IFN-I) signaling via translocating an effector protein Cmi1 into host cells. Mechanistically, Cmi1 binds and inhibits TANK-binding kinase 1 (TBK1) to abrogate IFN-regulatory factor 3 (IRF3) phosphorylation, thereby suppressing the IFN-I cascade. Murine infection with a cmi1 mutant displays an exaggerated IFN-I response in both kidneys and bone-marrow-derived macrophages, leading to rapid fungal clearance and host survival. Remarkably, the lack of CMI1 compromises gut commensalism and increases IFN-I response in mouse colonic cells. These phenotypes of cmi1 are rescued by the depletion of IFN-I receptor. This work establishes the importance of TBK1 inhibition in fungal pathogenesis and reveals that a human commensal-pathogenic fungus significantly impacts host immunity during gut colonization and infection via delivering effector proteins into host cells.

An online longitudinal study about search index reflexing public attention of vaccinate against COVID-19.

Background: The coronavirus disease of 2019 (COVID-19) has had catastrophic effects worldwide. Mounting efforts for vaccination against COVID-19 have achieved tremendous progress. Online searching is a voluntary behavior of people might reflect the public attention and awareness.. Screening and analyzing the details of vaccine related searches may help the government to grasp the trend of public opinion and provide a reference for vaccination strategies and future efforts to protect public health. Methods: Three terms related to COVID-19 and COVID-19 vaccine as well as daily relative search volumes (RSV) were retrieved in the Baidu Index (BDI) from 1 January 2020 to 1 July 2021 in China. Besides the national total data, those of the individual provinces/cities/region of Beijing, Shanghai, Guangdong, Heilongjiang, Sichuan, and Tibet were also included. Vaccine-related policies were also gathered during this period. The vaccination rates within China were derived from the National Health Commission of the People's Republic of China, from 23 March 2021 to 1 July 2021. The searching index was calculated by the searching volume and curve graphs were used to demonstrate the variation and the related trend of the RSV and vaccination rates. Results: A total of 548 days' BDI data were retrieved. The national and provincial curves of the BDI exhibited similar fluctuating upward trends, with 5 obvious rises, especially in COVID-19 vaccine searching volume. The vaccination number was correlated with the searching volume growth of COVID-19 vaccine and vaccine uptake (r=0.382, P<0.001; r=0.256, P=0.010). Relevant vaccination events corresponded to the variation searching trend and were attributed to or were influenced by the searching variation. Conclusions: Public awareness about vaccination against COVID-19 was related to the implementation of vaccine policies. Positive vaccine-related policy and high public awareness about vaccination could play a vital role in maximizing the vaccination uptake. Advanced internet data grabbing could consolidate public information in an efficient and timely manner. These findings would support efforts to utilize the big data monitoring of the public opinion to forecast and guide the public health policies. Dynamic monitoring as well as prevention and timely adjustment under this supervision could be expected.

Construction of a predictive nomogram and bioinformatic investigation of the potential mechanism of postoperative early recurrence of hepatocellular carcinoma meeting the Milan criteria.

Background: Hepatectomy is the most common treatment for hepatocellular carcinoma (HCC) meeting the Milan criteria; however, postoperative early recurrence (PER) compromises the survival time. This study aimed to construct a predictive nomogram for PER of HCC patients within the Milan criteria. And the underlying mechanism related to PER may associate with the independent risk factors used to construct the nomogram, therefore, we preliminarily investigated the potential mechanism of PER using The Cancer Genome Atlas (TCGA) database to provide an idea for preventing PER. Methods: Patients with HCC meeting the Milan criteria receiving hepatectomy in our center between 2009 and 2015 were enrolled. The clinical and histological data of all participants were collected. Follow-up was performed at outpatient and PER was defined as recurrence within 2 years after resection. All participants were randomly assigned to the training or validation cohort at a 4:1 ratio. A nomogram was constructed based on the independent risk factors in the training cohort. The accuracy and clinical utility of this nomogram were evaluated using the C-index, calibration plot, and decision curve analysis (DCA). The differentially-expressed genes (DEGs) between early-stage HCC patients with and without PER in TCGA database were identified. Enrichment analysis was performed to determine the potential relapse-related mechanism. Results: The independent risk factors were alpha-fetoprotein (AFP) ≥400 ng/mL, gamma-glutamyl transpeptidase (GGT) ≥60 U/L, Glisson's capsule invasion, microvascular invasion (MVI), and satellite lesions. The C-index value of the nomogram was 0.693 [95% confidence interval (CI): 0.632-0.754; P<0.001] in the training cohort and 0.658 (95% CI: 0.529-0.787; P=0.016) in the validation cohort. The calibration and decision curves demonstrated good accuracy and clinical utility of this nomogram respectively. 133 DEGs were identified and enrichment analysis showed the bile secretion pathway related to PER and two bile secretion pathway-related genes {ATP1A2 [P=0.027; hazard ratio (HR) =2.086, 95% CI: 0.916-4.749] and SLC5A1 (P=0.0016; HR =0.361, 95% CI: 0.145-0.898)} were significantly associated with disease free survival (DFS). Conclusions: Our nomogram has satisfactory accuracy and clinical utility in predicting the PER of patients with HCC meeting the Milan criteria. Aberrant bile secretion may be an important mechanism of PER.

