In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 ...to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes
,
,
, and
genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.
Abstract
With the continuing rise of lipidomic studies, there is an urgent need for a useful and comprehensive tool to facilitate lipidomic data analysis. The most important features making lipids ...different from general metabolites are their various characteristics, including their lipid classes, double bonds, chain lengths, etc. Based on these characteristics, lipid species can be classified into different categories and, more interestingly, exert specific biological functions in a group. In an effort to simplify lipidomic analysis workflows and enhance the exploration of lipid characteristics, we have developed a highly flexible and user-friendly web server called LipidSig. It consists of five sections, namely, Profiling, Differential Expression, Correlation, Network and Machine Learning, and evaluates lipid effects on cellular or disease phenotypes. One of the specialties of LipidSig is the conversion between lipid species and characteristics according to a user-defined characteristics table. This function allows for efficient data mining for both individual lipids and subgroups of characteristics. To expand the server's practical utility, we also provide analyses focusing on fatty acid properties and multiple characteristics. In summary, LipidSig is expected to help users identify significant lipid-related features and to advance the field of lipid biology. The LipidSig webserver is freely available at http://chenglab.cmu.edu.tw/lipidsig
Graphical Abstract
Graphical Abstract
LipidSig is the first web tool dedicated to comprehensive lipidomic data analysis.
In the metazoan S phase, coordinated firing of clusters of origins replicates different parts of the genome in a temporal program. Despite advances, neither the mechanism controlling timing nor that ...coordinating firing of multiple origins is fully understood. Rif1, an evolutionarily conserved inhibitor of DNA replication, recruits protein phosphatase 1 (PP1) and counteracts firing of origins by S-phase kinases. During the midblastula transition (MBT) in
embryos, Rif1 forms subnuclear hubs at each of the large blocks of satellite sequences and delays their replication. Each Rif1 hub disperses abruptly just prior to the replication of the associated satellite sequences. Here, we show that the level of activity of the S-phase kinase, DDK, accelerated this dispersal program, and that the level of Rif1-recruited PP1 retarded it. Further, Rif1-recruited PP1 supported chromatin association of nearby Rif1. This influence of nearby Rif1 can create a "community effect" counteracting kinase-induced dissociation such that an entire hub of Rif1 undergoes switch-like dispersal at characteristic times that shift in response to the balance of Rif1-PP1 and DDK activities. We propose a model in which the spatiotemporal program of late replication in the MBT embryo is controlled by self-stabilizing Rif1-PP1 hubs, whose abrupt dispersal synchronizes firing of associated late origins.
During infections with the malaria parasites
, patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle ...(IEC). In other
species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock Rijo-Ferreira
,
, 746-753 (2020); Smith
.,
, 754-759 (2020), suggesting that intrinsic clock mechanisms may be a fundamental feature of malaria parasites. Moreover, because
cycle times are multiples of 24 h, the IECs may be coordinated with the host circadian clock(s). Such coordination could explain the synchronization of the parasite population in the host and enable alignment of IEC and circadian cycle phases. We utilized an ex vivo culture of whole blood from patients infected with
to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC are correlated across multiple patients, showing that the cycles are phase coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable antimalarial therapies that disrupt this coupling.
•A facile preparation of TA-AuNRs as catalysts was demonstrated.•TA-AuNRs showed excellent catalytic reduction of 4-NP with NaBH4.•Good catalytic activity with kapp of 0.0827 min−1 toward 4-NP.•High ...stability and reusability of TA-AuNRs catalyst.•TA-AuNRs were efficient for the reduction of 4-NP in water samples.
The conversion of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) with sodium borohydride (NaBH4) is the most used chemical reaction for investigating the catalytic activity of various nanomaterials by ultraviolet–visible (UV–Vis) absorption spectroscopy. Herein, a simple approach is reported for the preparation of tannic acid-functionalized gold nanorods (TA-AuNRs), which functioned as catalysts for the reduction of 4-NP with NaBH4. Various processes including UV–Vis absorption spectroscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential, and X-ray photoelectron spectroscopy were employed to characterize the TA-AuNRs. They exhibited good catalytic activity during the conversion of 4-NP. Under optimal conditions, the conversion efficiency was up to 79.04% in 20 min. The reduction reaction followed the pseudo-first-order kinetics, and the rate constant was estimated to be 0.0827 min−1. The active species responsible for the conversion efficiency were investigated through scavenger experiments using 1,4-benzoquinone, isopropyl alcohol (IPA), and ammonia oxalate as scavengers. The conversion efficiency decreased to 35.74% in the presence of IPA, indicating that hydroxyl radicals were the main species that degraded 4-NP. Finally, five recycling steps confirmed the reusability and practical application potential of the TA-AuNRs for the catalytic reduction of water samples spiked with 4-NP.
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Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian ...patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.
Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. ...However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a "pulse" of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APC
. We demonstrate that G1 cyclin-CDKs facilitate the activation and accumulation of TF proteins in S/G2/M phases through inhibiting G1 transcriptional corepressors (Whi5 and Stb1) and APC
, thereby promoting the initiation and propagation of the pulse by the TF network. These findings suggest a unique oscillatory mechanism in which global phase-specific transcription emerges from a pulse-generating network that fires once-and-only-once at the start of the cycle.
•This quadrivalent influenza vaccine was given to subjects 3 to 17 years of age.•Immunogenicity was determined by high seroconversion and seroconversion rates.•This vaccine is well tolerated with a ...favorable safety profile.•A quadrivalent vaccine may overcome the mismatches with influenza B strains.
Quadrivalent influenza vaccines are particularly valuable during seasons in which a mismatch occurs between the predicted influenza B lineage for the trivalent influenza vaccine and the circulating strain. This study evaluated the immunogenicity and safety of a quadrivalent inactivated influenza vaccine AdimFlu-S manufactured in Taiwan for the 2016–2017 influenza season in healthy children.
A total of 174 healthy children aged 3 to 17 years old were separated into 3 groups (Group A: 3–8 years old, vaccine naïve; Group B: 3–8 years old, vaccine non-naïve; Group C: 9–17 years old, any vaccine status). Sera was collected pre and post vaccination for each participant. A hemagglutination inhibition (HAI) assay was utilized to calculate geometric mean titer (GMT), seroprotection rate, and seroconversion rate.
All enrolled participants completed the study. For the four vaccine strains four weeks after the last vaccination, geometric mean titer ratios (GMTRs) were between 2.9 and 20.9, seroconversion rates were between 42.9% and 90.9%, and seroprotection rates were all above 96.4%. This achieved all immunogenicity endpoints and fulfilled the criteria of the European Medical Agency’s Committee for Medicinal Products for Human Use (CHMP). No serious adverse events (AEs) were reported during the follow-up period of 6 months.
This quadrivalent influenza vaccine is demonstrated to be well tolerated and displays robust immunogenicity for each influenza strain. This could potentially improve protection against the antigenically distinct B/Yamagata and B/Victoria lineages.
After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and ...the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy.
S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities.
Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001).
The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.
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