Tetraarsenic tetrasulfide triggers ROS-induced apoptosis and ferroptosis in B-cell acute lymphoblastic leukaemia by targeting HK2.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. Despite cure rates of higher than 85 %, refractory or relapsed ALL still exhibits a bleak prognosis indicative of the dearth of treatment modalities specific for relapsed or refractory ALL. Prior research has implicated metabolic alterations in leukemia pathogenesis, and literature on the therapeutic efficacy of arsenic compounds targeting metabolic pathways in B-cell acute lymphoblastic leukemia (B-ALL) cells is scarce. METHODS: A compound extracted from realgar, tetraarsenic tetrasulfide (As4S4), and its antitumor effects on B-ALL were experimentally examined in vitro and in vivo. RESULTS: As4S4 apparently targets B-ALL cells by inducing specific cellular responses, including apoptosis, G2/M arrest, and ferroptosis. Interestingly, these effects are attributed to reactive oxygen species (ROS) accumulation, and increased ROS levels have been linked to both the mitochondria-dependent caspase cascade and the activation of p53 signaling. The ROS scavenger N-acetylcysteine (NAC) can counteract the effects of As4S4 treatment on Nalm-6 and RS4;11 cells. Specifically, by targeting Hexokinase-2 (HK2), As4S4 induces alterations in mitochondrial membrane potential and disrupts glucose metabolism, leading to ROS accumulation, and was shown to inhibit B-ALL cell proliferation in vitro and in vivo. Intriguingly, overexpression of HK2 can partially desensitize B-ALL cells to As4S4 treatment. CONCLUSION: Tetraarsenic tetrasulfide can regulate the Warburg effect by controlling HK2 expression, a finding that provides both new mechanistic insight into metabolic alterations and pharmacological evidence for the clinical treatment of B-ALL.

Effectiveness and Safety of Sacubitril/Valsartan in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Objective: Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context, the objective of this meta-analysis is to evaluate the effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in managing HFpEF. Methods: A systematic search of relevant studies was conducted in PubMed, Embase, Web of Science, and Cochrane Library. Randomized controlled trials comparing sacubitril/valsartan to ACEIs or ARBs in HFpEF patients were included. Inclusion criteria: LVEF>45%, NYHA II-IV, Sac/Val vs ACEI/ARB, RCTs, treatment duration >3 months, sample size ≥25 per group. Exclusion criteria: Animal studies, unclear/missing data, poor quality, case studies/expert opinions.Hospitalization for heart failure and cardiovascular mortality were the primary outcomes, while the additional results included mortality from all causes, improvement of NYHA class, modifications in NT-proBNP, and with LVEF. Results: Sacubitril/valsartan substantially reduced heart failure hospitalization rates compared to ACEIs and ARBs, according to a total of six studies involving 5,201 participants (Relative Risk, 0.78; 95% CI, 0.65 to 0.85; P = .001). Nonetheless, there were no significant improvements in mortality due to cardiovascular disease (Relative Risk, 0.94; 95% CI, 0.79-1.12; P = .563). Sacubitril/valsartan did not affect total mortality from all causes significantly (Relative Risk, 0.95; 95% CI, 0.84-1.09; P = .453), but it did enhance NYHA classification (Relative Risk, 1.25; 95% CI, 1.10-1.43; P = .001). NT-proBNP levels decreased substantially (Weighted Mean Difference, -266.67; 95% CI, -525.86 to -7.47), whereas there had been little major shift in LVEF (Weighted Mean Difference, 1.49; 95% CI, -1.33 to 4.21; P = .342). Conclusions: Sacubitril/valsartan may provide superior benefits in reducing heart failure hospitalization rates, NT-proBNP levels, and improving NYHA classification in patients with HFpEF compared to ACEIs and ARBs. Sacubitril/valsartan might be considered as a preferred treatment option for HFpEF patients due to its benefits in reducing heart failure hospitalization rates and improving symptom severity.

Methyl jasmonate and selenium synergistically mitigative cadmium toxicity in hot pepper (Capsicum annuum L.) plants by improving antioxidase activities and reducing Cd accumulation.

