MicroRNA-224 Expression and Polymorphism Predict the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Liver Resection.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the common lethal types of tumors all over the world. Overexpression of mircoRNA-224 (miR-224) has been reported to act as a potential biomarker for HCC patients. The goal of our study was to assess the prognostic impact of the expression and polymorphism of miR-224 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after liver resection. METHODS: A total of 62 cases of HBV-positive HCC patients, 17 HCC patients without HBV, and 13 healthy cases were enrolled in this study. Blood leukocyte miR-224 level were determined by qRT-PCR. Genotyping analysis of miR-224 rs188519172 was performed using an allele-specific PCR assay. All patients were undergoing partial liver resection and the prognostic values of miR-224 rs188519172 polymorphism for tumor development, survival rate, and liver injury after liver resection were examined. RESULTS: When we compared the blood leukocyte miR-224 level between HCC patients and healthy cases, we found that it was significantly increased in HCC patients. By subgroup analysis, it demonstrated that miR-224 expression was significantly increased in the HBV positive group compared with the HBV negative group. miR-224 rs188519172 AG + GG phenotype was significantly associated with severe liver injury after liver resection and patients carrying miR-224 rs188519172 AG + GG phenotype have a higher risk of cirrhosis and lower overall and disease-free survival rate. Meanwhile, the combination of miR-224 rs188519172 AG + GG phenotype and AFP value could improve the prognosis assessment of HBV related HCC. CONCLUSIONS: miR-224 rs188519172 polymorphism is an indicator of liver injury and a novel prognostic biomarker for tumor development and survival of HBV related HCC patients after liver resection.

A Proactive Intervention Study in Metabolic Syndrome High-Risk Populations Using Phenome-Based Actionable P4 Medicine Strategy.

The integration of predictive, preventive, personalized, and participatory (P4) healthcare advocates proactive intervention, including dietary supplements and lifestyle interventions for chronic disease. Personal profiles include deep phenotypic data and genetic information, which are associated with chronic diseases, can guide proactive intervention. However, little is known about how to design an appropriate intervention mode to precisely intervene with personalized phenome-based data. Here, we report the results of a 3-month study on 350 individuals with metabolic syndrome high-risk that we named the Pioneer 350 Wellness project (P350). We examined: (1) longitudinal (two times) phenotypes covering blood lipids, blood glucose, homocysteine (HCY), and vitamin D3 (VD3), and (2) polymorphism of genes related to folic acid metabolism. Based on personalized data and questionnaires including demographics, diet and exercise habits information, coaches identified 'actionable possibilities', which combined exercise, diet, and dietary supplements. After a 3-month proactive intervention, two-thirds of the phenotypic markers were significantly improved in the P350 cohort. Specifically, we found that dietary supplements and lifestyle interventions have different effects on phenotypic improvement. For example, dietary supplements can result in a rapid recovery of abnormal HCY and VD3 levels, while lifestyle interventions are more suitable for those with high body mass index (BMI), but almost do not help the recovery of HCY. Furthermore, although people who implemented only one of the exercise or diet interventions also benefited, the effect was not as good as the combined exercise and diet interventions. In a subgroup of 226 people, we examined the association between the polymorphism of genes related to folic acid metabolism and the benefits of folate supplementation to restore a normal HCY level. We found people with folic acid metabolism deficiency genes are more likely to benefit from folate supplementation to restore a normal HCY level. Overall, these results suggest: (1) phenome-based data can guide the formulation of more precise and comprehensive interventions, and (2) genetic polymorphism impacts clinical responses to interventions. Notably, we provide a proactive intervention example that is operable in daily life, allowing people with different phenome-based data to design the appropriate intervention protocol including dietary supplements and lifestyle interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00115-z.

Pathogen distribution and infection patterns in pediatric severe pneumonia: A targeted next-generation sequencing study.

