Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn, and a mirror site is available at http://bioinfo.org/kobas.

Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.

Background About 70% of children and adolescents worldwide do not meet the recommended level of physical activity (PA), which is closely associated with physical, psychological, and cognitive well-being. Nowadays, the use of technologies to change PA is of interest due to the need for novel, more effective intervention approaches. The previous meta-analyses have examined smartphone-based interventions and their impact on PA in adults, but evidence in children and adolescents still needs further research. Objective This systematic review and meta-analysis aimed to determine the effectiveness of smartphone-based interventions for improving PA in children and adolescents. Methods Five electronic databases (PubMed, Web of Science, OVID, Scopus, and the China National Knowledge Infrastructure) were searched up to June 29, 2020. Randomized controlled trials with a control group that examine the effect of smartphone interventions on PA among children and adolescents were included. Bias risks were assessed using the Cochrane collaboration tool. Meta-analysis was performed to assess the pooled effect on PA using a random effects model. Subgroup analyses were conducted to examine the potential modifying effects of different factors (eg, types of intervention, intervention duration, age, measurement, study quality). Results A total of 9 studies were included in this review, including 4 mobile app interventions, 3 SMS text messaging interventions, and 2 app + SMS text messaging interventions. In general, the risk of bias of included studies was low. Compared with the control group, the use of smartphone intervention significantly improved PA (standardized mean difference [SMD] 0.44, 95% CI 0.11-0.77, P=.009), especially for total PA (TPA; weighted mean difference [WMD] 32.35, 95% CI 10.36-54.33, P=.004) and daily steps (WMD 1185, 95% CI 303-2068, P=.008), but not for moderate-to-vigorous PA (WMD 3.91, 95% CI –1.99 to 9.81, P=.19). High statistical heterogeneity was detected (I2=73.9%, P<.001) for PA. Meta-regression showed that duration (β=–.08, 95% CI –0.15 to –0.01, n=16) was a potential factor for high heterogeneity. The results of subgroup analyses indicated that app intervention (SMD 0.76, 95% CI 0.23-1.30, P=.005), children (SMD 0.64, 95% CI 0.10-1.18, P=.02), “≤8 weeks” (SMD 0.76, 95% CI 0.23-1.30, P=.005), objective measurement (SMD 0.50, 95% CI 0.09-0.91, P=.02), and low risk of bias (SMD 0.96, 95% CI 0.38-1.54, P=.001) can significantly improve PA. Conclusions The evidence of meta-analysis shows that smartphone-based intervention may be a promising strategy to increase TPA and steps in children and adolescents. Currently, app intervention may be a more effective strategy among smartphone intervention technologies. To extend the promise of smartphone intervention, the future needs to design comparative trials among different smartphone technologies. Trial Registration PROSPERO CRD42019148261; https://tinyurl.com/y5modsrd

Background: Elevated histone deacetylase (HDAC) isoenzyme levels have been described in patients with carcinomas and leukemias. HDAC inhibitors (HDACi) have shown promise in the treatment of carcinomas and are currently under intense research. To make better use of HDACi in treating chronic lymphocytic leukemia (CLL), HDAC isoenzyme levels were studied. Methods: Quantitative reverse transcriptase polymerase chain reaction for HDAC isoenzyme was measured in 32 patients with CLL and compared with 17 normal volunteer controls. ZAP-70, CD38 and CD44 were also assayed and correlated to HDAC isoenzyme levels. Results: The results showed: (1) HDAC isoenzyme levels in CLL were significantly increased in class I including HDAC1 and HDAC3, in class II including HADC6, HDAC7, HDAC9 and HDAC10, and in class III including SIRT1 and SIRT6; (2) higher expression of HDAC isoenzyme levels was found in ZAP-70+ compared to ZAP-70– patients, and CD44 expression levels were correlated with HDAC isoenzyme expression levels in the majority of HDAC classes. Conclusions: These results suggest: (1) in CLL, elevated HDAC isoenzyme activity is not restricted to one class, and therefore, HDACi therapy may need to be directed to more than one specific class of HDAC; (2) higher HDAC expression activity may indicate a poor prognosis and more advanced disease stage (through indirect evidence), since higher values were found in patients with ZAP-70+ and higher CD44 expression levels.

More than 100 years ago, German physician Paul Ehrlich first proposed the concept of selectively delivering "magic bullets" to tumors through targeting agents. The targeting therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/ noncleavage linkers, has been extensively studied for decades. The conjugates enable selective delivery of cytotoxic payloads to target cells, which results in improved efficacy, reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD) compared with traditional chemotherapy. PDC and ADC share similar concept, but with vastly different structures and properties. Humanized antibodies introduce high specificity and prolonged half-life, while small molecule weight peptides exhibit higher drug loading and enhanced tissue penetration capacity, and the flexible linear or cyclic peptides are also modified more easily. In this review, the principles of design, synthesis approaches and the latest advances of PDCs are summarized.