Interaction of NF-κB and FOSL1 drives glioma stemness.

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor; GBM's inevitable recurrence suggests that glioblastoma stem cells (GSC) allow these tumors to persist. Our previous work showed that FOSL1, transactivated by the STAT3 gene, functions as a tumorigenic gene in glioma pathogenesis and acts as a diagnostic marker and potential drug target in glioma patients. Accumulating evidence shows that STAT3 and NF-κB cooperate to promote the development and progression of various cancers. The link between STAT3 and NF-κB suggests that NF-κB can also transcriptionally regulate FOSL1 and contribute to gliomagenesis. To investigate downstream molecules of FOSL1, we analyzed the transcriptome after overexpressing FOSL1 in a PDX-L14 line characterized by deficient FOSL1 expression. We then conducted immunohistochemical staining for FOSL1 and NF-κB p65 using rabbit polyclonal anti-FOSL1 and NF-κB p65 in glioma tissue microarrays (TMA) derived from 141 glioma patients and 15 healthy individuals. Next, mutants of the human FOSL1 promoter, featuring mutations in essential binding sites for NF-κB were generated using a Q5 site-directed mutagenesis kit. Subsequently, we examined luciferase activity in glioma cells and compared it to the wild-type FOSL1 promoter. Then, we explored the mutual regulation between NF-κB signaling and FOSL1 by modulating the expression of NF-κB or FOSL1. Subsequently, we assessed the activity of FOSL1 and NF-κB. To understand the role of FOSL1 in cell growth and stemness, we conducted a CCK-8 assay and cell cycle analysis, assessing apoptosis and GSC markers, ALDH1, and CD133 under varying FOSL1 expression conditions. Transcriptome analyses of downstream molecules of FOSL1 show that NF-κB signaling pathway is regulated by FOSL1. NF-κB p65 protein expression correlates to the expression of FOSL1 in glioma patients, and both are associated with glioma grades. NF-κB is a crucial transcription factor activating the FOSL1 promoter in glioma cells. Mutual regulation between NF-κB and FOSL1 contributes to glioma tumorigenesis and stemness through promoting G1/S transition and inhibiting apoptosis. Therefore, the FOSL1 molecular pathway is functionally connected to NF-κB activation, enhances stemness, and is indicative that FOSL1 may potentially be a novel GBM drug target.

Mutations of PsPALM1a and PsPALM1b associated with the afila phenotype in Pea.

Semi-leafless represents an advantageous plant architecture in pea breeding due to its ability to enhance resistance to lodging and potentially to powdery mildew. The introduction of semi-leafless pea varieties is considered a seminal advancement in pea breeding over the past half-century. The afila (af) mutation leads to the replacement of lateral leaflets by highly branched tendrils; combined with the semi-dwarfing le mutation, it forms the semi-leafless cultivated variety. In this study, we identified that mutations in two tandemly-arrayed genes encoding Cys(2)His(2) zinc finger transcription factors, PsPALM1a and PsPALM1b, were closely associated with the afila phenotype. These two genes may be deleted in the af mutant. In situ hybridization showed that both genes exhibit specific expression in early leaflet primordia. Furthermore, suppression of PsPALM1a/PsPALM1b resulted in a high frequency of conversion of lateral leaflets into tendrils. In conclusion, our study provides genetic evidence demonstrating that mutations in PsPALM1a and PsPALM1b are responsible for the af locus, contributing to a better understanding of compound leaf formation in peas and offering new insights for breeding applications related to afila.

Integrated scRNAseq analyses of mouse cochlear supporting cells reveal the involvement of Ezh2 in hair cell regeneration.

BACKGROUND: In lower vertebrates like fish, the inner ear and lateral line hair cells (HCs) can regenerate after being damaged by proliferation/differentiation of supporting cells (SCs). However, the HCs of mouse cochlear could only regenerate within one to two weeks after birth but not for adults. METHODS AND RESULTS: To better understand the molecular foundations, we collected several public single-cell RNA sequencing (scRNAseq) data of mouse cochleae from E14 to P33 and extracted the prosensory and supporting cells specifically. Gene Set Enrichment Analysis (GSEA) results revealed a down-regulation of genes in Notch signaling pathway during postnatal stages (P7 and P33). We also identified 107 time-course co-expression genes correlated with developmental stage and predicated that EZH2 and KLF15 may be the key transcriptional regulators for these genes. Expressions of candidate target genes of EZH2 and KLF15 were also found in supporting cells of the auditory epithelia in chick and the neuromasts in zebrafish. Furthermore, inhibiting EZH2 suppressed regeneration of hair cells in zebrafish neuromasts and altered expressions of some developmental stage correlated genes. CONCLUSIONS: Our results extended the understanding for molecular basis of hair cell regeneration ability and revealed the potential role of Ezh2 in it.