Methyl jasmonate (MeJA) or selenium (Se)-mediated response to cadmium (Cd) stress in plant has been widely reported, but the combined effects both on plant growth in response to Cd stress and the underlying mechanisms remain obscure. Here, we showed the combined effects of MeJA (2.5 µM) and Se (7 µM) on hot pepper growth under Cd stress (CdCl2, 5 µM). The results showed Cd suppressed the accumulation of total chlorophyll and carotenoid and reduced the photosynthesis, while it increased the content of endogenous signaling molecules, e.g. nitric oxide (NO) and hydrogen peroxide (H2O2), as well as Cd content in leaves. The combined application of MeJA and Se significantly decreased the malondialdehyde (MDA) accumulation and improved the activities of antioxidant enzymes (AOEs, e.g. SOD and CAT) and defense-related enzymes (DREs, POD and PAL). Additionally, the synergistic application of MeJA and Se also obviously improved photosynthesis in hot pepper plants under Cd stress compared with those treated with MeJA or Se respectively or not. Moreover, the treatment of MeJA associated with Se also effectively reduced the Cd accumulation in hot pepper leaves under Cd stress compared with the plants treated with MeJA or Se separately, which implied a potentially synergistic role of MeJA and Se in alleviating Cd toxicity in hot pepper plants. This study provides a theoretical reference for the further analysis of the molecular mechanism of MeJA and Se in jointly mediating the response to heavy metals in plants.

Complete Genome Sequence of Bacillus licheniformis Strain GN02, Isolated from the Root Surface of Brassica chinensis.

Bacillus licheniformis GN02 was isolated from the root surface of Pak Choi Cabbage (Brassica chinensis). Here, we report the whole-genome sequence of strain GN02, which includes only a circular chromosome (4,252,022 bp; GC content, 46.08%).

Identification of a Coprinellus strain and its application in Eucommia ulmoides gum extraction by fermenting leaves.

White rot fungi is a kind of filamentous fungi which can degrade lignin, hemicellulose and cellulose effectively. In this study, a wild white rot fungi collected from Pingba Town, Bijie City of China was identified as Coprinellus disseminatus (fruiting body) based on morphological and molecular identification. The mycelium of C. disseminatus cultured in the medium supplemented xylan as carbon showed the higher xylanase (XLE) and cellulase (CLE) activity. Further, the activities of tissue degradation-related enzymes including XLE, CLE, acetyl xylanesterase (AXE) and α-L-arabinofuran glycosidase (α-L-AF) were determined after fermenting Eucommia ulmoides leaves by inoculating C. disseminatus mycelium. The results showed that the activities of XLE, CLE, AXE and α-L-AF of mycelium cultured in xylan-contained medium reached the maximum at 5 d after inoculation, which were 777.606 ± 4.248 U mL-1, 9.594 ± 0.008 U mL-1, 4.567 ± 0.026 U mL-1 and 3.497 ± 0.10 U mL-1 respectively. Also, the activities of AXE and α-L-AF both reached the maximum in C. disseminatus mycelium cultured in glucose-contained medium. By comparing the yield of E. ulmoides gum under different fermentation treatments, the extraction yield of E. ulmoides gum were 2.156 ± 0.031% and 2.142 ± 0.044% at 7 d and 14 d after fermentation with mycelium supplemented xylan as carbon source, which were significantly higher than other groups. This study provides a theoretical reference for the preparation of E. ulmoides gum by large-scale fermentation of E. ulmoides leaves with C. disseminatus.

Atomic/Molecular Layer-Deposited Laminated Li2O-Lithicone Interfaces Enabling High-Performance Silicon Anodes.

Silicon-based materials are of long-standing interest as the anodes for next-generation lithium-ion batteries, yet their low initial Coulombic efficiency and poor interfacial stability are lethal limitations. In this work, we used atomic layer deposition (ALD) and molecular layer deposition (MLD) techniques to fabricate a lithium-containing laminated Li2O-lithicone hybrid film (∼5 nm) on a silicon electrode. The laminated film provides an additional surface Li source around silicon cores, which can partially reimburse the Li loss during battery cycling. Characterization of interfacial components shows that such a laminated Li2O-lithicone interface undergoes gentle element changes and participates in a hybrid solid electrolyte interphase with Li2CO3, Li2O, LixPOFy, and LiF species. Finite element model analysis and morphology characterization demonstrate that the laminated structure design can help relieve the interfacial stress and thus retain the integrity and reactivity of the silicon composite anode during cycling. Moreover, the lithium-based laminated film leads to a fast Li+ migration kinetics on the surface of the electrode as revealed by the galvanostatic intermittent titration technique and density functional theory calculation. Benefiting from the above merits, a silicon anode with a 91.2% initial Coulombic efficiency, a rate performance of 1460 mA h g-1 at 2 A g-1, and a reversible capacity over 646 mA h g-1 after 850 cycles was achieved. This work exemplifies the advantages of lithium-based hybrid films precisely engineered by ALD/MLD techniques for improving performances of advanced silicon anode batteries and deepens understandings on the mechanism of interfacial stability and reaction kinetics.

