Commercial utilities and future perspective of nanomedicines
The present review aims to describe the commercial utilities and future perspectives of nanomedicines. Nanomedicines are intended to increase precision medicine and decrease the adverse effects on the patient. Nanomedicines are produced, engineered, and industrialized at the cellular, chemical, and macromolecular levels. This study describes the various aspects of nanomedicine such as governing outlooks over high use of nanomedicine, regulatory advancements for nanomedicines, standards, and guidelines for nanomedicines as per Therapeutic Goods Administration (TGA). This review also focuses on the patents and clinical trials based on nanoformulation, along with nanomedicines utilization as drug therapy and their market value. The present study concludes that nanomedicines are of high importance in biomedical and pharmaceutical production and offer better therapeutic effects especially in the case of drugs that possess low aqueous solubility. The factual data presented in this study will assist the researchers and health care professionals in understanding the applications of nanomedicine for better diagnosis and effective treatment of a disease.
Malviya et al. (2021) Commercial utilities and future perspective of nanomedicines. PeerJ 9:e12392 https://doi.org/10.7717/peerj.12392
Genome-wide identification and expression analysis of ethylene responsive factor family transcription factors in Juglans regia
Background Walnut is an important economic tree species with prominent economic value and ecological functions. However, in recent years, walnuts have become susceptible to drought stress, resulting in a decline in comprehensive benefits. Therefore, it is necessary to identify the regulatory molecular mechanism associated with walnut response to drought. In many plants, ethylene responsive factor (ERF) gene family plays important roles in response to biotic and abiotic stress, especial drought. Therefore, the identification and characterisation of walnut ERF genes will benefit walnut with regard to the clarification of drought response mechanism as well as the management, production, and quality of plantations. Methods ‘ERF’ was compared against the walnut transcriptome, and the JrERFs with a complete open reading frame (ORF) were identified by ORF Finder. The molecular weights, amino acid residues, and theoretical isoelectric point (pI) were predicted by ExPASy. The distribution of JrERFs in chromosome locations was determined based on walnut genome data from NCBI. The intron-exon structures and conserved domains were analysed using Gene Structure Display Server 2.0 and CD-Search, accordingly. Multi-sequence alignment and a phylogenetic tree were constructed by ClustalX2.1 and MEGA7, respectively. The conserved motifs were acquired using MEME. Total RNA was isolated using the cetyltrimethylammonium ammonium bromide (CTAB) method (Yang et al., 2018). Gene expression was determined by using real-time quantitative polymerase chain reaction (qRT-PCR) analysis and calculated according to the 2−ΔΔCT method (Livak & Schmittgen, 2001). Results A total of 44 JrERFs were identified from the walnut transcriptome, whose ORFs were 450–1,239 bp in length. The molecular weights of the JrERF proteins (consisting 149–412 amino acids) were 16.81–43.71 kDa, with pI ranging from 4.8 (JrERF11) to 9.89 (JrERF03). The JrERFs can be divided into six groups (B1–B6), and among the groups, B6 contained the most number of members. Each JrERF contained 1–6 motifs and each motif comprised 9–50 amino acids. Among the motifs, motif1, motif2, and motif3 were the most abundant. More than 40% of JrERFs were up-regulated continuously when subjected to ethephon (ETH), PEG6000, and PEG6000+ETH treatments. Of all the JrERFs, JrERF11 showed the highest expression. Therefore, we conclude that walnut ERF genes are highly conserved and involved in the regulation of drought response in the presence of ETH. JrERFs are possibly important candidate genes for molecular breeding; hence, the findings of this study provides the theoretical basis for further investigation of ERF genes in walnut and other species.