TRPM7 transactivates the FOSL1 gene through STAT3 and enhances glioma stemness.

INTRODUCTION: We previously reported that TRPM7 regulates glioma cells' stemness through STAT3. In addition, we demonstrated that FOSL1 is a response gene for TRPM7, and the FOSL1 gene serves as an oncogene to promote glioma proliferation and invasion. METHODS: In the present study, we determined the effects of FOSL1 on glioma stem cell (GSC) markers CD133 and ALDH1 by flow cytometry, and the maintenance of stem cell activity by extreme limiting dilution assays (ELDA). To further gain insight into the mechanism by which TRPM7 activates transcription of the FOSL1 gene to contribute to glioma stemness, we constructed a FOSL1 promoter and its GAS mutants followed by luciferase reporter assays and ChIP-qPCR in a glioma cell line and glioma patient-derived xenoline. We further examined GSC markers ALDH1 and TRPM7 as well as FOSL1 by immunohistochemistry staining (IHC) in brain tissue microarray (TMA) of glioma patients. RESULTS: We revealed that FOSL1 knockdown reduces the expression of GSC markers CD133 and ALDH1, and FOSL1 is required to maintain stem cell activity in glioma cells. The experiments also showed that mutations of - 328 to - 336 and - 378 to - 386 GAS elements markedly reduced FOSL1 promoter activity. Constitutively active STAT3 increased while dominant-negative STAT3 decreased FOSL1 promoter activity. Furthermore, overexpression of TRPM7 enhanced while silencing of TRPM7 reduced FOSL1 promoter activity. ChIP-qPCR assays revealed that STAT3, present in nuclear lysates of glioma cells stimulated by constitutively activated STAT3, can bind to two GAS elements, respectively. We demonstrated that deacetylation of FOSL1 at the Lys-116 residue located within its DNA binding domain led to an increase in FOSL1 transcriptional activity. We found that the expression of TRPM7, ALDH1, and FOSL1 protein is associated with grades of malignant glioma, and TRPM7 protein expression correlates to the expression of ALDH1 and FOSL1 in glioma patients. CONCLUSIONS: These combined results demonstrated that TRPM7 induced FOSL1 transcriptional activation, which is mediated by the action of STAT3, a mechanism shown to be important in glioma stemness. These results indicated that FOSL1, similar to GSC markers ALDH1 and TRPM7, is a diagnostic marker and potential drug target for glioma patients.

FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.

This review specifically examines the important function of the oncoprotein FOSL1 in the dimeric AP-1 transcription factor, which consists of FOS-related components. FOSL1 is identified as a crucial controller of invasion and metastatic dissemination, making it a potential target for therapeutic treatment in cancer patients. The review offers a thorough examination of the regulatory systems that govern the influence exerted on FOSL1. These include a range of changes that occur throughout the process of transcription and after the translation of proteins. We have discovered that several non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a significant role in regulating FOSL1 expression by directly interacting with its mRNA transcripts. Moreover, an investigation into the functional aspects of FOSL1 reveals its involvement in apoptosis, proliferation, and migration. This work involves a comprehensive analysis of the complex signaling pathways that support these diverse activities. Furthermore, particular importance is given to the function of FOSL1 in coordinating the activation of several cytokines, such as TGF-beta, and the commencement of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that migrate into the tumor microenvironment. There is a specific emphasis on evaluating the predictive consequences linked to FOSL1. Insights are now emerging on the developing roles of FOSL1 in relation to the processes that drive resistance and reliance on specific treatment methods. Targeting FOSL1 has a strong inhibitory effect on the formation and spread of specific types of cancers. Despite extensive endeavors, no drugs targeting AP-1 or FOSL1 for cancer treatment have been approved for clinical use. Hence, it is imperative to implement innovative approaches and conduct additional verifications.

The MIO1-MtKIX8 module regulates the organ size in Medicago truncatula.

