Regulatory Mechanisms Research Articles

Tissue adaptation to metabolic stress: insights from SUMOylation

Post-translational modification (PTM) plays a crucial role in adaptation of mammals to environmental changes, enabling them to survive in stressful situations. One such PTM is SUMO modification, which is evolutionarily conserved. It involves the covalent and reversible attachment of a small ubiquitin-like modifier (SUMO) to lysine (Lys) residues in the target protein. SUMOylation regulates various functions, including cell proliferation, differentiation, apoptosis, senescence, and maintenance of specific cellular activities. It achieves this by influencing protein-protein interactions, subcellular localization, protein stability, and DNA binding activity. Mounting evidence suggests that SUMOylation is implicated in the pathogenesis of metabolic disorders such as obesity, insulin resistance, and fatty liver. This review aims to provide an overview of the role of SUMOylation in regulating tissue adaptation to metabolic stress. Recent advancements in spectroscopic techniques have shed light on potential targets of SUMOylation and the underlying regulatory mechanisms have been elucidated, laying the theoretical foundation for the development of targeted SUMOylation interventions for metabolic syndrome while minimizing side effects.

A Novel Anion Receptor Additive for −40 °C Sodium Metal Batteries by Anion/Cation Solvation Engineering

AbstractSodium metal batteries, known for their high theoretical specific capacity, abundant reserves, and promising low‐temperature performance, have garnered significant attention. However, the large ionic radius of Na+ and sluggish transport kinetics across the interfacial structure hinder their practical application. Previous reviews have rarely regulated electrolyte performance from the perspective of anions, as important components of the electrolyte, the regulation mechanism is not well understood. Herein, a novel anion receptor additive, 4‐aminophenylboronic acid pinacol ester (ABAPE), is proposed to weaken the coupling between anions and cations and accelerate Na+ transport kinetics. The results of theoretical calculations and X‐ray photoelectron spectroscopy with deep Ar‐ion etching demonstrate that the introduction of this additive alters the solvation structure of Na+, reduces the desolvation barrier and forms a stable and dense electrode‐electrolyte interface. Moreover, ABAPE forms hydrogen bonds (−NH ⋅ ⋅ ⋅ O/F) with H2O/HF, effectively preventing the hydrolysis of NaPF6 and stabilizing acidic species. Consequently, the Na||Na symmetric cell exhibits excellent long‐cycle performance of 500 h at 1 mA cm−2 and 0.5 mAh cm−2. The Na||Na3V2(PO4)3 (NVP) cell with the addition of ABAPE maintains a capacity retention of 84.29 % at 1 C after 1200 cycles and presents no capacity decay over 150 cycles at −40 °C.

TMIC-21. PYK2/MAPK/ERK SIGNALING PATHWAY REGULATES EXTRACELLULAR VESICLE RELEASE IN GLIOBLASTOMA

Abstract Glioblastoma (GBM), the deadliest brain cancer, typically proves fatal within a year despite treatment. Tumor-associated myeloid cells (TAMs) support GBM growth, treatment resistance, and immune surveillance. Extracellular vesicles (EVs) facilitate communication between tumor and TAMs, exchanging proteins, lipids, RNA, and genetic material. As EVs can travel through the bloodstream to distant tissues, they trigger signaling pathways and metabolic changes in remote organs while also recruiting bone marrow-derived cells and modulating immune responses. Therefore, EVs serve as a crucial mechanism for the distant regulation of the tumor’s immune microenvironment. We hypothesize that Pyk2/MAPK/Erk signaling regulates EV release by modulating the actin cytoskeleton, impacting TAM infiltration and activation in tumors. This study aims to investigate the role of Pyk2/MAPK/Erk in specific EV release in GBM cells, potentially offering insights into therapeutic targets. Using confocal imaging and flow cytometric analysis of EVs, purified from medium conditioned from human primary GBM cell lines with and without Pyk2 CRISPR/Cas9 knock-out (Pyk2KO), the study identified that Pyk2KO cells do not release the population of EVs with diameter bigger then 600nm and up-regulate release of smaller EVs. Additionally, flow cytometric analysis of EVs, released from cells, fluorescently labeled with membrane dye carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), detected 14% of CFSE+ events in EV’s population, purified from Pyk2WT, vs. to 2.5% from Pyk2KO cells. Membrane labeling of cells enables the tracking of microvesicles (MV) shedding and was used to differentiate between MV and ES based on the process of their biogenesis. Considering that larger size and the transition of fluorescence from the plasma membrane are indicative of MVs, our data indicate that Pyk2 is involved in the regulation of MV release. FUNDING: PRSTRT2022 and NIH Grant 1R15CA287203

