Single-cell RNA-seq analysis revealed the stemness of a specific cluster of B cells in acute lymphoblastic leukemia progression
Background Childhood acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The heterogeneous characterization of B cells in ALL progression poses new challenges to researchers. We used single-cell sequencing to explore the critical role of B cells in regulating the ALL immune microenvironment. Method We collected the single cell (sc) RNA-seq data of ALL and health sample from the gene expression omnibus (GEO) database, the “Seurat” and “harmony” R package was used for quality control and scRNA-seq analysis, in which the CellMarker2.0 database was used for cell type annotation. Subsequently, the FindAllMarkers function was used to identify the differentially expressed genes (DEGs) among various cell types and the DAVID database was applied for the biological process of DEGs. Then, the “inferCNV” package was used for copy number variation, regulons and cell communication were performed by SCENIC tool and CellChat package. The role of the target gene in regulating ALL progression was assessed using RT-qPCR, Transwell and scratch healing assays. Results We identified nine mainly cell clusters after scRNA-seq analysis, in which the B cells had higher infiltration proportion in the ALL samples and were sub-clustered into five cell sub-groups. The B cells 1 is closely associated with cell proliferation and stemness (TNFAIP3 and KDM5B), and the significant CNV of amplification occurred on chr6 and chr21 that supported stemness of B cells1. RXRB is a key transcription factor mediated the proliferation of B cells 1, which in turn suppressed hematopoietic stem cells (HSCs) proliferation and promoted cytotoxic NK/T cells activation through diverse cell communication ways. One of the key regulators of B cells is MYC, which promotes the migration and invasive ability of cell line leukemia cell lines. Conclusion This study reveals the stemness characteristics of B cells and their critical role in ALL progression, a finding that provides new potential directions for the development of targeted therapies against ALL.
Wang et al. (2024) Single-cell RNA-seq analysis revealed the stemness of a specific cluster of B cells in acute lymphoblastic leukemia progression. PeerJ 12:e18296 https://doi.org/10.7717/peerj.18296
Assessing acute effects of two motor-cognitive training modalities on cognitive functions, postural control, and gait stability in older adults: a randomized crossover study
Background The process of aging often accompanies a decline in cognitive function, postural control, and gait stability, consequently increasing the susceptibility to falls among older individuals. In response to these challenges, motor-cognitive training has emerged as a potential intervention to mitigate age-related declines. Objective This study aims to assess the acute effects of two distinct motor-cognitive training modalities, treadmill dual-task training (TMDT) and interactive motor-cognitive training (IMCT), on cognitive function, postural control, walking ability, and dual-task performance in the elderly population. Method In this randomized crossover study, 35 healthy elderly individuals (aged 60–75) participated in three acute training sessions involving TMDT, IMCT, and a control reading condition. Assessments of executive function, postural control, gait performance, and cognitive accuracy were conducted both before and after each session. Results Both TMDT and IMCT improved executive functions. Notably, IMCT resulted in a significant enhancement in correct response rates and a reduction in reaction times in the Stroop task (p < 0.05) compared to TMDT and the control condition. IMCT also led to an increase in dual-task gait speed (p < 0.001) and showed a trend towards improved cognitive accuracy (p = 0.07). Conversely, TMDT increased postural sway with eyes open (p = 0.013), indicating a potential detriment to postural control. Conclusion The findings suggest that IMCT holds greater immediate efficacy in enhancing cognitive function and gait stability among older adults compared to TMDT, with a lesser adverse impact on postural control. This underscores the potential of IMCT as a preferred approach for mitigating fall risk and enhancing both cognitive and physical functions in the elderly population.