Wang et al. (2021) Genome-wide identification and expression analysis of ethylene responsive factor family transcription factors in Juglans regia. PeerJ 9:e12429 https://doi.org/10.7717/peerj.12429
Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores
Background Colorectal cancer (CRC) is one of the most common malignancies.An early diagnosis and an accurate prognosis are major focuses of CRC research. Tumor microenvironment cells and the extent of infiltrating immune and stromal cells contribute significantly to the tumor prognosis. Methods Immune and stromal scores were calculated based on the ESTIMATE algorithm using the sample expression profile of the The Cancer Genome Atlas (TCGA) database. GSE102479 was used as the validation database. Differentially expressed genes whose expression was significantly associated with the prognosis of CRC patients were identified based on the immune matrix score. Survival analysis was conducted on the union of the differentially expressed genes. A protein–protein interaction (PPI) network was constructed using the STRING database to identify the closely connected modules. To conduct functional enrichment analysis of the relevant genes, GO and KEGG pathway analyses were performed with Cluster Profiler. Pivot analysis of the ncRNAs and TFs was performed by using the RAID2.0 database and TRRUST v2 database. TF-mRNA regulatory relationships were analyzed in the TRRUST V2 database. Hubgene targeting relationships were screened in the TargetScan, miRTarBase and miRDB databases. The SNV data of the hub genes were analyzed by using the R maftools package. A ROC curve was drawn based on the TCGA database. The proportion of immune cells was estimated using CIBERSORT and the LM22 feature matrix. Results The results showed that the matrix score was significantly correlated with colorectal cancer stage T. A total of 789 differentially expressed genes and 121 survival-related prognostic genes were identified. The PPI network showed that 22 core genes were related to the CRC prognosis. Furthermore, four ncRNAs that regulated the core prognosis genes, 11 TFs with regulatory effects on the core prognosis genes, and two drugs, quercetin and pseudoephedrine, that have regulatory effects on colorectal cancer were also identified. Conclusions We obtained a list of tumor microenvironment-related genes for CRC patients. These genes could be useful for determining the prognosis of CRC patients. To confirm the function of these genes, additional experiments are necessary.
Zhu et al. (2021) Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores. PeerJ 9:e12452 https://doi.org/10.7717/peerj.12452
Both landscape heterogeneity and configuration determine Woodlarks (Lullula arborea) breeding territories
Farmland birds have declined in the last decades mostly due to agriculture intensification. The Woodlark Lullula arborea, a farmland species of conservation concern and protected by the European Bird Directive, occurs in a variety of habitats across its geographic range. Although habitat heterogeneity has been recognized as a key feature, the preference or avoidance of particular habitat attributes might differ across its range because different localities may have distinct conditions. Such variation would challenge conservation efforts at the local level. Our aim was to assess habitat associations of Woodlarks and determine whether the habitat attributes identified as important in other locations across its range could be generalised and applied to Austrian populations. In addition, habitat associations can be influenced by land-use change. We examined changes in land use from 2007 to 2016 in 15 municipalities surrounding areas occupied by Woodlarks. We quantified the composition and configuration of the local landscape surrounding 18 singing males’ territories and 16 non-territory sites. We found that the probability of Woodlarks territories increased with landscape heterogeneity between 50% and 70%, increased with dispersed bare soil patches, decreased with overall patch density and were away from dirt roads. Contrary to our expectation, there was no indication of land-use change. In contrast to previous studies, vegetation height, the presence and proximity to woodland were not identified as important habitat characteristics. Thus, some conservation recommendations can be derived from other localities, for example, maintaining or enhancing landscape heterogeneity. However, others should be adapted to local conditions. In Austria, conservation efforts should focus on including dispersed patches of bare soil and limiting the development of dirt roads nearby Woodlark territories, in addition to promoting a heterogeneous landscape.
Resch et al. (2021) Both landscape heterogeneity and configuration determine Woodlarks (Lullula arborea) breeding territories. PeerJ 9:e12476 https://doi.org/10.7717/peerj.12476
Toxicity of clothianidin to common Eastern North American fireflies
Background Previous research suggests that fireflies (Coleoptera: Lampyridae) are susceptible to commonly used insecticides. In the United States, there has been a rapid and widespread adoption of neonicotinoid insecticides, predominantly used as seed coatings on large-acreage crops like corn, soy, and cotton. Neonicotinoid insecticides are persistent in soil yet mobile in water, so they have potential to contaminate firefly habitats both in and adjacent to application sites. As a result, fireflies may be at high risk of exposure to neonicotinoids, possibly jeopardizing this already at-risk group of charismatic insects. Methods To assess the sensitivity of fireflies to neonicotinoids, we exposed larvae of Photuris versicolor complex and Photinus pyralis to multiple levels of clothianidin-treated soil and monitored feeding behavior, protective soil chamber formation, intoxication, and mortality. Results Pt. versicolor and Pn. pyralis larvae exhibited long-term intoxication and mortality at concentrations above 1,000 ng g−1 soil (1 ppm). Under sub-lethal clothianidin exposure, firefly larvae fed less and spent less time in protective soil chambers, two behavioral changes that could decrease larval survival in the wild. Discussion Both firefly species demonstrated sub-lethal responses in the lab to clothianidin exposure at field-realistic concentrations, although Pt. versicolor and Pn. pyralis appeared to tolerate higher clothianidin exposure relative to other soil invertebrates and beetle species. While these two firefly species, which are relatively widespread in North America, appear somewhat tolerant of neonicotinoid exposure in a laboratory setting, further work is needed to extend this conclusion to wild populations, especially in rare or declining taxa.