A Bioconductor/R Workflow for the Detection and Visualization of Differential Chromatin Loops

Background Chromatin loops play a critical role in gene regulation by connecting regulatory loci and gene promoters. The identification of changes in chromatin looping between cell types or biological conditions is an important task for understanding gene regulation; however, the manipulation, statistical analysis, and visualization of data sets describing 3D chromatin structure is challenging due to the large and complex nature of the relevant data sets. Methods Here, we describe a workflow for identifying and visualizing differential chromatin loops from Hi-C data from two biological conditions using the ‘mariner’, ‘DESeq2’ and ‘plotgardener’ Bioconductor/R packages. The workflow assumes that Hi-C data has been processed into ‘.hic’ or ‘.cool’ files and that loops have been identified using an existing loop-calling algorithm. Results First, the ‘mariner’ package is used to merge redundant loop calls and extract interaction frequency counts. Next, ‘DESeq2’ is used to identify loops that exhibit differential contact frequencies between conditions. Finally, ‘plotgardener’ is used to visualize differential loops. Conclusion Chromatin interaction data is an important modality for understanding the mechanisms of transcriptional regulation. The workflow presented here outlines the use of ‘mariner’ as a tool to manipulate, extract, and aggregate chromatin interaction data, ‘DESeq2’ to perform differential analysis of these data across conditions, samples, and replicates, and ‘plotgardener’ to explore and visualize the results.

CNSC-07. OLIGODENDROGLIAL IMPAIRMENT IN WHITE MATTER TRACTS FOLLOWING NEUROFIBROMATOSIS TYPE 1 (NF1) GERMLINE MUTATION OR CARBOPLATIN TREATMENT

Abstract Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome due to mutations in the NF1 gene. The disease affects 1 in 2500-3000 people worldwide and patients are predisposed to neoplasms such as optic pathway glioma, plexiform neurofibroma. In addition, NF1 patients often experience neurological issues such as learning difficulties. Unfortunately, there is no cure for NF1 yet. Chemotherapy (e.g., carboplatin) remains the first-line treatment for NF1-associated low-grade glioma; while effective in reducing tumor burden, it does not reliably restore neuronal function. In this study, we sought to determine how chemotherapy and Nf1 germline mutations influence neurological function, using genetically engineered mice of NF1. Nf1-heterozygous mice received carboplatin (60 mg/kg/day) or vehicle every other day for one week. Their optic nerves were collected and processed for immunofluorescence and transmission electron microscopy (EM). We found that carboplatin treatment reduces the density of oligodendrocytes in Nf1-heterozygous mice and impairs myelination. Moreover, a similar effect of carboplatin was observed in wild-type mice, suggesting that carboplatin impairs oligodendroglia independent of the NF1 status and the effect of carboplatin should also be evaluated in the non-NF1 context. In another set of experiments, we sought to understand how germline Nf1 mutations influences oligodendroglia. Whereas we did not observe a difference in optic nerve oligodendrocyte density in mice with an engineered mutation targeting the GTPase-activating protein-related domain (GRD) domain of the Nf1 gene, a reduction of oligodendrocyte density was observed in mice harboring a patient-derived mutation (R1809C), which localizes outside of the GRD. A similar effect was observed in the corpus callosum of Nf1+/R1809C mice together with myelin impairment, suggesting a RAS-independent mechanism of Nf1 regulation of oligodendrocytes. Together, these findings indicate that both Nf1 germline mutations and chemotherapy could contribute to oligodendrocyte and myelin deficits in white matter tracts.

Targeting splicing for hematological malignancies therapy.