Li et al. (2024) Assessing acute effects of two motor-cognitive training modalities on cognitive functions, postural control, and gait stability in older adults: a randomized crossover study. PeerJ 12:e18306 https://doi.org/10.7717/peerj.18306
Indigo alleviates psoriasis through the AhR/NF-κB signaling pathway: an in vitro and in vivo study
Background Psoriasis is a chronic inflammatory skin disease. A strong association between the AhR/ NFκB axis and the inflammatory response in psoriasis. Indigo (IDG) has demonstrated significant anti-inflammatory properties. This study aimed to assess the anti-psoriatic efficacy of IDG while investigating the underlying mechanisms involved. Methods In the in vitro experiments, cell viability was assessed using the CCK-8. qRT-PCR was employed to measure the mRNA levels of NF-κB, TNF-α, IL-1β, AhR, and CYP1A1. Western blotting was conducted to examine alterations in cytoplasmic and nuclear AhR protein levels. Additionally, an IDG nanoemulsion (NE) cream was prepared for the in vivo experiments. A psoriasis-like skin lesion mice model was induced using IMQ (62.5 mg/day for 7 days). The severity of psoriasis was evaluated using PASI, and skin lesions were scored while epidermal thickness was assessed via HE staining. The expression of inflammatory markers, including IL-6, IL-13, IL-17A, MCP-1, and TNF-α, was detected in skin lesions using Luminex. The levels of CYP1A1, p65, and p-p65 proteins were determined by Western blotting. Results LPS stimulation significantly elevated TNF-α, IL-6, and NF-κB mRNA levels, which were notably reduced by IDG treatment. Additionally, IDG significantly enhanced the expression of AhR and CYP1A1 mRNA. Further investigation revealed that IDG facilitated AhR translocation from the cytoplasm to the nucleus. In the IMQ-induced psoriasis-like mouse model, IDG NE substantially ameliorated the severity of skin lesions. Moreover, IDG NE treatment reduced the upregulation of inflammatory cytokines such as IL-6, IL-17A, MCP-1, and TNF-α in IMQ-induced skin lesions. It was also observed that IDG NE treatment increased CYP1A1 protein expression while inhibiting p65 and p-p65 protein expression. Conclusion IDG emerges as a promising treatment for psoriasis, demonstrating effective therapeutic outcomes. Its mechanism of action is likely linked to the modulation of the AhR/NFκB signaling pathway.
Lin et al. (2024) Indigo alleviates psoriasis through the AhR/NF-κB signaling pathway: an in vitro and in vivo study. PeerJ 12:e18326 https://doi.org/10.7717/peerj.18326
Sequence characteristics, expression and subcellular localization of PtCYP721A57 gene from cytochrome P450 family in Polygala tenuifolia willd
The Cytochrome P450 (CYP450) family is the largest enzyme protein family in plants, distributed across various organs and involved in significant catalytic activities in primary and secondary metabolic processes. In this study, we cloned the PtCYP721A57 gene, characterized its open reading frame (ORF), and conducted comprehensive analyses including physicochemical properties, evolutionary relationships, subcellular localization, prokaryotic expression, and correlation between the relative expression of different parts and the content of tenuifolin, hormones, and abiotic stress response associated with the encoded protein. The ORF of PtCYP721A57 was 1,521 bp, with a secondary structure predominantly composed of α-helices and random coils. Subcellular localization experiments confirmed the presence of PtCYP721A57 in the endoplasmic reticulum. For prokaryotic expression, we constructed the recombinant plasmid pET28a-PtCYP721A57 using pET28a as the vector, which was then transformed into BL21(DE3). Induction with Isopropyl β-D-1-thiogalactopyranoside (IPTG) at temperatures of 16 and 25 °C and varying concentrations (0.1, 0.2, 0.5, 1, 2 mM) resulted in the formation of inclusion bodies, with higher expression observed at 25 °C. Our qPCR analyses revealed that PtCYP721A57 exhibited the highest expression in the cortex of Polygala tenuifolia, followed by roots and xylem, correlating with the observed tenuifolin content distribution. Induction with abscisic acid (ABA) and chitosan (CHT) initially decreased PtCYP721A57 expression followed by a subsequent increase, peaking at 48 h. Similarly, drought stress induced a gradual increase in PtCYP721A57 expression, also peaking at 48 h. NaCl treatment for 6 h significantly upregulated PtCYP721A57 expression. In conclusion, our study provides foundational insights into the PtCYP721A57 gene in Polygala tenuifolia, laying the groundwork for further exploration of its role in the biosynthesis pathway of triterpenoid saponins.
