Pan-cancer investigation of RFX family and associated genes identifies RFX8 as a therapeutic target in leukemia.

Background: Several transcription factors and co-factors are encoded by the RFX (Regulatory Factor X) family (RFX1-8) and associated genes (RFXAP and RFXANK). Increasing evidence suggests that the RFX family and associated genes are involved in the development and progression of cancer. However, no prior research has focused on a multi-omic analysis of these genes to evaluate their role in tumor progression. Methods: Using combined TCGA and GTEx pan-cancer data, we investigated the expression patterns and survival profiles of these ten genes. We then focused on RFX8 to analyze its clinicopathological and therapeutic features. Finally, we conducted experimental validation of RFX8 function in acute myeloid leukemia (AML). Results: RFX5 and RFXANK showed higher expression levels, while RFX6 showed lower expression levels in most types of cancer, with RFX8 being the most upregulated in LAML. RFX2 and RFXAP demonstrated prognostic significance in eight types of cancer, and RFX8 showed significance in six types of cancer. The expression of these ten genes exhibited specific characteristics in immune subtypes, tumor microenvironment, and stemness. The expression of RFX8 was correlated with various tumor stages, microsatellite instability (MSI), tumor mutation burden (TMB), immune cell infiltration, and immune-checkpoint expression. Additionally, RFX8 was found to regulate tumorigenesis and sensitivity to chelerythrine in AML. Conclusions: Our work delineated the landscape of the RFX family and associated genes in the pan-cancer context and the specific role of RFX8 in AML. These findings might offer cues for further investigations of these genes in cancer biology.

Unveiling kiwifruit TCP genes: evolution, functions, and expression insights.

The TEOSINTE-BRANCHED1/CYCLOIDEA/PROLEFERATING-CELL-FACTORS (TCP) gene family is a plant-specific transcriptional factor family involved in leaf morphogenesis and senescence, lateral branching, hormone crosstalk, and stress responses. To date, a systematic study on the identification and characterization of the TCP gene family in kiwifruit has not been reported. Additionally, the function of kiwifruit TCPs in regulating kiwifruit responses to the ethylene treatment and bacterial canker disease pathogen (Pseudomonas syringae pv. actinidiae, Psa) has not been investigated. Here, we identified 40 and 26 TCP genes in Actinidia chinensis (Ac) and A. eriantha (Ae) genomes, respectively. The synteny analysis of AcTCPs illustrated that whole-genome duplication accounted for the expansion of the TCP family in Ac. Phylogenetic, conserved domain, and selection pressure analysis indicated that TCP family genes in Ac and Ae had undergone different evolutionary patterns after whole-genome duplication (WGD) events, causing differences in TCP gene number and distribution. Our results also suggested that protein structure and cis-element architecture in promoter regions of TCP genes have driven the function divergence of duplicated gene pairs. Three and four AcTCP genes significantly affected kiwifruit responses to the ethylene treatment and Psa invasion, respectively. Our results provided insight into general characters, evolutionary patterns, and functional diversity of kiwifruit TCPs.

Rbm46 inhibits reactive oxygen species in mouse embryonic stem cells through modulating BNIP3-mediated mitophagy.

Embryonic stem cells (ESCs) exhibit a metabolic preference for glycolysis over oxidative phosphorylation to meet their substantial adenosine triphosphate (ATP) demands during self-renewal. This metabolic choice inherently maintains low mitochondrial activity and minimal reactive oxygen species (ROS) generation. Nonetheless, the intricate molecular mechanisms governing the restraint of ROS production and the mitigation of cellular damage remain incompletely elucidated. In this study, we reveal the pivotal role of RNA-binding motif protein 46 (RBM46) in ESCs, acting as a direct post transcriptional regulator of ROS levels by modulating BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) mRNA expression. Rbm46 knockout lead to diminished mitochondrial autophagy, culminating in elevated ROS within ESCs, disrupting the delicate balance required for healthy self-renewal. These findings provide insights into a novel mechanism governing ROS regulation in ESCs.

Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1.