OBJECTIVE: Severe pneumonia in children represents a significant clinical challenge due to its high incidence and associated mortality. This study aimed to assess the distribution of pathogens and patterns of infection in pediatric patients with severe pneumonia. METHODS: This study included 110 pediatric patients diagnosed with severe pneumonia, who were admitted to Guangxi Maternal and Child Health Hospital between July 2021 and November 2023. Pathogen-targeted next-generation sequencing (tNGS) was employed to identify respiratory pathogens in these cases. RESULTS: Pathogens were detected in 109 out of 110 cases, yielding a positive detection rate of 99.09%. Among these cases, 25 (22.72%) involved single-pathogen infections, while 84 (76.36%) were characterized by mixed infections. The infection pattern in children with severe pneumonia was relatively common with bacterial-viral coinfection (28.2%, 31/110). A total of 39 pathogens were identified from the 110 children with severe pneumonia, with the top three pathogens being Mycoplasma pneumoniae (30.91%, 34/110), Human Respiratory Syncytial Virus Type A (26.36%, 29/110), and Human Herpesvirus (18.18%, 20/110). Notably, 38.2% (13/34) of the cases were found to have macrolide-resistant Mycoplasma pneumoniae (MRMP). Additionally, 40% (44/110) of the children required admission to the intensive care unit (ICU). CONCLUSION: The application of tNGS demonstrates significant utility in the detection of pathogens in pediatric patients with severe pneumonia. The predominant pathogens identified in this study are Mycoplasma pneumoniae, Human Respiratory Syncytial Virus, and Human Herpesvirus. Furthermore, mixed infections involving multiple pathogens were observed in 76.36% of the cases, and a substantial proportion (40%) of these patients necessitated intensive care.

Synthesis of carboxylate-functionalized graphene nanosheets for high dispersion of platinum nanoparticles based on the reduction of graphene oxide via 1-pyrenecarboxaldehyde.

A one-step reduction/functionalization strategy for the synthesis of carboxylate-functionalized graphene nanosheets is reported in this paper. 1-pyrenecarboxaldehyde (PCA) is introduced as a new reductant for the chemical reduction of graphene oxide (GO), serving three roles: reducing GO to graphene nanosheets (GNs), stabilizing the as-prepared GNs due to the electrostatic repulsion of the oxidation products of PCA (1-pyrenecarboxylate, PC⁻) on the surface of the GNs and anchoring Pt nanoparticles (Pt NPs) with high dispersion and small particle size. Transmission electron microscopy shows that Pt NPs with an average diameter of 1.3 ± 0.2 nm are uniformly dispersed on the surface of the PC⁻-functionalized GNs (PC⁻-GNs). The obtained Pt NPs/PC⁻-GNs nanohybrids have higher electrocatalytic activity and stability towards methanol oxidation in comparison with Pt NPs supported on GNs obtained by the chemical reduction of GO with the typical reductant, hydrazine.

LDAEXC: LncRNA-Disease Associations Prediction with Deep Autoencoder and XGBoost Classifier.

Numerous scientific evidences have revealed that long non-coding RNAs (lncRNAs) are involved in the progression of human complex diseases and biological life activities. Therefore, identifying novel and potential disease-related lncRNAs is helpful to diagnosis, prognosis and therapy of many human complex diseases. Since traditional laboratory experiments are cost and time-consuming, a great quantity of computer algorithms have been proposed for predicting the relationships between lncRNAs and diseases. However, there are still much room for the improvement. In this paper, we introduce an accurate framework named LDAEXC to infer LncRNA-Disease Associations with deep autoencoder and XGBoost Classifier. LDAEXC utilizes different similarity views of lncRNAs and human diseases to construct features for each data sources. Then, the reduced features are obtained by feeding the constructed feature vectors into a deep autoencoder, and at last an XGBoost classifier is leveraged to calculate the latent lncRNA-disease-associated scores using reduced features. The fivefold cross-validation experiments on four datasets showed that LDAEXC reached AUC scores of 0.9676 ± 0.0043, 0.9449 ± 0.022, 0.9375 ± 0.0331 and 0.9556 ± 0.0134, respectively, significantly higher than other advanced similar computer methods. Extensive experiment results and case studies of two complex diseases (colon and breast cancers) further indicated the practicability and excellent prediction performance of LDAEXC in inferring unknown lncRNA-disease associations. TLDAEXC utilizes disease semantic similarity, lncRNA expression similarity, and Gaussian interaction profile kernel similarity of lncRNAs and diseases for feature construction. The constructed features are fed to a deep autoencoder to extract reduced features, and an XGBoost classifier is used to predict the lncRNA-disease associations based on the reduced features. The fivefold and tenfold cross-validation experiments on a benchmark dataset showed that LDAEXC could achieve AUC scores of 0.9676 and 0.9682, respectively, significantly higher than other state-of-the-art similar methods.