Luo et al. (2024) Sequence characteristics, expression and subcellular localization of PtCYP721A57 gene from cytochrome P450 family in Polygala tenuifolia willd. PeerJ 12:e18089 https://doi.org/10.7717/peerj.18089
Biodiversity assessment and environmental risk analysis of the single line transgenic pod borer resistant cowpea
Background The discussion surrounding biological diversity has reached a critical point with the introduction of Nigeria’s first transgenic food crop, the pod borer-resistant (PBR) cowpea. Questions have been raised about the potential risks of the transgenic Maruca vitrata-resistant cowpea to human health and beneficial insects. Public apprehension, coupled with social activists’ calling for the removal of this crop from the nation’s food market, persists. However, there is a lack of data to counter the assertion that cultivating PBR cowpea may have adverse effects on biodiversity and the overall ecological system. This research, with its multifaceted objective of examining the environmental safety of PBR cowpea and assessing its impact on biodiversity compared to its non-transgenic counterpart, IT97KN, is of utmost importance in providing the necessary data to address these concerns. Methods Seeds for both the transgenic PBR cowpea and its isoline were obtained from the Institute for Agricultural Research (IAR) Zaria before planting at various farm sites (Addae et al., 2020). Throughout the experiment, local cultural practices were strictly followed to cultivate both transgenic and non-transgenic cowpeas. Elaborate taxonomic keys were used to identify arthropods and other non-targeted organisms. Principal component analysis (PCA) was used to evaluate potential modifications in all ecological niches of the crops. The lmer function of the R package lme4 was used to analyze diversity indices, including Shannon, Pielou, and Simpson. The Bray–Curtis index was used to analyzed potential modifications in the dissimilarities of non-targeted organisms’ communities. Results Examination of ecological species abundance per counting week (CW) revealed no disruption in the biological properties of non-targeted species due to the cultivation of transgenic PBR cowpea. Analysis of species evenness and diversity indices indicated no significant difference between the fields of transgenic PBR cowpea and its isoline. Principal component analysis results demonstrated that planting PBR cowpea did not create an imbalance in the distribution of ecological species. All species and families observed during this study were more abundant in transgenic PBR cowpea fields than in non-transgenic cowpea fields, suggesting that the transformation of cowpea does not negatively impact non-targeted organisms and their communities. Evolution dynamics of the species community between transgenic and non-transgenic cowpea fields showed a similar trend throughout the study period, with no significant divergence induced in the community structure because of PBR cowpea planting. This study concludes that planting transgenic PBR cowpea positively influences biodiversity and the environment.
Isah et al. (2024) Biodiversity assessment and environmental risk analysis of the single line transgenic pod borer resistant cowpea. PeerJ 12:e18094 https://doi.org/10.7717/peerj.18094
The impact of combined application of biochar and fertilizer on the biochemical properties of soil in soybean fields
Background Heilongjiang Province is a major soybean production area in China. To improve soil structure and increase soybean yield, this study examined the effects of combined biochar and chemical fertilizer application on the biochemical properties of soil in a maize-soybean rotation system. Methods The research were conducted from 2021 to 2022 at Heshan Farm Science Park in Heilongjiang Province, this field plot experiment utilized two soybean varieties, Heihe 43 (a high-protein variety) and Keshan 1 (a high-oil variety). In 2021, two plots with similar fertility levels were selected for planting soybeans and maize. In 2022, a maize-soybean rotation was implemented with five treatments: conventional fertilization (CK), increased biochar+reduced fertilizer 1 (F1+B), reduced fertilizer 1 (F1), increased biochar+reduced fertilizer 2 (F2+B), and reduced fertilizer 2 (F2). The study systematically analyzed the effects of combined biochar and chemical fertilizer application on soil chemical properties and microbial characteristics. Results Over 2 years, results showed that combined application effectively improved soil chemical traits. Compared to conventional fertilization (CK) and reduced fertilization (F1, F2), t he combined application of biochar and chemical fertilizer (F1+B, F2+B) increased soil pH, EC and the absolute value of zeta potential of soil surface, the CEC of soil significantly increased by 15.6–44.3%, the soil surface charge density and the soil surface charge quantity significantly increased by 16.4–73.5%. The combined application of biochar and chemical fertilizer also effectively enhanced the abundance and diversity of soil microbes. Dominant bacterial groups in soybean field soils under different treatments included Actinobacteria, Acidobacteria, Chloroflexi, and Proteobacteria; while dominant fungal groups were Ascomycota, Basidiomycota, and Mortierellomycota. Alpha and Beta diversity analyses revealed that the F1+B treatment significantly enhanced the species richness and diversity of bacteria and fungi in the soil, increasing the proportion and evenness of dominant and beneficial genera.