Bacillus paralicheniformis RP01 Enhances the Expression of Growth-Related Genes in Cotton and Promotes Plant Growth by Altering Microbiota inside and outside the Root.

Plant growth-promoting bacteria (PGPB) can promote plant growth in various ways, allowing PGPB to replace chemical fertilizers to avoid environmental pollution. PGPB is also used for bioremediation and in plant pathogen control. The isolation and evaluation of PGPB are essential not only for practical applications, but also for basic research. Currently, the known PGPB strains are limited, and their functions are not fully understood. Therefore, the growth-promoting mechanism needs to be further explored and improved. The Bacillus paralicheniformis RP01 strain with beneficial growth-promoting activity was screened from the root surface of Brassica chinensis using a phosphate-solubilizing medium. RP01 inoculation significantly increased plant root length and brassinosteroid content and upregulated the expression of growth-related genes. Simultaneously, it increased the number of beneficial bacteria that promoted plant growth and reduced the number of detrimental bacteria. The genome annotation findings also revealed that RP01 possesses a variety of growth-promoting mechanisms and a tremendous growth-promoting potential. This study isolated a highly potential PGPB and elucidated its possible direct and indirect growth-promoting mechanisms. Our study results will help enrich the PGPB library and provide a reference for plant-microbe interactions.

Heterologous expression of HsPstS gene reducing arsenic accumulation and improving As-tolerance in transgenic tobaccos by enhancing CAT activity.

Arsenic (As) is a toxic metalloid element that affects plant growth and development. Reducing the uptake of arsenic by plants via genetic engineering strategy can effectively improve the tolerance and safety of economic crops in As-contaminated soil. In this paper, the HsPstS gene coded ABC-type periplasmic phosphate-binding protein (PBP) of Halomonas strain GFAJ-1 was introduced into tobacco K326 by Agrobacterium-mediated genetic transformation to create transgenic tobaccos. Under As stress, NBT and DAB staining of tobacco leaves showed significant accumulation of H2O2 in wild-type and CK plants, and the further determination showed that the H2O2 content in CK plants was higher than that in transgenic plants except for L35S-2 and LREL-4 at 3 d after stress. Generally, the activity of antioxidant enzymes (CAT and POD) in tobaccos increased first and then decreased under As stress, and the CAT activity in most transgenic tobacco plants was significantly higher than that in wild-type and CK plants at 5 d after stress. By contrast, POD activity in CK and wild-type plants was significantly higher than that in transgenic tobaccos except for L35S-2. Additionally, As content determination showed that all transgenic tobacco plants except for CK showed the characteristic of low As-accumulation, especially in transgenic tobaccos L35S-2 and LREL-4, which suggested that the introduction of HsPstS could significantly reduce the As absorption in HsPstS-contained transgenic tobaccos, while there was no significant influence on agronomic traits and photosynthetic characteristics of transgenic tobaccos compared with wild-type ones. Interestingly, the introduction of HsPstS gene also reduced the content of nicotine and nornicotine in transgenic tobacco plants, while there was no significant difference on K content between transgenic and non-transgenic tobaccos. These results above provided ideal parental materials for cultivating tobacco germplasm with the characteristic of low As-accumulation.

Objective sleep characteristics and continuous glucose monitoring profiles of type 2 diabetes patients in real-life settings.