Visible-Light Photoredox Catalyzed Double C-H Functionalization: Radical Cascade Cyclization of Ethers with Benzimidazole-Based Cyanamides.

A visible-light photoredox catalyzed radical cascade cyclization of simple ethers with cyanamides is developed at room temperature. This strategy involves sequential inert Csp3-H/Csp2-H functionalizations through intermolecular addition reaction of oxyalkyl radicals to N-cyano groups followed by radical cyclization of iminyl radicals in situ generated with C-2 aryl rings. This method allows for efficient synthesis of tetracyclic benzo[4,5]imidazo[1,2-c]quinazolines. Importantly, this is the first example of an intermolecular-intramolecular radical cascade cyclization reaction of cyanamides.

Linking Short-Chain N-Acyl Homoserine Lactone-Mediated Quorum Sensing and Replant Disease: A Case Study of Rehmannia glutinosa.

Rehmannia glutinosa, a perennial medicinal plant, suffers from severe replant disease under consecutive monoculture. The rhizosphere microbiome is vital for soil suppressiveness to diseases and for plant health. Moreover, N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS) regulates diverse behavior in rhizosphere-inhabiting and plant pathogenic bacteria. The dynamics of short-chain AHL-mediated QS bacteria driven by consecutive monoculture and its relationships with R. glutinosa replant disease were explored in this study. The screening of QS bacteria showed that 65 out of 200 strains (32.5%) randomly selected from newly planted soil of R. glutinosa were detected as QS bacteria, mainly consisting of Pseudomonas spp. (55.4%). By contrast, 34 out of 200 (17%) strains from the diseased replant soil were detected as QS bacteria, mainly consisting of Enterobacteriaceae (73.5%). Functional analysis showed most of the QS bacteria belonging to the Pseudomonas genus showed strong antagonistic activities against Fusarium oxysporum or Aspergillus flavus, two main causal agents of R. glutinosa root rot disease. However, the QS strains dominant in the replant soil caused severe wilt disease in the tissue culture seedlings of R. glutinosa. Microbial growth assays demonstrated a concentration-dependent inhibitory effect on the growth of beneficial QS bacteria (i.e., Pseudomonas brassicacearum) by a phenolic acid mixture identified in the root exudates of R. glutinosa, but the opposite was true for harmful QS bacteria (i.e., Enterobacter spp.). Furthermore, it was found that the population of quorum quenching (QQ) bacteria that could disrupt the beneficial P. brassicacearum SZ50 QS system was significantly higher in the replant soil than in the newly planted soil. Most of these QQ bacteria in the replant soil were detected as Acinetobacter spp. The growth of specific QQ bacteria could be promoted by a phenolic acid mixture at a ratio similar to that found in the R. glutinosa rhizosphere. Moreover, these quorum-quenching bacteria showed strong pathogenicity toward the tissue culture seedlings of R. glutinosa. In conclusion, consecutive monoculture of R. glutinosa contributed to the imbalance between beneficial and harmful short-chain AHL-mediated QS bacteria in the rhizosphere, which was mediated not only by specific root exudates but also by the QQ bacterial community.

Micro-RNA-21 rs1292037 A>G polymorphism can predict hepatocellular carcinoma prognosis (HCC), and plays a key role in cell proliferation and ischemia-reperfusion injury (IRI) in HCC cell model of IRI.

OBJECTIVES: To assess the predictive function of miR-21 rs1292037 A greater than G polymorphism in survival and ischemia-reperfusion injury (IRI) in hepatocellular carcinoma (HCC) patients. METHODS: The experiment was carried out between July 2018 and July 2019, whereas the prospective clinical study was carried out between January 2014 and January 2019. In this study, 62 HCC patients with hepatitis B virus (HBV), 17 HCC patients without HBV, and 13 healthy controls were investigated. Micro-RNA-21 levels in the blood were identified using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and allele specific PCR for miR-21 rs1292037. Partial hepatectomy was performed in all patients, and the tumor development indicators and survival time were evaluated in a subsequent follow-up. Cell-based simulated IRI model of HCC huh7 cell line was used to determine the functions of miR-21 with respect to IRI and proliferation. RESULTS: Micro-RNA-21 levels were significantly increased in HCC patients. Furthermore, an miR- 21 rs1292037 A greater than G polymorphism was found to be significantly associated with HCC prognosis and severity of liver injury after hepatectomy. In vitro study revealed that miR-21 might prevent IRI from occurring, and can induce proliferation in HCC huh7 cells. These functions of miR-21 were demonstrated to be triggered by IL-12A inhibition. CONCLUSION: Micro-RNA-21 rs1292037 A greater than G polymorphism can predict IRI and tumor progression by regulating the miR-21/IL-12A.axis.