Zhang et al. (2024) The impact of combined application of biochar and fertilizer on the biochemical properties of soil in soybean fields. PeerJ 12:e18172 https://doi.org/10.7717/peerj.18172
Bioconversion of mango peels into itaconic acid through submerged fermentation and statistical optimization of parameters through response surface methodology
Itaconic acid is an industrially crucial organic acid due to its broad range of applications. The main hurdle in itaconic acid production is the high cost of the substrate, i.e., pure glucose, required for the fermentation process. Pakistan annually produces about 1.7 to 1.8 million metric tonnes of mango fruit. Keeping this in view, the potential of a sugar-rich fruit by-product, i.e., mango peels, was analyzed to be used as a substrate for the biosynthesis of itaconic acid using Aspergillus niger by submerged fermentation. Different physicochemical parameters (incubation period, temperature, agitation rate, inoculum size, and pH) were optimized using the central composite design (CCD) design of response surface methodology (RSM). The maximum production of itaconic acid, i.e., 4.6 g/L, was analyzed using 10% mango peels w/v (water hydrolysate), 3 mL inoculum volume after 5 days of fermentation period at pH 3, and a temperature of 32 °C when the media was kept at a 200-rpm agitation speed. The itaconic acid extraction from mango peels was done using the solvent extraction method using n-butanol. The identification and quantification of itaconic acid produced in the study were done using the Fourier Transform Infrared Spectroscopy (FTIR) spectrum and the High-Performance Liquid Chromatography (HPLC) method. According to HPLC analysis, 98.74% purity of itaconic acid was obtained in the research. Hence, it is concluded from the results that sugar-rich mango peels can act as a promising substrate for the biosynthesis of itaconic acid. Further conditions can be optimized at the bioreactor level to meet industrial requirements.
Saeed et al. (2024) Bioconversion of mango peels into itaconic acid through submerged fermentation and statistical optimization of parameters through response surface methodology. PeerJ 12:e18188 https://doi.org/10.7717/peerj.18188
ALKBH5 modulation of ferroptosis in recurrent miscarriage: implications in cytotrophoblast dysfunction
Background As one of the most common and abundant internal modifications of eukaryotic mRNA, N6-methyladenosine (m6A) modifications are closely related to placental development. Ferroptosis is a newly discovered form of programmed cell death. During placental development, placental trophoblasts are susceptible to ferroptosis. However, the interactions of m6A and ferroptosis in trophoblast physiology and injury are unclear. Methods Recurrent miscarriage (RM) was selected as the main gestational disease in this study. Published data (GSE76862) were used to analyze the gene expression profiles in patients with RM. The extent of m6A modification in total RNA of villous tissues between patients with RM and healthy controls (HC) was compared. ALKBH5 (encoding AlkB homolog 5, RNA demethylase) was selected as the candidate gene for further research. Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry (IHC) confirmed the elevated expression of ALKBH5 in the cytotrophoblasts of patients with RM. Then, cell counting kit-8 assays, glutathione disulfide/glutathione quantification, 2′,7′-dichlorfluorescein-diacetate staining, and malonaldehyde assays were used to explore the alterations of ferroptosis-related characteristics following RAS-selective lethal (RSL3) stimulation after overexpression of ALKBH5. Thereafter, we re-analyzed the published RNA sequencing data upon knockdown of ALKBH5, combined with published tissue RNA-seq data, and FTL (encoding ferritin light chain) was identified as the ferroptosis-related gene in cytotrophoblasts of patients with RM that is regulated by ALKBH5. Finally, western blotting and IHC confirmed the increased expression of FTL in the cytotrophoblasts from patients with RM. Results Total m6A levels were decreased in patients with RM. The most significant differentially m6A-related gene was ALKBH5, which was increased in patients with RM. In vitro cell experiments showed that treatment with RSL3 resulted in increased cell death and upregulated ALKBH5 expression. Overexpression of ALKBH5 alleviated RSL3-induced HTR8 cell death and caused decreased levels of intracellular oxidation products. Published transcriptome sequencing revealed that FTL was the major ferroptosis-related gene regulated by ALKBH5 in the villous tissues of patients with RM. Consistent with the expression of ALKBH5, FTL was increased by RSL3-induction and increased in patients with RM. Conclusion Elevated ALKBH5 alleviated RSL3-induced cytotrophoblast cell death by promoting the expression of FTL in patients with RM. Our results supported the view that ALKBH5 is an important regulator of the ferroptosis-related etiology of RM and suggested that ALKBH5 could be responsible for epigenetic aberrations in RM pathogenesis.