Pearsons et al. (2021) Toxicity of clothianidin to common Eastern North American fireflies. PeerJ 9:e12495 https://doi.org/10.7717/peerj.12495
Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study
Background Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited. Methods This retrospective study included 167 nucleos(t)ide analogue (NA)-naive patients with CHB. All the patients received TDF at least 12 months before switching and TAF at least 12 months after switching at a single medical center. The Friedman test with Dunn–Bonferroni post hoc tests and repeated-measures analysis of variance was used to analyze the effect of complete viral suppression, alanine aminotransferase (ALT) level normalization, renal function changes, body weight, and body mass index in the periods before and after switching. Results The mean age and TDF treatment duration were 52 ± 11 years and 2.8 years (interquartile range, 1.51–5.15 years), respectively. The complete viral suppression rate was similar between the time of switching and 48 weeks after switching to TAF (77.8% vs 76%, P = 1.000). The percentage of alanine aminotransferase (ALT) normalization increased from 26.3% at TDF start to 81.4% (P < 0.001) at time of switching and 89.2% at 48 weeks after switching to TAF (P = 0.428). The median estimated glomerular filtration rate decreased from 100.09 mL/min/1.73 m² at TDF start to 91.97 mL/min/1.73 m² (P < 0.001) at the time of switching and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73m², P = 1.000). The body weight decreased from 69.2 ± 12.2 kg at TDF start to 67.4 ± 12.1 kg (P < 0.001) at the time of switching to TAF and returned to 68.7 ± 12.7 kg (P < 0.001) 48 weeks thereafter. The body mass index (BMI) decreased from 25 ± 3.3 kg/m² at TDF start to 24.5 ± 3.3 kg/m² (P = 0.002) at the time of switching to TAF and returned to 25.1 ± 3.6 kg/m² (P < 0.001) 48 weeks thereafter. Conclusions Our study showed that switching to TAF from TDF had good antiviral effectiveness and stabilized renal function. The body weight and BMI decreased during TDF therapy and regained after switching to TAF.
Su et al. (2021) Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study. PeerJ 9:e12527 https://doi.org/10.7717/peerj.12527
UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging
Background Osteoporosis has gradually become a public health problem in the world. However, the exact molecular mechanism of osteoporosis still remains unclear. Senescence and osteogenic differentiation inhibition of bone marrow mesenchymal stem cells (BMSCs ) are supposed to play an important part in osteoporosis. Methods We used two gene expression profiles (GSE35956 and GSE35958) associated with osteoporosis and selected the promising gene Ubiquitin-conjugating enzyme E2 E3 (UBE2E3). We then verified its function and mechanism by in vitro experiments. Results UBE2E3 was highly expressed in the bone marrow and positively associated with osteogenesis related genes. Besides, UBE2E3 expression reduced in old BMSCs compared with that in young BMSCs. In in vitro experiments, knockdown of UBE2E3 accelerated cellular senescence and inhibited osteogenic differentiation of young BMSCs. On the other hand, overexpression of UBE2E3 attenuated cellular senescence as well as enhanced osteogenic differentiation of old BMSCs. Mechanistically, UBE2E3 might regulate the nuclear factor erythroid 2-related factor (Nrf2) and control its function, thus affecting the senescence and osteogenic differentiation of BMSCs. Conclusion UBE2E3 may be potentially involved in the pathogenesis of osteoporosis by regulating cellular senescence and osteogenic differentiation of BMSCs.
Liu et al. (2021) UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging. PeerJ 9:e12253 https://doi.org/10.7717/peerj.12253
Misinformation effects in an online sample: results of an experimental study with a five day retention interval
Traditional face-to-face laboratory studies have contributed greatly to our understanding of how misinformation effects develop. However, an area of emerging concern that has been relatively under-researched is the impact of misinformation following exposure to traumatic events that are viewed online. Here we describe a novel method for investigating misinformation effects in an online context. Participants (N = 99) completed the study online. They first watched a 10-min video of a fictional school shooting. Between 5 and 10 days later, they were randomly assigned to receive misinformation or no misinformation about the video before completing a recognition test. Misinformed participants were less accurate at discriminating between misinformation and true statements than control participants. This effect was most strongly supported by ROC analyses (Cohen’s d = 0.59, BF10 = 8.34). Misinformation effects can be established in an online experiment using candid violent viral-style video stimuli.