Alterations in splicing patterns of leukemic cells have a functional impact and influence most cellular processes since aberrantly spliced isoforms can provide a proliferative advantage, enable to evade apoptosis, induce metabolic reprogramming, change cell signaling and antitumor immune response, or develop drug resistance. In this Review, we first characterize the general mechanism of mRNA processing regulation with a focus on the role of splicing factors, which are commonly mutated in blood neoplasms. Next, we provide a comprehensive summary on the current understanding of alternative splicing events, which confer resistance to targeted treatment strategies and immunotherapy. We introduce the functional consequences of mis-spliced variants (CD19-∆ex2, CD22-∆ex2, CD22-∆ex5-6, CD33-∆ex2, PIK3CD-S, BCR-ABL35INS, BIM-γ, FPGS-8PR, dCK-∆ex2-3, and SLC29A1-∆ex13) production in leukemic cells. Of therapeutic relevance, we summarize novel strategies focused on pharmacological correction of aberrant splicing, including small-molecule splicing modulators and splice-switching oligonucleotides. We also include the findings of recent preclinical investigation of the antisense strategies based on modified oligonucleotides. Finally, we discuss the potential of emerging combination therapies for the treatment of hematological disorders with disrupted splicing.

METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis.

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-κB pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-α. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-α-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC.

Compromised C3b-VSIG4 axis between decidual NK cells and macrophages contributes to recurrent spontaneous abortion.

NK cells and macrophages constitute the predominant immune cell subsets in the decidua during the first trimester of pregnancy, with macrophages typically adopting an anti-inflammatory phenotype. Conversely, in the third trimester, macrophages undergo a shift towards a pro-inflammatory phenotype concurrent with a reduction in NK cell numbers. The direct regulatory impact of NK cells on macrophage phenotype remains poorly explored. In our investigation, we observed that ICAM1+ macrophages stimulate the expression of intracellular C3 in LFA1+ decidual NK cells. Notably, Cathepsin W within NK cells exhibit the potential to generate active C3b fragments, effectively inhibit the proinflammatory phenotype of macrophages by binding to VSIG4. Our study unveils a direct regulatory mechanism orchestrated by decidual NK cells over macrophages, providing a potential pathogenic explanation for recurrent spontaneous abortion.

CSIG-35. RAB3B DICTATES MTORC1/S6 SIGNALING IN CHORDOMA AND PREDICTS RESPONSE TO MTORC1-TARGETED THERAPY

Abstract Chordoma is a rare mesenchymal malignancy, exhibiting a high tendency to postoperative recurrence and poor prognosis. To date, its tumorigenic regulatory mechanisms remain elusive leading to a lack of effective therapeutic targets and drug sensitivity indicators. Here, via transcriptome and proteome analyses, we unveiled RAB3B as the prominent oncogenic regulator in chordoma. Multidimensional tissue samples further indicated its overexpression and enhancer-associated high transcriptional activity in chordoma. Notably, RAB3B ablation attenuated the chordoma cell growth, stemness, migration and tumorigenicity in vivo and in vitro. Through determining the RAB3B-mediated program in chordoma, we identified that RAB3B was highly associated with PI3K-AKT-mTOR signaling and directly bound to S6. Mechanistically, RAB3B increased the S6K-mediated phosphorylation of S6 by physically interacting with dephosphorylase DUSP12, to block its dephosphorylating of p-S6 specifically at S235/236. Pharmacological targeting mTORC1 pathway via dactolisib and rapamycin dramatically impeded the RAB3B-induced chordoma cell oncogenesis, while RAB3B knockout desensitized mTORC1 inhibition. Clinically, RAB3B/p-S6 suggested a good prognostic value and response to mTORC1 inhibitors for chordoma patients. Altogether, this work uncovers RAB3B as a novel activator of mTORC1 pathway, and suggests the oncogenic and predictive roles of RAB3B/p-S6 in chordoma, indicating therapeutic potentials of mTORC1-targeted therapy in advanced chordoma patients with aberrant RAB3B/p-S6 hyperactivation.

Transcriptome-wide methylated RNA immunoprecipitation sequencing profiling reveals m6A modification involved in response to heat stress in Apostichopus japonicus.