AIM: To investigate the association between objective sleep parameters and glycaemic variability determined by continous glucose monitoring (CGM) among patients with type 2 diabetes, given the significant role of sleep in glycaemic control. METHODS: In this study, CGM was carried out in 28 patients with T2D (aged 62.3 ± 4.8 years, 57% women). Sleep characteristics were assessed by actigraphy within the CGM period. CGM-derived outcomes included glucose level, and percentages of time in range (TIR) and time above range (TAR) during the monitoring period. Associations between intraindividual night-to-night variations in sleep characteristics and overall CGM outcomes were analysed using linear regression. Associations between sleep characteristics during each night and time-matched CGM outcomes were analysed using linear mixed models. RESULTS: A total of 249 person-days of CGM, coupled with 221 nights of sleep characteristics, were documented. Greater standard deviation (SD) of objective sleep duration (minutes) between measurement nights was associated with higher glucose level (coefficient 0.018 mmol/L [95% confidence interval {CI} 0.004, 0.033], P = 0.017), smaller proportion of TIR (% in observation period; coefficient -0.20% [95% CI -0.36, -0.03], P = 0.023), and greater proportion of TAR (coefficient 0.22% [95% CI 0.06, 0.39], P = 0.011). Later sleep midpoint (minutes from midnight) was associated with greater SD of glucose during the same sleep period (coefficient 0.002 minutes [95% CI 0.0001, 0.003], P = 0.037), longer nocturnal sleep duration was associated with smaller coefficient of variation of glucose level in the upcoming day (-0.015% [95% CI -0.03, -0.001], P = 0.041). CONCLUSION: Objectively determined sleep duration and sleep midpoint, as well as their daily variability, are associated with CGM-derived glucose profiles in T2D patients.

Effects of Microbial Transfer during Food-Gut-Feces Circulation on the Health of Bombyx mori.

Change in habitual diet may negatively affect health. The domestic silkworm (Bombyx mori) is an economically important oligophagous insect that feeds on mulberry leaves. The growth, development, and immune-disease resistance of silkworms have declined under artificial dietary conditions. In this study, we used B. mori as a model insect to explore the relationship between changes in diet and balance of intestinal microbes due to its simpler guts compared with those of mammals. We found that artificial diets reduced the intestinal bacterial diversity in silkworms and resulted in a simple intestinal microbial structure. By analyzing the correlations among food, gut, and fecal microbial diversity, we found that an artificial diet was more easily fermented and enriched the lactic acid bacteria in the gut of the silkworms. This diet caused intestinal acidification and microbial imbalance (dysbiosis). When combined with the artificial diet, Enterococcus mundtii, a colonizing opportunistic pathogen, caused dysbiosis and allowed the frequent outbreak of bacterial diseases in the silkworms. This study provides further systematic indicators and technical references for future investigations of the relationship between diet-based environmental changes and intestinal microbial balance. IMPORTANCE The body often appears unwell after habitual dietary changes. The domestic silkworm (Bombyx mori) raised on artificial diets is a good model to explore the relationship between dietary changes and the balance of intestinal microbes. In this study, the food-gut-feces microbial model was established, and some potential key genera that could regulate the balance of intestinal microbiota were screened out. Our findings will provide a reference for future research to further our understanding of healthy silkworm development and may even be useful for similar research on other animals.

Primary erythromelalgia mainly manifested by hypertensive crisis: A case report and literature review.

Background: Primary erythrocytic (PEM) is a rare autosomal dominant single gene disease. Most of the changes of gene loci can be found by whole exon gene sequencing, and the clinical symptoms and patient survival can be improved by specific site-to-site drug treatment. The other manifestations of this patient population are not remarkable. After the application of common drugs, the toxicity and side effects can be limiting. In addition to other common clinical manifestations, we found that the only unique manifestation of this patient was hypertensive crisis. Following multidisciplinary diagnosis and treatment (MDT), we decided to first control hypertension to alleviate the acute and critical patients. However, after controlling the hypertensive crisis, we unexpectedly found that the clinical symptoms of the patients had been significantly improved. Therefore, we concluded that the use of antihypertensive drugs can treat erythematous limb pain with the clinical manifestation of hypertensive crisis. Here, we describe a typical PEM disease, primary clinical features, diagnosis and treatment. Methods: Medical records of an 8-year-old boy with PEM were analyzed retrospectively, which included clinical characteristics, follow-up information, and SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9) gene analysis. Results: The 8-year-old boy had complained of abnormal paresthesia in his feet and ankles with burning sensation and pain for 2 years. The skin of both lower legs was red and underwent ichthyosis and lichenification. Genetic analysis confirmed the existence of a SCN9A gene mutation. The symptoms were gradually improved by treating with intravenous drip and oral administration of nitroglycerin to slow his heart rhythm. Conclusion: Primary erythrocytic is characterized by skin ulceration, redness, elevated temperature, and severe burning pain primarily in both lower extremities. PEM can be diagnosed by genetic analysis. As this case demonstrates, treating with nitroglycerin as the drug of choice to control the hypertensive crisis significantly improved the symptoms of PEM and hypertension in this patient.

Genome-wide identification and genetic characterization of the CaMYB family and its response to five types of heavy metal stress in hot pepper (Capsicum annuum cv. CM334).