Plant organ size is an important agronomic trait tightly related to crop yield. However, the molecular mechanisms underlying organ size regulation remain largely unexplored in legumes. We previously characterized a key regulator F-box protein MINI ORGAN1 (MIO1)/SMALL LEAF AND BUSHY1 (SLB1), which controls plant organ size in the model legume Medicago truncatula. In order to further dissect the molecular mechanism, MIO1 was used as the bait to screen its interacting proteins from a yeast library. Subsequently, a KIX protein, designated MtKIX8, was identified from the candidate list. The interaction between MIO1 and MtKIX8 was confirmed further by Y2H, BiFC, split-luciferase complementation and pull-down assays. Phylogenetic analyses indicated that MtKIX8 is highly homologous to Arabidopsis KIX8, which negatively regulates organ size. Moreover, loss-of-function of MtKIX8 led to enlarged leaves and seeds, while ectopic expression of MtKIX8 in Arabidopsis resulted in decreased cotyledon area and seed weight. Quantitative reverse-transcription PCR and in situ hybridization showed that MtKIX8 is expressed in most developing organs. We also found that MtKIX8 serves as a crucial molecular adaptor, facilitating interactions with BIG SEEDS1 (BS1) and MtTOPLESS (MtTPL) proteins in M. truncatula. Overall, our results suggest that the MIO1-MtKIX8 module plays a significant and conserved role in the regulation of plant organ size. This module could be a good target for molecular breeding in legume crops and forages.

Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy.

OBJECTIVES: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become a common technique in clinical laboratories in recent years. Because most methods are laboratory-developed tests (LDTs), their reproducibility and quality control (QC) have been controversial. In this study, Westgard Sigma Rules were used to evaluate the analytical performance and establish an individualised internal QC (IQC) strategy for these LDTs. METHODS: Taking the LC-MS/MS LDT method for homocysteine (Hcy) as an example, the 'desirable specifications' from the Biological Variation Database were used as quality goals. Based on the external quality assessment (EQA) samples, bias was calculated and the coefficient of variation (CV) was also calculated by IQC measurements for six consecutive months. The analytical performance was evaluated by calculated sigma metrics and an IQC strategy was designed using the Westgard Sigma Rules with run size. RESULTS: Over 116 days within 6 months, a total of 850 data points were collected for each of IQC 1 and IQC 2. The monthly coefficient of variation CV% was 2.57-4.01%, which was non-significant (p-value: 0.75). The absolute bias% for IQC1 and IQC2 was 1.23 and 1.87%, respectively. The allowable total error (TEa) was selected as 15.5%, Sigma metrics were 4.02 and 4.30, and the analytical performance was 'Good'. The 13s/22s/R4s/41s multi rules (n=4, r=1) with a run size of 200 samples were suggested for the Hcy IQC scheme. The quality goal index (QGI) values were over 1.2, indicating that trueness needed to be improved. CONCLUSIONS: The analytical performance of the Hcy LC-MS/MS LDT conformed to the Six Sigma rating level, achieving 'good' (four Sigma). Clinical practice indicated that calibration bias was the primary factor affecting trueness.

A simple and rapid liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 15 bile acids in human serum and its application to patients with decompensated cirrhosis.

Liver cirrhosis is currently the twelfth leading cause of death globally and the sixth leading cause of death in China. Its treatment is expensive. Changes in the composition of the serum bile acid pool are sensitive indicators of the severity of liver cirrhosis. In this study, a novel LC-tandem mass spectrometry (LC-MS/MS) method was developed and used to simultaneously determine 15 bile acids in human serum in patients with decompensated cirrhosis. Sample preparation involved spiking with isotope internal standards followed by protein precipitation. The analytical run time was 5 min. The LC-MS/MS method was fully validated according to Clinical and Laboratory Standards Institute (CLSI) C62A and the consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories. The method achieved an acceptable coefficient of variation for precision (0.83%-14.80%) and accuracy (89.39%-107.62%). Finally, as proof of applicability, the method was applied to patients with decompensated cirrhosis in routine clinical sample analysis. The degree of variation of different bile acids was clearly shown. These results indicated that abnormal metabolic pathways might play important roles in decompensated cirrhosis.

[Work Environment-Mediated Job Burnout and Intention-to-Stay in Registered Nurses].