Although tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML), TKI resistance remains a major challenge. Here, we demonstrated that plant homeodomain finger protein 8 (PHF8), a histone demethylase was aberrantly enriched in CML samples compared to healthy controls. PHF8 inhibited CML cell differentiation and promoted CML cell proliferation. Furthermore, the proliferation-inhibited function of PHF8-knockdown have stronger effect on imatinib mesylate (IM)-resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Overall, our study suggests that targeting PHF8, which directly regulates BCR::ABL1 expression, is a useful therapeutic approach for CML.

Health risk study of cadmium, chromium, lead and arsenic in reservoir water of Changzhou, China.

Accurately assessing the health risks of human exposure to heavy metals via water is of great importance for performing targeted health risk prevention measures. To better understand the concentration characteristics and potential harm to human health of cadmium, chromium, lead and arsenic in the main drinking water-type reservoirs of Changzhou city, we collected samples from the Haidi Reservoir, Dongjin Reservoir, Xinfushan Reservoir, Maodong Reservoir and Xiangyang Reservoir of Changzhou in the summer of 2019. The results showed that the daily average comprehensive exposure level of metals was much lower than the provisional tolerated daily intake (PTDI), i.e., Cd: 1 µg kg-1 d-1; Cr: 3 µg kg-1 d-1; Pb: 3.57 µg kg-1 d-1; and As: 2.14 µg kg-1 d-1. The comprehensive non-carcinogenic risk levels of four metals under water-drinking exposure and water-skin exposure routes ranged from 4.68E - 3 to 1.69E - 1, and the carcinogenic risk ranged from 2.09E - 5 to 7.30E - 5, which were all at acceptable risk levels. Although lead and chromium were present at acceptable health risk levels, they still represented the main pollutants of potential health risk in the local water environment from a non-carcinogenic or carcinogenic perspective, and they should be listed as the primary targets for water environmental risk management.

ß-Catenin-treated peptides effectively inhibit the proliferation of colorectal cancer.

To verify the inhibitory mechanism of ß-catenin-designed peptides in colorectal cancer(CRC) tumors, the following experiments were performed. In vitro colony formation, Transwell assays, and flow cytometry were performed to assess the biological effects of designed peptides (F18KD, F20A4-7k, F20A4-10k, and F20A3-9k + F20A4-10k + F20A5-9k) in HT-29 cells. In vivo xenograft experiments were performed and treated with peptides. Next, tumors were subjected to Hematoxylin and eosin staining (HE), immunohistochemical, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays to evaluate the inhibitory effect of peptides on tumors. ß-Catenin levels were quantified via western blotting (WB) and quantitative real-time polymerase chain reaction, and ß-catenin was located using confocal laser scanning microscopy. T-cell factor-4 (TCF-4), C-myc, and CCND1 levels were quantified via WB. Results were obtained as following. First, the peptides reduced viability, migration, and invasion; promoted apoptosis; and stabilized the S phase of HT-29 cells. Second, peptides suppressed tumor growth and downregulated the expression of CD34, vascular endothelial growth factor, and ß-catenin in tumors. Furthermore, we found that peptides downregulated ß-catenin expression in both the cytoplasm and nucleus; TCF-4, C-myc, and CCND1 expression was also downregulated. Notably, ß-catenin-targeting peptides had a better inhibitory effect on CRC than non-ß-catenin-target peptides, and a combination of peptides exerted a more potent inhibitory effect on CRC than single peptides. It suggested that ß-Catenin-targeting peptides promote apoptosis in CRC tumors by inhibiting activation of the Wnt/ß-catenin pathway.

Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling.

The blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), which remains a major challenge in clinical management. However, the underlying molecular mechanism driving blastic transformation remains unclear. Here, we show that ASF1A, an essential activator, enhanced the transformation to CML-BC by mediating cell differentiation arrest. ASF1A expression was aberrantly increased in bone marrow samples from CML-BC patients compared with newly diagnosed CML-chronic phase (CP) patients. ASF1A inhibited cell differentiation and promoted CML development in vivo. Mechanistically, we identified ASF1A as a coactivator of the Notch transcriptional complex that induces H3K56ac modification in the promoter regions of Notch target genes, and subsequently enhanced RBPJ binding to these promoter regions, thereby enhancing Notch signaling activation to mediate differentiation arrest in CML cells. Thus, our work suggests that targeting ASF1A might represent a promising therapeutic approach and a biomarker to detect disease progression in CML patients.