Qin et al. (2024) ALKBH5 modulation of ferroptosis in recurrent miscarriage: implications in cytotrophoblast dysfunction. PeerJ 12:e18227 https://doi.org/10.7717/peerj.18227
Predicting the influence of extreme temperatures on grain production in the Middle-Lower Yangtze Plains using a spatially-aware deep learning model
Grain crops are vulnerable to anthropogenic climate change and extreme temperature events. Despite this, previous studies have often neglected the impact of the spatio-temporal distribution of extreme temperature events on regional grain outputs. This research focuses on the Middle-Lower Yangtze Plains and aims to address this gap as well as to provide a renewed projection of climate-induced grain production variability for the rest of the century. The proposed model performs significantly superior to the benchmark multilinear grain production model. By 2100, grain production in the MLYP is projected to decrease by over 100 tons for the low-radiative-forcing/sustainable development scenario (SSP126) and the medium-radiative-forcing scenario (SSP245), and about 270 tons for the high-radiative-forcing/fossil-fueled development scenario (SSP585). Grain production may experience less decline than previously projected by studies using Representative Concentration Pathways. This difference is likely due to a decrease in coldwave frequency, which can offset the effects of more frequent heatwaves on grain production, combined with alterations in supply-side policies. Notably, the frequency of encoded heatwaves and coldwaves has a stronger impact on grain production compared to precipitation and labor indicators; higher levels of projected heatwaves frequency correspond with increased output variability over time. This study emphasizes the need for developing crop-specific mitigation/adaptation strategies against heat and cold stress amidst global warming.
Mu et al. (2024) Predicting the influence of extreme temperatures on grain production in the Middle-Lower Yangtze Plains using a spatially-aware deep learning model. PeerJ 12:e18234 https://doi.org/10.7717/peerj.18234
Exploring the scale effect of nonpoint source pollution risk on water quality in Lake Basins of Central Yunnan Plateau using the Minimum Cumulative Resistance model
Nonpoint source (NPS) pollution has emerged as the predominant water environment issue confronting plateau lakes in central Yunnan. Quantitative analysis of the impact of NPS pollution on water quality constitutes the key to preventing and controlling water pollution. However, currently, there is a dearth of research on identifying NPS pollution risks and exploring their relationship with water quality based on the Minimum Cumulative Resistance (MCR) model in the plateau lake basins of central Yunnan. Particularly, studies on the spatial heterogeneity of the impact of NPS pollution on water quality from a multi-scale perspective are scarce. Therefore, this study focuses on three typical lake basins in the Central Yunnan Plateau–Fuxian Lake, Xingyun Lake, and Qilu Lake (the Three Lakes). Utilizing the MCR model to identify NPS pollution risks, the study analyzes seven different scales, including sub-basins, riparian buffer zones (100 m, 300 m, 500 m, 700 m, and 1,000 m) and lakeshore zones, to reveal the multi-scale effects of NPS pollution on water quality through correlation analysis. The results indicate that: (1) Over 60% of the areas in the Three Lakes Basin are at high or extremely high risk, mainly concentrated in flat terrain and around inflow rivers; (2) The area of NPS pollution from paddy field source landscape (PFSL) is greater than that from construction land source landscape (CLSL), and the high-risk areas of NPS pollution are also larger for PFSL compared to CLSL; (3) The mean resistance values of PFSL and CLSL show a significant negative correlation with monthly mean values of water quality indexes (NH3-N, TP, CODCr), with the 1,000 m riparian buffer zone scale showing the greatest correlation with most water quality indexes, especially NH3-N; (4) The correlation between the mean resistance value of CLSL and the monthly mean values of water quality indexes is significantly higher than that of PFSL, indicating a greater impact of CLSL on water quality compared to PFSL. In summary, PFSL and CLSL are the primary sources of NPS pollution in the Three Lakes Basins. The 1,000 m riparian buffer zone scale is the most sensitive to the impact of NPS pollution on water quality. This study provides scientific references for landscape pattern optimization and precise control of NPS pollution risks in the Central Yunnan Plateau lake basins and offers a new research perspective for exploring multi-scale effects of NPS pollution on water quality.
Environmental Contamination and Remediation
Spatial and Geographic Information Science
Fu et al. (2024) Exploring the scale effect of nonpoint source pollution risk on water quality in Lake Basins of Central Yunnan Plateau using the Minimum Cumulative Resistance model. PeerJ 12:e18247 https://doi.org/10.7717/peerj.18247