BACKGROUND: Nurse engagement and retention are critical issues affecting the quality of healthcare. Although the work environment is known to affect nursing performance and patient outcomes, little is known regarding the impact of this environment on nurse burnout and future work intention, especially in non-Western settings. PURPOSE: This study explored the extent to which Taiwanese nurses' perceptions of their practice environment mediates burnout levels and intention-to-stay. METHODS: This descriptive, correlational study, conducted between September and December 2020, recruited nurses employed at a regional teaching hospital located in a relatively rural region in Taiwan. The participants completed standardized questionnaires, including a demographic information form, the 31-item Practice Environment Scale of the Nursing Work Index (PES-NWI), the 22-item Maslach Burnout Inventory (MBI-HSS), and the 6-item Intention-to-stay (ITS) scale. The mediating effect among the variables related to intention-to-stay was examined using Model 4 of the PROCESS macro and tested using the bootstrapping method (repeated 5,000 times) with a p value < .05. RESULTS: The mean age of the 376 participants was 34.3 years (SD = 8.1). Nearly one-third (30.3%) scored > 27 on the emotional exhaustion subscale of the MBI-HSS, indicating they were "highly burned-out". Also, nearly one-third (30.6%) were uncertain about their intention to stay with their current employer. Burnout was associated with intention-to-stay (ß = -.088, p < .001), and holding a positive perception toward their practice environment was shown to mediate the relationship between burnout and intention-to-stay (ß = -.015; p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Targeted interventions and technical support that promote a collaborative climate and psychological empowerment in clinical practice may alleviate burnout and intention-to-leave in nurses and improve workplace quality.

FBXO31 suppresses lipogenesis and tumor progression in glioma by promoting ubiquitination and degradation of CD147.

Glioma is the most frequent tumor occurred in brain and spinal cord with a high mortality and morbidity. This study aimed to explore the effects of FBXO31 on lipid synthesis and tumor progression in glioma. The expression of FBXO31 was low in glioma tissues and cell lines, which indicated poor prognosis in glioma patients. Overexpression of FBXO31 accelerated ubiquitination and degradation of CD147, which downregulated the expression of SREBP1c. In addition, overexpression of FBXO31 resulted in the reduction of lipogenesis through suppressing the activation of AKT/mTOR signaling axis, thus preventing the tumor growth and aggressiveness in glioma. These results provided a new cognition to pathology of glioma and new therapeutic targets for treating glioma in future.

Establishment of reference intervals of homocysteine, cysteine, and methionine in apparently healthy Chinese adults.

BACKGROUND: It has been widely reported that the key biomarkers of homocysteine metabolic pathways have emerged as markers or independent risk factors for cardiovascular disease and many other diseases. To improve the accuracy of evaluation in China, we establish the reference intervals of serum homocysteine (Hcy), cysteine (Cys), and methionine (Met) in apparently healthy Chinese adults. METHODS: We examined 1553 subjects aged ≥20 years who underwent Hcy metabolic pathway tests, in the Chaoyang Central Hospital between January 2019 and December 2020. The serum Hcy, Cys, and Met levels were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to identify sources of variation. A nonparametric method was used to establish the reference intervals. RESULTS: Gender differences were observed in Hcy and Met, with higher levels in males. Reference intervals for males were 6.09-17.00 µmol/L (Hcy) and 19.31-33.68 µmol/L (Met); conversely, the reference intervals for females were 4.61-14.61 µmol/L (Hcy) and 16.16-30.35 µmol/L (Met). The serum Cys reference intervals were seen to be gender-independent, but age-dependent reference intervals were needed; those for Cys were 188.85-334.27 µmol/L, 200.48-340.66 µmol/L, and 216.03-349.67 µmol/L in <40, 40-50, and ≥50 years, respectively. CONCLUSIONS: By this study, the gender- or age-specific reference intervals of Hcy, Cys, and Met that were matched with the Chinese population were established, providing valuable references for clinical work and laboratory researches.

Simultaneous determination of serum homocysteine, cysteine, and methionine in patients with schizophrenia by liquid chromatography-tandem mass spectrometry.

Schizophrenia is a debilitating psychiatric disorder affecting approximately 1% of the population worldwide. Disturbances in the homocysteine metabolism are an important factor in the pathophysiology of schizophrenia. In this research, a novel validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification procedure was developed to investigate three significant compounds of homocysteine metabolism: homocysteine, cysteine, and methionine in patients with schizophrenia and healthy controls. Sample preparation involved a reduction with dithiothreitol followed by protein precipitation, and the chromatographic runtime was 2 min. The LC-MS/MS method was validated according to CLSI C62-A and the Chinese Guidance for Liquid Chromatography and Mass Spectrometry Clinical Application. The performance of the method was excellent with a coefficient of variation for precision in the range of 0.5-6.9%, an accuracy of 90.4-101.6%. In addition, the practical applicability of the method was demonstrated by applying it in the routine sample analysis for a schizophrenic patient. Increased homocysteine levels and decreased cysteine levels were observed in the patient with schizophrenia. These results indicate that the activity of the transsulfuration pathway may play a key role in the pathogenesis of schizophrenia.