Comprehensive Analysis of a Ferroptosis Pattern and Associated Prognostic Signature in Acute Myeloid Leukemia.

Ferroptosis is a widespread form of programmed cell death. The environment of cancer cells makes them vulnerable to ferroptosis, including AML cells, yet the specific association between ferroptosis and AML outcome is little known. In this study, we utilized ferroptosis-related genes to distinguish two subtypes in TCGA cohort, which were subsequently validated in independent AML cohorts. The subtypes were linked with tumor-related immunological abnormalities, mutation landscape and pathway dysregulation, and clinical outcome. Further, we developed a 13-gene prognostic model for AML from DEG analysis in the two subtypes. A risk score was calculated for each patient, and then the overall group was stratified into high- and low-risk groups; the higher risk score correlated with short survival. The model was validated in both independent AML cohorts and pan-cancer cohorts, which demonstrated robustness and extended the usage of the model. A nomogram was constructed that integrated risk score, FLT3-ITD, TP53, and RUNX1 mutations, and age. This model had the additional value of discriminating the sensitivity of several chemotherapeutic drugs and ferroptosis inducers in the two risk groups, which increased the translational value of this model as a potential tool in clinical management. Through integrated analysis of ferroptosis pattern and its related model, our work shed new light on the relationship between ferroptosis and AML, which may facilitate clinical application and therapeutics.

Phosphorylated viral protein evades plant immunity through interfering the function of RNA-binding protein.

Successful pathogen infection in plant depends on a proper interaction between the invading pathogen and its host. Post-translational modification (PTM) plays critical role(s) in plant-pathogen interaction. However, how PTM of viral protein regulates plant immunity remains poorly understood. Here, we found that S162 and S165 of Chinese wheat mosaic virus (CWMV) cysteine-rich protein (CRP) are phosphorylated by SAPK7 and play key roles in CWMV infection. Furthermore, the phosphorylation-mimic mutant of CRP (CRPS162/165D) but not the non-phosphorylatable mutant of CRP (CRPS162/165A) interacts with RNA-binding protein UBP1-associated protein 2C (TaUBA2C). Silencing of TaUBA2C expression in wheat plants enhanced CWMV infection. In contrast, overexpression of TaUBA2C in wheat plants inhibited CWMV infection. TaUBA2C inhibits CWMV infection through recruiting the pre-mRNA of TaNPR1, TaPR1 and TaRBOHD to induce cell death and H2O2 production. This effect can be supressed by CRPS162/165D through changing TaUBA2C chromatin-bound status and attenuating it's the RNA- or DNA-binding activities. Taken together, our findings provide new knowledge on how CRP phosphorylation affects CWMV infection as well as the arms race between virus and wheat plants.

Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia.

Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified. Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored. Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group. Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.

Quality assessment of Succus Bambusae oral liquids based on gas chromatography/mass spectrometry fingerprints and chemometrics.

RATIONALE: Succus Bambusae is consumed as a kind of herbal medicine and natural beverage in China. However, the current quality standards for Succus Bambusae are low and lack safety indicators, which makes it difficult to effectively guarantee its quality. Therefore, it is of great significance to study the identification and quality control technology for the product. METHODS: We have developed a set of qualitative and quantitative methods based on gas chromatography/mass spectrometry (GC/MS) for the analysis of volatile components in Succus Bambusae oral liquid (SBOL). Combining GC/MS fingerprint analysis and related chemometrics algorithms, with similarity evaluation, Hotelling T2 and distance to Model X (DModX) as criteria, the quality consistency of different batches was evaluated, and SBOL samples from different manufacturers were differentiated. RESULTS: Twenty-nine volatile components were preliminarily identified from 40 batches of SBOL samples from six manufacturers, and six Q-markers (Quality Markers) for the SBOLs were discussed and determined using GC/MS. The products from different manufacturers were distinguished using chemometrics. CONCLUSIONS: The results showed that the quality of the SBOL samples from different batches and different manufacturers fluctuated greatly, which suggested that research into the raw materials and manufacturing techniques should be strengthened to improve the quality of SBOL and ensure its quality consistency.