MYB proteins play a crucial role in plant growth and development and stress responses. In this study, 160 members of the MYB gene family from the pepper genome database were used to analyze gene structures, chromosome localization, collinearity, genetic affinity and expression in response to heavy metals. The results identified R2R3-MYB members and further phylogenetically classified them into 35 subgroups based on highly conserved gene structures and motifs. Collinearity analysis showed that segmental duplication events played a crucial role in the functional expansion of the CaMYB gene family by intraspecific collinearity, and at least 12 pairs of CaMYB genes existed between species prior to the differentiation between monocots and dicots. Moreover, the upstream CaMYB genes were mainly localized to the phytohormone elements ABRE and transcription factor elements MYB and MYC. Further analysis revealed that MYB transcription factors were closely associated with a variety of abiotic stress-related proteins (e.g., MAC-complex and SKIP). Under the stress of five metal ions, Cd2+, Cu2+, Pb2+, Zn2+, and Fe3+, the expression levels of some CaMYB family genes were upregulated. Of these genes, pairing homologous 1 (PH-1), PH-13, and PH-15 in the roots of Capsicum annuum were upregulated to the greatest extent, indicating that these three MYB family members are particularly sensitive to these five metals. This study provides a theoretical reference for the analysis of the molecular regulatory mechanism of MYB family genes in mediating the response to heavy metals in plants. This study reveals the mode of interaction between MYB and a variety of abiotic stress proteins and clarifies the biological functions of CaMYB family members in the regulation of heavy metal stress.

Bacillus circulans GN03 Alters the Microbiota, Promotes Cotton Seedling Growth and Disease Resistance, and Increases the Expression of Phytohormone Synthesis and Disease Resistance-Related Genes.

Plant growth-promoting bacteria (PGPB) are components of the plant rhizosphere that promote plant growth and/or inhibit pathogen activity. To explore the cotton seedlings response to Bacillus circulans GN03 with high efficiency of plant growth promotion and disease resistance, a pot experiment was carried out, in which inoculations levels of GN03 were set at 104 and 108 cfu⋅mL-1. The results showed that GN03 inoculation remarkably enhanced growth promotion as well as disease resistance of cotton seedlings. GN03 inoculation altered the microbiota in and around the plant roots, led to a significant accumulation of growth-related hormones (indole acetic acid, gibberellic acid, and brassinosteroid) and disease resistance-related hormones (salicylic acid and jasmonic acid) in cotton seedlings, as determined with ELISA, up-regulated the expression of phytohormone synthesis-related genes (EDS1, AOC1, BES1, and GA20ox), auxin transporter gene (Aux1), and disease-resistance genes (NPR1 and PR1). Comparative genomic analyses was performed between GN03 and four similar species, with regards to phenotype, biochemical characteristics, and gene function. This study provides valuable information for applying the PGPB alternative, GN03, as a plant growth and disease-resistance promoting fertilizer.

Identification of novel heavy metal detoxification proteins in Solanum tuberosum: Insights to improve food security protection from metal ion stress.

With increasingly serious environmental pollution problems, research has focused on identifying functional genes within plants that can help ensure food security and soil governance. In particular, plants seem to have been able to evolve specific functional genes to respond to environmental changes by losing partial gene functions, thereby representing a novel adaptation mechanism. Herein, a new category of functional genes was identified and investigated, providing new directions for understanding heavy metal detoxification mechanisms. Interestingly, this category of proteins appears to exhibit specific complexing functions for heavy metals. Further, a new approach was established to evaluate ATP-binding cassette (ABC) transporter family functions using microRNA targeted inhibition. Moreover, mutant and functional genes were identified for future research targets. Expression profiling under five heavy metal stress treatments provided an important framework to further study defense responses of plants to metal exposure. In conclusion, the new insights identified here provide a theoretical basis and reference to better understand the mechanisms of heavy metal tolerance in potato plants. Further, these new data provide additional directions and foundations for mining gene resources for heavy metal tolerance genes to improve safe, green crop production and plant treatment of heavy metal soil pollution.

Genome-wide analysis of the NRAMP gene family in potato (Solanum tuberosum): Identification, expression analysis and response to five heavy metals stress.