Identification of the Wheat (Triticum aestivum) IQD Gene Family and an Expression Analysis of Candidate Genes Associated with Seed Dormancy and Germination

The IQ67 Domain (IQD) gene family plays important roles in plant developmental processes and stress responses. Although IQDs have been characterized in model plants, little is known about their functions in wheat (Triticum aestivum), especially their roles in the regulation of seed dormancy and germination. Here, we identified 73 members of the IQD gene family from the wheat genome and phylogenetically separated them into six major groups. Gene structure and conserved domain analyses suggested that most members of each group had similar structures. A chromosome positional analysis showed that TaIQDs were unevenly located on 18 wheat chromosomes. A synteny analysis indicated that segmental duplications played significant roles in TaIQD expansion, and that the IQD gene family underwent strong purifying selection during evolution. Furthermore, a large number of hormone, light, and abiotic stress response elements were discovered in the promoters of TaIQDs, implying their functional diversity. Microarray data for 50 TaIQDs showed different expression levels in 13 wheat tissues. Transcriptome data and a quantitative real-time PCR analysis of wheat varieties with contrasting seed dormancy and germination phenotypes further revealed that seven genes (TaIQD4/-28/-32/-58/-64/-69/-71) likely participated in seed dormancy and germination through the abscisic acid-signaling pathway. The study results provide valuable information for cloning and a functional investigation of candidate genes controlling wheat seed dormancy and germination; consequently, they increase our understanding of the complex regulatory networks affecting these two traits.

Modulating the Gut Microbiota as a Therapeutic Intervention for Alzheimer's Disease.

Growing evidence suggested that the change of composition and proportion of intestinal microbiota may be related to many diseases, such as irritable bowel syndrome, bipolar disorder, Parkinson's disease, as well as Alzheimer's disease. Current literature supports the fact that unbalanced gut microbial composition (gut dysbiosis) is a risk factor for AD. In our review, we briefly sum up the recent progress regarding the correlations between the gut microbiota and AD. Therapeutic interventions capable of modulating the make-up of the gut microflora may exert beneficial effects on AD, preventing or delaying the beginning of AD or counteracting its development. Additionally, well-documented approaches that can positively influence AD may exert their beneficial effects through modifying the gut microbiota. Therefore, other novel interventions which can target on gut microbiota will also be potential therapies for AD. The chances and challenges that AD is confronted with in the research field of microbiomics are also discussed in this review.

Glycan Assembly Strategy: From Concept to Application.

Glycans have been hot topics in recent years due to their exhibition of numerous biological activities. However, the heterogeneity of their natural source and the complexity of their chemical synthesis impede the progress in their biological research. Thus, the development of glycan assembly strategies to acquire plenty of structurally well-defined glycans is an important issue in carbohydrate chemistry. In this review, the latest advances in glycan assembly strategies from concepts to their applications in carbohydrate synthesis, including chemical and enzymatic/chemo-enzymatic approaches, as well as solution-phase and solid-phase/tag-assisted synthesis, are summarized. Furthermore, the automated glycan assembly techniques are also outlined.

Magnitude and Spatial Distribution Control of the Supercurrent in Bi2O2Se-Based Josephson Junction.

Many proposals for exploring topological quantum computation are based on superconducting quantum devices constructed on materials with strong spin-orbit coupling (SOC). For these devices, full control of both the magnitude and the spatial distribution of the supercurrent is highly demanded, but has been elusive up to now. We constructed a proximity-type Josephson junction on nanoplates of Bi2O2Se, a new emerging semiconductor with strong SOC. Through electrical gating, we show that the supercurrent can be fully turned ON and OFF, and its real-space pathways can be configured either through the bulk or along the edges. Our work demonstrates Bi2O2Se as a promising platform for constructing multifunctional hybrid superconducting devices as well as for searching for topological superconductivity.

Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR-1304 to modulate ERBB4 expression.

Glioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real-time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan-Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit-8 (CCK-8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK-8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR-1304 and circ_0074026 or ERBB4 3'-untranslated region (3'-UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual-luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients' tumor size, WHO grade, disease-free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual-luciferase reporter assay demonstrated that miR-1304 interacted with circ_0074026 and ERBB4 3'-UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR-1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.