Transverse and longitudinal coupling of LSPPs in isolated triangular Al-SiO2-Al hybrid nanoplates for generation of local electromagnetic fields with enhanced intensity and increased decay time.

Achieving a large enhancement of local electromagnetic fields in the ultraviolet waveband is desirable for some applications such as surface-enhanced Raman scattering and surface-enhanced fluorescence. In addition, it is more significant for some applications such as plasmon-enhanced harmonic generation to enhance the intensity of local electromagnetic fields and increase their decay time at the same time. In this paper, using the finite-difference time-domain method, we numerically demonstrate that using the linearly polarized light with a wavelength of 325 nm as the illumination light, an isolated triangular Al-SiO2-Al hybrid nanoplate with optimized geometric parameters can produce a local electric field enhanced by a factor of about 108 at one of its top apexes, and produce two local electric fields enhanced by a factor of about 150 at two transverse dielectric/metal interfaces of one of its longitudinal side edges. Moreover, we also numerically demonstrate that the decay time of enhanced local electric fields produced by the isolated triangular Al-SiO2-Al hybrid nanoplate is about 1.6 times as large as that of enhanced local electric fields produced by an isolated triangular Al nanoplate. These unique properties of the isolated triangular Al-SiO2-Al hybrid nanoplate arise because of both the transverse coupling and the longitudinal coupling of localized surface plasmon polaritons in this structure. Our findings make triangular Al-SiO2-Al hybrid nanoplates very promising for application in many fields such as surface-enhanced Raman scattering and plasmon-enhanced harmonic generation.

[Comparative study on the clinical features of familial clustered and sporadic vestibular migraine].

Objective:To compare and analyze the clinical features of family clustered vestibular migraine（FCVM） and sporadic vestibular migraine（SVM）. Methods:A total of 118 patients with vestibular migraine were selected and divided into FCVM group（66 cases） and SVM group（52 cases）, and the clinical features such as age, the form of symptoms, provoking and relieving factors, audiological manifestations, sequelae and complications, were compared and analyzed. Results:The onset of headache in FCVM group was earlier than that in SVM group （[23.88±11.45] years old and [28.77±11.85] years old, χ²=2.267, P=0.025） with a longer interval between headache and vertigo attack （[13.11±10.08] years old and [8.50±9.26] years old, χ²=2.554, P=0.012）.Patients with positional vertigo in the FCVM group were more than those in the SVM group （12[18.2%] and 0[0], χ²=3.171, P=0.002）. Mental anxiety（P<0.001）, neck stiffness（P=0.028）, and concentration difficulties（P=0.001） were more common in patients with FCVM at the end of the episode than in patients with SVM. Comorbid primary motion sickness combined was more common in FCVM group than in SVM group（49 cases[74.2%] and 25 cases[48.1%], χ²=2.906, P=0.004）. Conclusion:The onset of FCVM is earlier and the prognosis is often poor. Primary motion sickness can be used as a reference for the early diagnosis of FCVM.

Synthesis of Copolymers Polyethyleneimine-co-Polyphenylalanine as Gene and Drug Codelivery Carrier.