Global warming-induced environmental stresses have diverse effects on gene expression and regulation in the life processes of various aquatic organisms. N6 adenylate methylation (m6A) modifications are known to influence mRNA transcription, localization, translation, stability, splicing, and nuclear export, which are pivotal in mediating stress responses. Apostichopus japonicus is a significant species in aquaculture and a representative of benthic organisms in ecosystems, thus there is a growing need for research on its heat stress mechanism. In this study, m6A-modified whole transcriptome profiles of the respiratory tree tissues of A. japonicus in the control (T18) and high-temperature stress (T32) groups were obtained using MeRIP-seq technology. The results showed that 7,211 common m6A peaks, and 9,459 genes containing common m6A were identified in three replicates T18 and T32 groups. The m6A peaks were found to be highly enriched in the 3' untranslated region, and the common sequence of the m6A peak was also enriched, which was shown as RRACH (R = G or A; H = A, C, or U). A total of 1,200 peaks were identified as significantly differentially enriched in the T32 group compared with the T18 group. Among them, 245 peaks were upregulated and 955 were downregulated, which indicated that high temperature stress significantly altered the methylation pattern of m6A, and there were more demethylation sites in the T32 group. Conjoint analysis of the m6A methylation modification and the transcript expression level (the MeRIP-seq and RNA-seq data) showed co-differentiated 395 genes were identified, which were subsequently divided into four groups with a predominant pattern that more genes with decreased m6A modification and up-regulated expression, including HSP70IV, EIF2AK1, etc. GO enrichment and KEGG analyses of differential m6A peak related genes and co-differentiated genes showed the genes were significantly associated with transcription process and pathways such as protein processing in the endoplasmic reticulum, Wnt signaling pathway, and mTOR signaling pathway, etc. CONCLUSION: The comparisons of m6A modification patterns and conjoint analyses of m6A modification and gene expression profiles suggest that m6A modification was involved in the regulation of heat stress-responsive genes and important functional pathways in A. japonicus in response to high-temperature stress. The study will contribute to elucidate the regulatory mechanism of m6A modification in the response of A. japonicus to environmental stress, as well as the conservation and utilization of sea cucumber resources in the context of environmental changes.

BIOM-35. COMPREHENSIVE IDENTIFICATION OF MRNA ISOFORMS AND THEIR DIAGNOSTIC POTENTIAL IN GLIOMAS

Abstract Most genes generate multiple mRNA isoforms which may differ in their protein-coding capacity. Also, cancer and its prognosis are associated with the altered expression of specific isoforms of a variety of genes as cancer cells can manipulate regulatory mechanisms to express isoforms that provide a survival advantage and/or resistance to therapy. However, the underlying mechanisms behind their pathology are poorly understood. Fifty seven glioma samples that could be categorized unambiguously into Astrocytoma (n=17), Oligodendroglioma (n=16) and Glioblastoma (n=24) based on pathology reports and according to WHO standards were selected for this analysis. Total RNA-Sequencing (RNA-Seq) was performed on RNA isolated from these 57 samples. RNA-Seq data analysis was performed using the DRAGEN RNA application in Illumina BaseSpace and transcript counts were generated after alignment. From these counts, isoforms that were significantly differentially expressed in Astrocytoma (Astro) vs Oligodendroglioma (Oligo), and Astrocytoma vs Glioblastoma (GBM) were identified using the R package, IsoformSwitchAnalyzeR. Approximately 93,000 transcripts were screened in both comparisons of which 4388 and 44 transcript switches were identified as significant at FDR<0.05 in the Astro vs GBM and Astro vs Oligo comparisons, respectively. Applying an additional cut-off based on the difference in isoform fraction or dIF of a transcript between the two groups being compared (dIF>1.0 and dIF<-0.1), the most significant top switches were identified.. Similarly, in the Astro vs GBM comparison, the isoform switch in genes such as MDF1 and RER1 whose overexpression is known to be involved in tumorigenesis and metastasis were among the 155 top switches. Among the six top switches in the Astro vs. Oligo comparison were transcripts of the RENBP and GCNT2 genes which play an important role in the progression of melanoma, gastric and lung cancers. These results indicate that there may be isoform-specific dysregulation within gliomas, and further suggest that their biological significance and diagnostic potential can be explored.