Using search trends before and after the COVID-19 outbreak in China to analyze digestive symptoms: medical informatics study of the Baidu Index data.

Background: From the beginning of 2020, the world was plunged into a pandemic caused by the novel coronavirus disease-19 (COVID-19). People increasingly searched for information related to COVID-19 on internet websites. The Baidu Index is a data sharing platform. The main data provided is the search index (SI), which represents the frequency that keywords are used in searches. Methods: January 9, 2020 is an important date for the outbreak of COVID-19 in China. We compared the changes of SI before and after for 7 keywords, including "fever", "cough", "nausea", "vomiting", "abdominal pain", "diarrhea", "constipation". The slope and peak values of SI change curves are compared. Ten provinces in China were selected for a separate analysis, including Beijing, Gansu, Guangdong, Guangxi, Heilongjiang, Hubei, Sichuan, Shanghai, Xinjiang, Tibet. The change of SI was analyzed separately, and the correlation between SI and demographic and economic data was analyzed. Results: During period I, from January 9 to January 25, 2020, the average daily increase (ADI) of the SI for "diarrhea" was lower than that for "cough" (889.47 vs. 1,799.12, F=11.43, P=0.002). In period II, from January 25 to April 8, 2020, the average daily decrease (ADD) of the SI for "diarrhea" was significantly lower than that for "cough", with statistical significance (cough, 191.40 vs. 441.44, F=68.66, P<0.001). The mean SI after January 9, 2020 (pre-SI) was lower than that before January 9, 2020 (post-SI) (fever, 2,616.41±116.92 vs. 3,724.51±867.81, P<0.001; cough, 3,260.04±308.43 vs. 5,590.66±874.25, P<0.001; diarrhea, 4,128.80±200.82 vs. 4,423.55±1,058.01, P<0.001). The pre-SI mean was correlated with population (P=0.004, R=0.813) and gross domestic product (GDP) (P<0.001, R=0.966). The post-SI peak was correlated with population (P=0.007, R=0.789), GDP (P=0.005, R=0.804), and previously confirmed cases (PCC) (P=0.03, R=0.670). The growth rate of the SI was correlated with the post-SI peak (P=0.04, R=0.649), PCC (P=0.003, R=0.835). Conclusions: Diarrhea was of widespread concern in all provinces before and after the COVID-19 outbreak and may be associated with novel coronavirus infection. Internet big data can reflect the public's concern about diseases, which is of great significance for the study of the epidemiological characteristics of diseases.

Assessment of the digestive system malignancy information in Wikipedia and Baidu Encyclopedia: a longitudinal study.

Background: An increasing number of patients search for medical information on the Internet if they have health problems. The reliability of the online medical information is not yet known. Baidu Encyclopedia and Wikipedia are the most widely used Chinese and English search engines. The quality of the online medical information in these websites needs to be evaluated. We perform this research study to evaluate the quality and timeliness of articles related to digestive system malignancy in articles retrieved from these encyclopedias. A 3-year follow-up was conducted to determine if the quality and timeliness of the articles improved, and comparisons were made between the 2 encyclopedias. Methods: We conducted a search of Wikipedia and Baidu Encyclopedia based on the classification codes of the International Statistical Classification of Diseases and Related Health Problems (10th revision, version 2016), and evaluated the retrieved articles related to digestive system malignancy using the DISCERN instrument. The update timeliness of these websites were evaluated by calculating the update interval of the articles. Results: In 2019 and 2022, we retrieved 50 and 52 articles, respectively, from Baidu Encyclopedia, representing an increase of 2 articles and no deleted articles, and 30 and 31 articles, respectively, from Wikipedia, representing an increase of 1 article and no deleted articles. According to the scores calculated using the DISCERN instrument, in both 2019 and 2022, Wikipedia scored higher than Baidu Encyclopedia in Sections 1 and 2, and the difference was statistically significant. The total score of Wikipedia was higher than that of Baidu Encyclopedia, and the difference was statistically significant. The update interval of Wikipedia was shorter than that of Baidu Encyclopedia with better timeliness and statistical significance. Conclusions: The quality and timeliness of the digestive system malignancy articles on Wikipedia are better than those on Baidu Encyclopedia. The quality of both the Baidu Encyclopedia and Wikipedia articles had improved over the last 3 years. However, there is still no guarantee of the comprehensiveness or reliability of the treatment information obtained from the Internet.