In this study, a series of hyperbranched copolymers polyethyleneimine-co-polyphenylalanine (PEI-co-PPhe) are synthesized by ring-opening polymerization with phenylalanine-N-carboxyanhydride as monomer and PEI-25k as initiator, using as a gene and drug codelivery carrier. Among them, PEI-co-PPhe (1:170) is selected out from transfection efficiency and cytotoxicity tests. Then, doxorubicin-cis-aconitic anhydride (CAD) and BCl2-shRNA (as a therapeutic gene) are coloaded into the PEI-co-PPhe carrier to form PEI-co-PPhe/Bcl2-shRNA/CAD complexes as a codeliver system. When the mass ratio of PEI-co-PPhe:Bcl2-shRNA:CAD is 5:1:1, the codeliver system has the most obvious synergistic therapeutic effect against B16F10 cells. Confirmed by confocal laser scanning microscope and flow cytometry, compared with drug and gene alone, the codeliver complexes can be endocytosed into B16F10 cells efficiently. As a result, the appropriate length of PPhe grafted on PEI will improve the gene transfer efficiency and decrease cytotoxicity, as well as effective codelivery of gene and drug into cancer cells to be a promising codelivery carrier for cancer therapy.

Health risk assessment of total exposure from cadmium in South China.

Heavy metal pollution and hazards are a global major concern. Heavy metals can be directly or indirectly harmful to humans through ingestion, inhalation, and deraml. According to the literature survey, cadmium (Cd) total exposure assessment and health risk assessment were performed in a population group from South China. Results showed that the Cd contents in PM2.5 and vegetables exceeded national standard limits. The same sources of Cd pollution contributed to different media; the main sources were artificial industrial activities such as electroplating, mining and smelting. The average daily dose of Cd via ingestion exceeded the provisional tolerable monthly intake proposed by the Joint Expert Committee on Food Additives (JECFA). Multimedia exposure via all three pathways followed the order 0-5-year-old children (3.26 × 10-3 mg kg-1·d-1)>6-17-year-old children (1.46 × 10-3 mg kg-1·d-1)>adults (1.18 × 10-3 mg kg-1·d-1). The exposure from point source pollution was quite different from the results for nonpoint sources. Ingestion was the exposure pathway that contributes the largest proportion of multipathway and multimedia total exposure, accounting for over 99% of the total exposure in different populations. Staple foods, vegetables and meat were the three main exposure media for ingestion. The hazard quotients of multipathway and multimedia exposure to Cd in different populations were 5.57, 2.87 and 2.26, respectively, all at unacceptable risk levels. This study highlights the importance of multipathway and multimedia in the health risk assessment of heavy metal exposure in South China, and provides risk management measures to reduce noncarcinogenic health risks.

Carotid imaging changes and serum IL-1ß, sICAM-1, and sVAP-1 levels in benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo. This study was performed to evaluate serum levels of inflammatory factors and changes in B-mode carotid ultrasound findings in patients with BPPV. The study population consisted of 90 BPPV patients and 90 age- and sex-matched controls. ELISA was used to compare the levels of inflammatory factors, such as interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin-E2 (PG-E2), and soluble vascular adhesion protein-1 (sVAP-1), between BPPV patients and controls. In addition, the results of ultrasonographic imaging to determine carotid intima-media thickness (C-IMT), carotid atheromatous plaque, and vertebral artery stenosis were also compared between the BPPV and control groups. Serum levels of IL-1ß, sICAM-1, and sVAP-1 were significantly higher in BPPV patients than controls (P < 0.001, P < 0.05, and P < 0.001, respectively). C-IMT and vertebral artery stenosis were significantly different in BPPV patients compared to controls (both P < 0.05). There were no significant relations between other parameters and BPPV. IL-1ß, sICAM-1, and sVAP-1 are potentially associated with the pathogenesis of BPPV, and C-ITM and carotid vertebral stenosis may be useful reference imaging findings for the diagnosis of BPPV.

The tRNA-like small noncoding RNA mascRNA promotes global protein translation.

mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi-tRNA synthetase complex (MSC) component glutaminyl-tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA-like structures in mammalian cells.

Isolation, identification, and biological control in vitro of tail rot pathogen strain from Hippocampus kuda.