Role of DDR1 in Regulating MMPs in External Root Resorption

Human periodontal ligament cells (hPDLCs) express matrix metalloproteinases (MMPs), a group of enzymes responsible for the destruction of most extracellular matrix proteins in dental tissues, especially MMP-1, MMP-2, and MMP-13. Exploring the regulatory mechanism of MMPs is crucial for understanding external root resorption (ERR), one of the most severe complications, along with substantial loss of dental tissue, induced by trauma, pulpal infection, tooth bleaching, and orthodontic treatment, etc. Discoidin domain receptor 1 (DDR1), a cell surface receptor binding to collagen, has the potential to regulate the expression of MMP-1, MMP-2, and MMP-13, but the mechanism remains unclear. Thus, the present study aimed to investigate the connection and underlying mechanism between MMP-1, MMP-2, MMP-13, and DDR1 in hPDLCs. Our post-replantation ERR model revealed that Mmp-1, Mmp-2, Mmp-13, and Ddr1 all increased in the sites of ERR. hPDLCs with DDR1 knockdown exhibited a substantial reduction in MMP-1, MMP-2, and MMP-13 expression. To further confirm the underlying mechanism, we conducted further in vitro experiments, including RNA sequencing, RNA interference, RT-qPCR, Western blotting, and ELISA. Based on our results, MMP-1 was positively regulated by the Smad2/3 and MEK-ERK1/2 pathways and negatively regulated by the PI3K-Akt pathway through CCN2. MMP-2 and MMP-13 were positively regulated by the Smad2/3 pathway. MMP-13 was positively regulated by the MEK-ERK1/2 and PI3K/Akt signaling pathways. Collectively, DDR1 is a potent regulator of MMP-1, MMP-2, and MMP-13 expression through the Smad2/3, MEK-ERK1/2, and PI3K/Akt signaling pathways. Clarifying the significance and underlying mechanism by which DDR1 is involved in ERR might bring the chances to hinder the pathogenic process of ERR, hence reducing its incidence rate.

Recent advances in the understanding of gonadotrope lineage differentiation in the developing pituitary.

The pituitary gland is a vital endocrine organ regulating body homeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialized endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies. This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment and finally, the mechanisms driving the formation of physical and functional gonadotrope networks. Overall, this review aims to provide new insights into three aspects of the gonadotrope differentiation process by reconsidering pioneering studies in the light of data gained from latest technological developments. Firstly, we re-investigated the long debated developmental trajectory of pituitary gonadotrope cells. Secondly, we reported new regulatory mechanisms of Nr5a1 expression, focusing on the involvement of ERα. Finally, we highlighted the molecular and cellular mechanisms driving gonadotrope network formation during embryogenesis, a process that seems essential for regulation of gonadotrope activity.

PATH-63. M6A REGULATOR-BASED MOLECULAR CLASSIFICATION AND HUB GENES ASSOCIATED WITH IMMUNE INFILTRATION CHARACTERISTICS AND CLINICAL OUTCOMES IN DIFFUSE GLIOMAS

Abstract BACKGROUND m6A methylation modification is a new regulatory mechanism involved in tumorigenesis and tumor-immunity interaction. However, its impact on glioma immune microenvironment and clinical outcome remains unclear. METHODS Comprehensive expression profiles of 18 m6A regulators were used to identify molecular subtypes exhibiting distinct m6A modification patterns in 1673 glioma samples sourced from public datasets. A multi-genes signature was constructed for predicting clinical outcome and response to immunotherapy in glioma patients. Immunohistochemistry and cellular experiments were performed for validation. RESULTS Two m6A subtypes of gliomas were identified. The m6A-low-risk subtype was characterized by paucity of immune infiltrates; Whereas the m6A-high-risk subtype had higher abundances of multiple immune cells including lymphocyte and macrophage as well as increased expression of PD-L1, corresponding to an immunosuppressive phenotype. The m6A-high-risk subtype had poorer survival than the m6A-low-risk subtype in both the glioblastoma and lower grade gliomas cohorts. Eight m6A-related hub genes of high prognostic significances were identified and selected for developing a scoring signature termed as m6Ascore. Elevated m6Ascore indicated worse survival for glioma patients under standard care, but showed enhanced response to immunotherapy. Moreover, we demonstrated that overexpression of FTO, a m6A demethylase, inhibited the expressions of m6A-related hub genes (PTX3, SPAG4), impaired glioma cell viability and reduced macrophage chemotaxis. CONCLUSION This work develops an immune- and clinical-relevant m6A subtyping and a scoring model, which enhances our understanding of the role of m6A modification in regulating immune infiltration microenvironment in gliomas and helps to identify patients who are more likely to benefit from immunotherapy.