TRPM7 channels play a role in high glucose-induced endoplasmic reticulum stress and neuronal cell apoptosis.

High-glucose (HG) levels and hyperglycemia associated with diabetes are known to cause neuronal damage. The detailed molecular mechanisms, however, remain to be elucidated. Here, we investigated the role of transient receptor potential melastatin 7 (TRPM7) channels in HG-mediated endoplasmic reticulum stress (ERS) and injury of NS20Y neuronal cells. The cells were incubated in the absence or presence of HG for 48 h. We found that mRNA and protein levels of TRPM7 and of ERS-associated proteins, such as C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and inducible nitric-oxide synthase (iNOS), increased in HG-treated cells, along with significantly increased TRPM7-associated currents in these cells. Similar results were obtained in cerebral cortical tissue from an insulin-deficiency model of diabetic mice. Moreover, HG treatment of cells activated ERS-associated proapoptotic caspase activity and induced cellular injury. Interestingly, a NOS inhibitor, l-NAME, suppressed the HG-induced increase of TRPM7 expression and cellular injury. siRNA-mediated TRPM7 knockdown or chemical inhibition of TRPM7 activity also suppressed HG-induced ERS and decreased cleaved caspase-12/caspase-3 levels and cell injury. Of note, TRPM7 overexpression increased ERS and cell injury independently of its kinase activity. Taken together, our findings suggest that TRPM7 channel activities play a key role in HG-associated ERS and cytotoxicity through an apoptosis-inducing signaling cascade involving HG, iNOS, TRPM7, ERS proteins, and caspases.

Transcriptomic responses to low temperature stress in the Nile tilapia, Oreochromis niloticus.

The Nile tilapia, Oreochromis niloticus, is a species of high economic value and extensively cultured. The limited stress tolerance of this species to a low temperature usually leads to mass mortality and great loss. Nevertheless, there is limited information on the molecular mechanisms underlying the susceptibility to low temperature in the tilapia. In this study, tilapia was treated at 28 °C to a lethal temperature of 8 °C by a gradual decrement. Transcriptomic response of the immune organ, kidney, in tilapia was characterized using RNA-seq. In total, 2191 genes were annotated for significant expression, which were mainly associated with metabolism and immunity. Pathway analysis showed that immune-related pathways of phagosome and cell adhesion molecules (CAMs) pathway were significantly down-regulated under low temperature. Moreover, ferroptosis, a significantly changed pathway involved in tissue damage and acute renal failure, is reported here for the first time. The levels of serum parameters associated with kidney damage such as urea and uric acid (UA) increased significantly under low temperature. The immunofluorescence staining of the kidney showed that cell apoptosis occurred at low temperature. The results of the present study indicate that exposure to low temperature can cause kidney disfunction and down-regulate the immune-related pathway in the kidney of tilapia. This study provides new insight into the mechanism of kidney damage in fish under low temperature.

Global transcriptome and weighted gene co-expression network analyses reveal hybrid-specific modules and candidate genes related to plant height development in maize.

KEY MESSAGE: Weighted gene co-expression network analysis was explored to find key hub genes involved in plant height regulation. Plant height, an important trait for maize breeding because of its close relatedness to lodging resistance and yield, has been reported to be determined by multiple qualitative and quantitative genes. However, few genes related to plant height have been characterized in maize. Herein, three different maize hybrids, with extremely distinct plant height, which were further classified into low (L), middle (M) and high (H) group, were selected for RNA sequencing at three key developmental stages, namely, jointing stage (I), big flare period (II) and tasseling stage (III). Intriguingly, transcriptome profiles for hybrids ranging from low to high group exhibited significantly similarity in both jointing stage and big flare period. However, remarkably larger differentially expressed genes could be detected between hybrid from low to either middle or high group in tasseling stage. These results were repeatedly observed in both phenotyping and gene ontology enrichment analysis, indicating that transition from big flare period to tasseling stage plays a critical role in determination of plant height. Furthermore, weighted gene co-expression network analysis was explored to find key hub genes involved in plant height regulation. Hundreds of candidate genes, encoding various transcription factors, and regulators involved in internode cell regulation and cell wall synthesis were identified in our network. More importantly, great majority of candidates were correlated to either metabolism or signaling pathway of several plant phytohormones. Particularly, numerous functionally characterized genes in gibberellic acid as well as brassinosteroids signaling transduction pathways were also discovered, suggesting their critical roles in plant height regulation. The present study could provide a modestly comprehensive insight into networks for regulation of plant height in maize.