Tail rot disease is associated with major economic losses in the seahorse aquaculture in China. This study aimed to isolate and identify the pathogen causing tail rot disease in seahorses. Three culturable intestinal bacteria strains were isolated from Hippocampus kuda specimens with tail rot disease. Strain HL11, HL12, and HL13 were identified as Pseudoalteromonas spongiae, Bacillus subtilis and Photobacterium ganghwense based on its morphological characteristics, physiological and biochemical properties, through 16S rRNA and gyrB sequencing, respectively. Challenge experiments using these strains on healthy H. kuda and bacterial re-isolation from challenged diseased seahorses showed that the bacteria strain named HL11 induced identical pathological symptoms, indicating that it is the causative pathogen of the disease. Antibiotic-resistance tests against of 32 antibiotics revealed that HL11 was highly sensitive to 13 kinds, while exhibited intermediate susceptibility to 6, and resistance to 13 kinds. Antibacterial tests of the bioactive agents showed that HL11 was susceptible to five kinds, including tea polyphenols, lactic acid, gallic acid, allicin, and polylysine; however, it was not susceptible to the other 13 kinds of bioactive agents. The results demonstrate the potential of using bioactive agents to replace antibiotics to generate an environmentally friendly mode of culturing seahorses.

Function of NHX-type transporters in improving rice tolerance to aluminum stress and soil acidity.

MAIN CONCLUSION: In this study, we show that ectopic expression of either HtNHX1 or HtNHX2, from Helianthus tuberosus plant (located at vacuolar and endosome membranes, respectively), in rice plants could enhance its tolerance to aluminum (Al3+) stress and soil acidity. Plant sodium (potassium)/proton (Na+(K+)/H+ antiporters of the NHX family have been extensively characterized as they are related to the enhancement of salt tolerance. However, no previous study has reported NHX transporter functions in plant tolerance to Al3+ toxicity. In this study, we demonstrate their role as a component of the Al3+ stress tolerance mechanism. We show that the ectopic expression of either HtNHX1 or HtNHX2 , from Helianthus tuberosus plant, in rice (located at vacuole and endosome, respectively) could also enhance rice tolerance to Al3+ stress and soil acidity. Expression of either HtNHX1 or HtNHX2 reduced the inhibitory effect of Al3+ on the rice root elongation rate; both genes were reported to be equally effective in improvement of stress conditions. Expression of HtNHX1 enhanced Al3+-trigged-secretion of citrate acids, rhizosphere acidification, and also reduced K+ efflux from root tissues. In contrast, expression of HtNHX2 prevented Al3+-trigged-decrease of H+ influx into root tissues. Al3+-induced damage of the cell wall extensibility at the root tips was impaired by either HtNHX1 or HtNHX2. Co-expression of HtNHX1 and HtNHX2 further improved rice growth, particularly under the Al3+ stress conditions. The results demonstrate that HtNHX1 and HtNHX2 improved rice tolerance to Al3+ via different mechanisms by altering the K+ and H+ fluxes and the cell wall structure.

A Novel Transcriptome Integrated Network Approach Identifies the Key Driver lncRNA Involved in Cell Cycle With Chromium (VI)-Treated BEAS-2B Cells.

Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 µmol/L for 24 h. Here, we identified 1,484 differentially expressed genes (DEGs) in our transcript profiling data, with the majority of differentially expressed transcripts being downregulated. Our results also showed that these DEGs were enriched in pathways associated with the cell cycle, including DNA replication, chromatin assembly, and DNA repair. Using the differential expressed genes related to cell cycle, a weighted gene co-expression network was constructed and a key mRNA-lncRNA regulation module was identified under a scale-free network with topological properties. Additionally, key driver analysis (KDA) was applied to the mRNA-lncRNA regulation module to identify the driver genes. The KDA revealed that ARD3 (FDR = 1.46 × 10-22), SND1 (FDR = 5.24 × 10-8), and lnc-DHX32-2:1 (FDR = 1.43 × 10-17) were particularly highlighted in the category of G2/M, G1/S, and M phases. Moreover, several genes we identified exhibited great connectivity in our causal gene network with every key driver gene, including CDK14, POLA1, lnc-NCS1-2:1, and lnc-FOXK1-4:1 (all FDR < 0.05 in those phases). Together, these results obtained using mathematical approaches and bioinformatics algorithmics might provide potential new mechanisms involved in the cytotoxicity induced by Cr.