Reduced expression of FOXE1 in differentiated thyroid cancer, the contribution of CPG methylation, and their clinical relevance

IntroductionForkhead box E1 (FOXE1) is a transcription factor with a crucial role in thyroid morphogenesis and differentiation. Promoter hypermethylation downregulates FOXE1 expression in different tumor types; nevertheless, its expression and relationship with methylation status in differentiated thyroid cancer (DTC) remain unclear.MethodsA total of 33 pairs of matched samples of PTC tumors and non-tumors were included. Tumor cell cultures were treated with either 5-Aza-2′-deoxycytidine demethylating agent or dimethyl sulfoxide (DMSO). A real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to assess FOXE1 expression. The methylation status was quantified using bisulfite sequencing. A luciferase gene assay was used to determine CpG-island functionality. Gene expression and promoter methylation of FOXE1 and FOXE1-regulated genes were also analyzed with data from The Cancer Genome Atlas (TCGA) thyroid samples.ResultsAfter demethylating treatment, increased FOXE1 mRNA was observed concomitantly with reduced promoter methylation of CpGisland2. A negative correlation between mRNA downregulation and an increased methylation level of CpGisland2 was observed in tumors. Diminished protein expression was also detected in some DTC cell lines and in some tumor samples, suggesting the involvement of post-transcriptional regulatory mechanisms. CPGisland2 was proved to be an enhancer. TCGA data analysis showed low FOXE1 mRNA expression in tumors with a negative correlation with methylation status and a positive correlation with the expression of most of its target genes. Reduced FOXE1 expression, accompanied by a high methylation level, was associated with PTC aggressiveness (tall cell variant, advanced extra thyroid extension, T4 American Joint Committee on Cancer (AJCC) classification), age at diagnosis (over 45 years old), and presence of a BRAFV600E mutation.ConclusionFOXE1 mRNA was downregulated in DTC compared with non-tumors, followed by high CpGisland methylation. A coupling of low mRNA expression and high methylation status was related to characteristics of aggressiveness in DTC tumors.

Electric-Field-Driven Redistribution of Carriers on Catalyst Particles to Improve Photocatalytic Performance.

The photocatalytic performance is primarily determined by carrier separation efficiency. Applying electric fields to enhance carrier separation efficiency and thereby boost catalytic performance has emerged as a promising approach. However, the carrier behavior on catalyst particles under electric fields was still hardly acknowledged. Herein, using single-molecule fluorescence microscopy with high spatiotemporal resolution, the redistribution behavior of carriers on catalyst particles under an electric field was visualized for the first time, which was closely related to the direction and intensity of the electric field. Single-molecule kinetics of the photocatalytic redox reactions induced by carriers have been further obtained, and the results showed that the external electric field had an obvious regulating role in the conversion process and desorption process in this work, which was attributed to the dynamic redistribution of carriers. The improvement of photocatalytic hydrogen evolution reaction (HER) activity further supports the impact of the external electric field on photocatalysis. This work offers new insight into the microscopic regulation mechanism of photocatalytic activity by electric fields and provides new methods for studying the structure-activity relationship in photocatalytic processes.

The Effect of Emotional Coworker Support on Work Engagement Among Pediatric Health Care Providers: The Mediator Role of Emotional Regulation.

Previous findings demonstrated that healthcare workers with a high level of social support are likely to engage in their work. Healthcare workers are not only engaged in the physical problems of their patients but also in their emotional difficulties. Pediatric professionals must express and regulate their own emotions during their interactions with young patients and their families. The purpose of this study was to explore the impact of coworkers' emotional support on healthcare workers' work engagement in pediatric healthcare settings and the emotional regulation mechanisms by which emotional coworker support leads to work engagement. A cross-sectional study was distributed in a Belgian pediatric hospital between October 2021 and December 2021. The sample consisted of 274 healthcare workers who were in direct contact with patients. Participants completed a questionnaire consisting of measures of coworker emotional support, work engagement, emotional suppression, and cognitive reevaluation. Emotional suppression partially mediated the effects of perceived emotional coworker support on work engagement. Coworkers' emotional support fosters work engagement by reducing the negative effects of emotional suppression. Moreover, cognitive evaluation was positively associated with work engagement. These results provide insight into the influence of perceived emotional coworkers, emotional suppression, and cognitive reevaluation on work engagement.