[Effects of Rehmannia glutinosa consecutive monoculture on the community structure and diversity of phyllosphere bacteria]. / åœ°é»„è¿žä½œå¯¹å¶é™ ç»†èŒç¾¤è½ç»“æž„åŠå¤šæ ·æ€§çš„å½±å“.

Rehmannia glutinosa, a perennial herbaceous species, belongs to the family Scrophularia-ceae. As a staple medicinal material, its tuberous roots are highly valued in traditional Chinese medicine. However, R. glutinosa suffers from serious consecutive monoculture problems in production, which leads to a decline in both productivity and quality. Phyllosphere bacteria, the most abundant component of phyllosphere microorganisms, play crucial roles in plant growth and health. Characterization of phyllosphere bacteria could provide new insights into the mechanisms of consecutive monoculture problems and their control measures. Meanwhile, the varied taxa could be served as an important indicator of consecutive monoculture problems. The barcoded pyrosequencing of 16S rDNA genes combined with a culture-dependent approach was applied to characterize the shifts of bacterial community structure and diversity in the phyllosphere under consecutive monoculture of R. glutinosa. The results showed that consecutive monoculture clearly affected bacterial community structure in the phyllosphere. The phyllosphere bacterial communities of the two-year monocultured (TY) and the diseased plants (DP) were more similar, and different from the one-year monocultured (OY). The evenness, Shannon and Simpson diversity indices were significantly lower in TY and DP than in OY. Species annotation showed that bacterial community in R. glutinosa phyllosphere mainly consisted of Proteobacteria (91.2%), Firmicutes (5.1%) and Actinobacteria (3.7%). There was no significant difference in the number of detected bacterial taxa. However, Proteobacteria was significantly increased while Firmicutes and Actinobacteria were significantly decreased under consecutive monoculture. At the genus level, the relative abundances of genera Exiguobacterium, Bacillus and Arthrobacter, potentially beneficial microorganisms, were significantly higher in OY than that in TY and DP, but it was opposite for the genus Pseudomonas. The results from the culture-dependent approach and pathogenicity test showed that Pseudomonas plecoglossicida D9, widely isolated from the diseased leaves, was highly pathogenic to leaves. In conclusion, R. glutinosa monoculture resulted in distinct phyllosphere bacterial community variation with the accumulation of pathogen loads at the expense of beneficial microorganisms, which could contribute to the occurrence of leaf disease symptoms,and aggravate R. glutinosa replant disease in a monoculture regime.

The influence of caveolin-1 gene polymorphisms on hepatitis B virus-related hepatocellular carcinoma susceptibility in Chinese Han population: A case-control study.

This study aimed to explore the genetic association of polymorphisms in caveolin-1 gene (CAV1) with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) susceptibility in a Chinese Han population.The genotyping of polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism method. Whether the genotype distribution of polymorphisms in the healthy controls was consistent with Hardy-Weinberg equilibrium (HWE) was detected. The genotype and allele frequency difference between the 2 groups was compared by chi-square test. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to show the relative risk of HCC which resulted from genetic variants in CAV1. Moreover, the linkage disequilibrium of CAV1 polymorphisms was analyzed by Haploview.The AG genotype and A allele of rs1049334 showed significantly higher frequency in HCC patients than that of chronic HBV patients and the healthy controls (P < .05); so their carriage obviously increased the susceptibility to HBV-related HCC, irrespective of the fact whether individuals were infected with hepatitis B virus or not (AG vs GG: OR 1.958, 95% CI 1.050-3.650, OR 1.899, 95% CI 1.034-3.487; A vs G: OR 1.667, 95% CI 1.033-2.689, OR 1.777, 95% CI 1.103-2.863). Additionally, A-G haplotype of rs3807989-rs1049334 showed the protective role for HBV-related HCC (OR 0.102, 95% CI 0.035-0.293; OR 0.135, 95% CI 0.046-0.395).CAV1 rs1049334 polymorphism is significantly associated with the occurrence risk of HBV-related HCC, and the interaction of polymorphisms should not be neglected.