Sievwright et al. (2021) Misinformation effects in an online sample: results of an experimental study with a five day retention interval. PeerJ 9:e12299 https://doi.org/10.7717/peerj.12299
De novo assembly and functional annotation of blood transcriptome of loggerhead turtle, and in silico characterization of peroxiredoxins and thioredoxins
The aim of this study was to generate and analyze the atlas of the loggerhead turtle blood transcriptome by RNA-seq, as well as identify and characterize thioredoxin (Tnxs) and peroxiredoxin (Prdxs) antioxidant enzymes of the greatest interest in the control of peroxide levels and other biological functions. The transcriptome of loggerhead turtle was sequenced using the Illumina Hiseq 2000 platform and de novo assembly was performed using the Trinity pipeline. The assembly comprised 515,597 contigs with an N50 of 2,631 bp. Contigs were analyzed with CD-Hit obtaining 374,545 unigenes, of which 165,676 had ORFs encoding putative proteins longer than 100 amino acids. A total of 52,147 (31.5%) of these transcripts had significant homology matches in at least one of the five databases used. From the enrichment of GO terms, 180 proteins with antioxidant activity were identified, among these 28 Prdxs and 50 putative Tnxs. The putative proteins of loggerhead turtles encoded by the genes Prdx1, Prdx3, Prdx5, Prdx6, Txn and Txnip were predicted and characterized in silico. When comparing Prdxs and Txns of loggerhead turtle with homologous human proteins, they showed 18 (9%), 52 (18%) 94 (43%), 36 (16%), 35 (33%) and 74 (19%) amino acid mutations respectively. However, they showed high conservation in active sites and structural motifs (98%), with few specific modifications. Of these, Prdx1, Prdx3, Prdx5, Prdx6, Txn and Txnip presented 0, 25, 18, three, six and two deleterious changes. This study provides a high quality blood transcriptome and functional annotation of loggerhead sea turtles.
Hernández-Fernández et al. (2021) De novo assembly and functional annotation of blood transcriptome of loggerhead turtle, and in silico characterization of peroxiredoxins and thioredoxins. PeerJ 9:e12395 https://doi.org/10.7717/peerj.12395
Experimental validation of otolith-based age and growth reconstructions across multiple life stages of a critically endangered estuarine fish
Background The application of otolith-based tools to inform the management and conservation of fishes first requires taxon- and stage-specific validation. The Delta Smelt (Hypomesus transpacificus), a critically endangered estuarine fish that is endemic to the upper San Francisco Estuary (SFE), California, United States, serves as a key indicator species in the SFE; thus, understanding this species’ vital rates and population dynamics is valuable for assessing the overall health of the estuary. Otolith-based tools have been developed and applied across multiple life stages of Delta Smelt to reconstruct age structure, growth, phenology, and migration. However, key methodological assumptions have yet to be validated, thus limiting confidence in otolith-derived metrics that are important for informing major water management decisions in the SFE. Methods Using known-age cultured Delta Smelt and multiple independent otolith analysts, we examined otolith formation, otolith-somatic proportionality, aging accuracy and precision, left-right symmetry, and the effects of image magnification for larval, juvenile, and adult Delta Smelt. Results Overall, otolith size varied linearly with fish size (from 10–60 mm), explaining 99% of the variation in fish length, despite a unique slope for larvae < 10 mm. Otolith-somatic proportionality was similar among wild and cultured specimens. Aging precision among independent analysts was 98% and aging accuracy relative to known ages was 96%, with age estimates exhibiting negligible differences among left and right otoliths. Though error generally increased with age, percent error decreased from 0–30 days-post-hatch, with precision remaining relatively high (≥ 95%) thereafter. Increased magnification (400×) further improved aging accuracy for the oldest, slowest-growing individuals. Together, these results indicate that otolith-based techniques provide reliable age and growth reconstructions for larval, juvenile, and adult Delta Smelt. Such experimental assessments across multiple developmental stages are key steps toward assessing confidence in otolith-derived metrics that are often used to assess the dynamics of wild fish populations.
Xieu et al. (2021) Experimental validation of otolith-based age and growth reconstructions across multiple life stages of a critically endangered estuarine fish. PeerJ 9:e12280 https://doi.org/10.7717/peerj.12280