Diabetes mellitus and postoperative blood glucose value help predict posthepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Many complications after hepatectomy can lead to perioperative death, among which posthepatectomy liver failure (PHLF) is the leading one. Existing studies suggest that one of the most important risk factors for PHLF is cirrhosis. Hepatitis B virus (HBV) infection is an important factor in the occurrence of cirrhosis, and the exact relationship between HBV infection and PHLF is not obvious. Diabetes mellitus and postoperative blood glucose are closely associated with liver regeneration, but its exact relationship with PHLF remains unclear. METHODS: We collected clinical indicators from 920 adult patients treated at the Liver Surgery and Transplantation Center of West China Hospital of Sichuan University from April 2009 and April 2019. We conducted a univariate analysis find out the risk factors of PHLF, follow by a multivariate analysis to ascertain the independent risk factors. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficiency of each risk factor. RESULTS: Following hepatectomy, 205 (22.2%) of patients were diagnosed with PHLF. Several variables were confirmed to related with PHLF significantly: diabetes [P<0.01, odds ratio (OR) =10.845, 95% confidence interval (CI): 5.450-21.579], HBV (P<0.01, OR =0.345, 95% CI: 0.187-0.635), blood glucose on the first postoperative day (post-BG1) (P=0.027, OR =1.059, 95% CI: 1.006-1.115), blood glucose on the third postoperative day (post-BG3) (P=0.021, OR =1.085, 95% CI: 1.012-1.162), blood glucose on the fifth postoperative day (post-BG5) (P=0.014, OR =1.119, 95% CI: 1.023-1.225), postoperative total bilirubin (post-TB) (P<0.01, OR =1.160, 95% CI: 1.133-1.187), and liver cirrhosis (P<0.01, OR =0.982, 95% CI: 0.561-1.717) identified to be independent risk factors of PHLF. CONCLUSIONS: Diabetes, HBV, post-BG1, post-BG3, and post-BG5 are related to the development of PHLF, and diabetes and post-BG can be used as predictors of the development of PHLF in patients with hepatocellular carcinoma (HCC).

Comparison of treatments for hepatocellular carcinoma patients with portal vein thrombosis: a systematic review and network meta-analysis.

BACKGROUND: Sorafenib, hepatectomy, and transarterial chemoembolization (TACE) are the recommended treatment for portal vein tumor thrombosis (PVTT) patients. Therefore, the aim of the present study was to conduct a multi-treatment meta-analysis. The aim of the present study was to analyze the survival benefit of different treatments options on PVTT patients. METHODS: We systematically analyzed 12 randomized controlled trials (4,265 participants) from 2012 to 2019, which compared any of the following treatment options on PVTT patients: TACE, sorafenib, hepatectomy, sorafenib + TACE, hepatectomy + TACE, and sorafenib + hepatectomy. The main outcome was the 1-year survival rate of patients. RESULTS: The results of the rank probability of effectiveness showed that sorafenib + TACE was more likely to be the most effective treatment, sorafenib + TACE group was ranged rank 1 when compared with the others [hepatectomy group: odds ratio (OR): 0.79, 95% confidence interval (CI): 0.03-18.26; hepatectomy + TACE group: OR: 0.51, 95% CI: 0.01-13.59; sorafenib group: OR: 0.14, 95% CI 0.01-2.29, sorafenib + hepatectomy group: OR: 0.15, 95% CI: 0.00-24.88; and TACE group: OR: 0.51, 95% CI: 0.02-9.88]. The second most effect treatment option was hepatectomy alone. DISCUSSION: Sorafenib + TACE is more likely to be the most effective treatment option, while hepatectomy alone is the second effective treatment option.

RNA-seq Used to Explore circRNA Expression and Identify Key circRNAs During the DNA Synthesis Phase of Mice Liver Regeneration.

The liver has an excellent capacity for regeneration when faced with external injury and the damage differs from that of other organs in the body. Our aim was to identify the role of circular RNA (circRNA) during the DNA synthesis phase (36 h) of mice liver regeneration. High-throughput RNA sequencing was conducted to explore circRNA and messenger RNA (mRNA) expression in three pairs of mice liver tissue at 0 and 36 h after 2/3 partial hepatectomy. One hundred differentially expressed circRNAs were detected, including 66 upregulated and 34 downregulated circRNAs. We also explored 2483 differentially expressed mRNAs, including 1422 upregulated and 1061 downregulated mRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes indicated that cell cycle regulation, material metabolism, and multiple classical pathways were involved in the DNA synthesis process. A competing endogenous RNA (ceRNA) network containing 5 circRNAs, 28 target genes, and 533 microRNAs (miRNAs) was constructed, and we selected the top 5 miRNAs to map it. Potential key circRNAs were validated with the quantitative real-time PCR technique and their regeneration curves, including consecutive time points, were produced. Finally, a cell counting kit-8 assay on key circRNAs of ceRNA network was performed to further confirm their roles in the DNA synthesis phase of liver regeneration. This study provides a circRNA expression profile for liver regeneration and contributes valuable information for future research.