Soil microbial carbon use efficiency and the constraints

Abstract Background Microbial contributions to soil organic carbon formation have received increasing attention, and microbial carbon use efficiency is positively correlated with soil organic carbon storage. Mainbody This work reviews the impact on microbial carbon use efficiency from six constraints, including plant community composition and diversity, soil pH, substrate quality, nutrient availability and stoichiometric ratios, soil texture and aggregates, water and thermal constraints, and external nutrient inputs. In general, the response of microbial carbon use efficiency showed large uncertainty to above constraints, including positive-, negative-, or non-correlation. However, some factors are biased, more likely to promote or inhibit carbon use efficiency. For example, external nutrient input (N, P, K, Ca) tended to promote carbon use efficiency, while climate warming showed more negative influence. Conclusion Further, overwhelming works focused on single constraint, we suggest the importance to consider the synergistic influence of multiple environmental variables on microbial carbon use efficiency, special for the regulation mechanism of biological-environmental interactions.

Prevalence of orthostatic hypotension and associated factors among older people with hypertension in Northern Ethiopia.

The prevalence of hypertension increases with age, and older people with this condition are at increased risk of developing orthostatic hypotension (OH) due to age-related changes in blood pressure regulation mechanisms as well as prescribed medications. OH increases the risk of falls, often with subsequent fractures as well as other morbidity and even mortality. The prevalence and characteristics of OH in older people with hypertension in Low-Income Countries have not been well characterized. This study aims to determine the prevalence of OH and associated factors among older people with hypertension in northern Ethiopia. A hospital-based cross-sectional study was conducted using a convenience sample of patients aged 60 years and older with hypertension receiving pharmacotherapy and followed up at the University of Gondar Hospital, Ethiopia. Blood pressure (BP) was measured in the supine position, and after 3min of standing; the level of BP drop (> 20/10) was used to define measured OH. Data regarding symptoms of OH were also collected using the Orthostatic Hypotension Questionnaire (OHQ). The data were entered into Microsoft Excel version 2016 and exported to SPSS version 20 for statistical analysis. Logistic regression analysis was conducted to assess the factors associated with OH. A total of 240 participants were included, with a mean age of 68.8 ± 7.1 years. The prevalence of OH was 23.8% (CI: 21.5%, 26.1%). Of the medications used, calcium channel blocker (CCBs) treatment was strongly associated with OH (AOR = 2.03[95%CI = 1.08-3.8]). Two-thirds (61.4%) of participants with measured OH experienced relevant symptoms of OH. There was a high prevalence of OH among older patients with hypertension attending a tertiary care hospital in Gondar, with one in four affected. The use of CCBs was identified as an independent risk factor for OH. Most patients with OH experienced relevant symptoms, so monitoring this condition in this group may help prevent adverse consequences.

Genome-Wide Identification and Expression Analysis of the NF-Y Transcription Factor Family in Prunus armeniaca

The nuclear factor Y (NF-Y) gene family plays important roles in regulating many of the biological processes of plants, including oil accumulation. The apricot (Prunus armeniaca) is one of the most commercially traded plants, and apricot kernel oil has a high nutritional value owing to its richness in fatty acids and bioactive compounds. However, the systematic characterization of the PaNF-Y family in the apricot and the underlying regulatory mechanisms involved in oil biosynthesis remain unclear. In this study, a total of 28 PaNF-Y members from the apricot genome were identified and divided into three subfamilies (6 PaNF-YAs, 15 PaNF-YBs, and 7 PaNF-YCs) based on phylogenetic analysis results. The types and distributions of the gene structures and conserved motifs were similar in the clustered PaNF-Ys of the same subfamily. Gene duplication analysis results revealed that segmental duplication events were important for the expansion of the PaNF-Y family. Importantly, transcriptome data analysis results showed that most genes of the PaNF-YA subfamily and PaNF-YB4 of the PaNF-YB subfamily were specifically expressed in the apricot kernel. Furthermore, highly positive correlations were observed between apricot oil content and the transcript levels of PaNF-YA2, PaNF-YA6, and PaNF-YB4. In conclusion, our results provide insights into the molecular mechanisms of the key PaNF-Y genes regulating apricot oil biosynthesis.