NRAMP family genes participate in the absorption and transport of heavy metals such as cadmium (Cd), zinc (Zn), copper (Cu), lead (Pb), iron (Fe) and manganese (Mn) and play an important role in the response to heavy metal stress. There is an abundance of research on these genes in bacteria, plants and fungi, although not in S. tuberosum. A total of 48 members(potato(5), Arabidopsis(7), Tomato(9), pepper(9), rice(12) and tobacco(6)) were identified from 6 species (potato (Solanum tuberosum), Arabidopsis thaliana, Tomato (Solanum lycopersicum), pepper (Capsicum annuum), rice (Oryza sativa) and tobacco (Nicotiana attenuate)) and were classified into four subgroups. Across NRAMP gene family members, there are 15 highly conserved motifs that have similar genetic structures and characteristics. In addition, a total of 16 pairs of colinear genes were found in eight species. Analysis of cis-elements indicated that, in response to abiotic stress, NRAMPs are mainly regulated by phytohormones and transcription factors. In addition, analysis of expression profiles indicated that StNRAMP4 is mainly expressed in the roots. According to a qRT-PCR-based analysis of the StNRAMP family, with the exception of Pb2+ stress, StNRAMPs positively responded to stress from Cu2+, Cd2+, Zn2+ and Ni2+ and The expression patterns is similar of StNRAMP2, under Pb2+, and Cu2+ treatment, the relative expression peaked at 24 h. the relative expression peaked at 12 h and was upregulated 428-fold in the roots under Ni2+ stress. Under Cd2+ stress, StNRAMP3 was upregulated 28-fold in the leaves. StNRAMP1, StNRAMP4 and StNRAMP5 showed significant upregulation under Cu2+, Cd2+ and Zn2+ stress, respectively. Expression of StNRAMPs could be specifically induced by heavy metals, implying their possible role in the transport and absorption of heavy metals. This research explains the colinear characteristics of NRAMPs in several food crop species, which is useful for providing important genetic resources for cultivating food crop that accumulate low amounts of heavy metals and for explaining the biological functions of NRAMPs in plants.

Heavy Metal Transporters-Associated Proteins in S. tuberosum: Genome-Wide Identification, Comprehensive Gene Feature, Evolution and Expression Analysis.

Plants have evolved a number of defense and adaptation responses to protect themselves against challenging environmental stresses. Genes containing a heavy metal associated (HMA) domain are required for the spatiotemporal transportation of metal ions that bind with various enzymes and co-factors within the cell. To uncover the underlying mechanisms mediated by StHMA genes, we identified 36 gene members in the StHMA family and divided them into six subfamilies by phylogenetic analysis. The StHMAs had high collinearity and were segmentally duplicated. Structurally, most StHMAs had one HMA domain, StHIPPc and StRNA1 subfamilies had two, and 13 StHMAs may be genetically variable. The StHMA gene structures and motifs varied considerably among the various classifications, this suggests the StHMA family is diverse in genetic functions. The promoter analysis showed that the StHMAs had six main cis-acting elements with abiotic stress. An expression pattern analysis revealed that the StHMAs were expressed tissue specifically, and a variety of abiotic stresses may induce the expression of StHMA family genes. The HMA transporter family may be regulated and expressed by a series of complex signal networks under abiotic stress. The results of this study may help to establish a theoretical foundation for further research investigating the functions of HMA genes in S. tuberosum to elucidate their regulatory role in the mechanism governing the response of plants to abiotic stress.

Insights from the Complete Genome Sequence of Bacillus circulans GN03, a Plant Growth-Promoting Bacterium Isolated from Pak Choi Cabbage (Brassica chinensis L.) Root Surface.

A plant growth-promoting rhizobacterium, Bacillus circulans GN03, was isolated from the root surface of pak choi cabbage. Here, we report the whole-genome sequence of the GN03 strain, which includes a circular chromosome (5,217,129 bp; GC content, 35.64%) and a plasmid (181,705 bp; GC content, 31.62%).

miR-15a regulates oxygen glucose deprivation/reperfusion (OGD/R)-induced neuronal injury by targeting BDNF.

Multiple microRNAs (miRs) have also been implicated in ischemic brain injury. This research intended to probe the regulatory function and the mechanism of miR-15a on the ischemic brain injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in neurons of rats. The OGD/R model was established with the cortical neurons separated from rats. After transfection with miR-15a mimic negative control (NC), miR-15a mimic, miR-15a inhibitor NC and miR-15a inhibitor, the OGD/R-induced apoptosis were detected. Using bioinformatic softwares including TargetScan, miRanda, and miRWalk to predict the underlying targets of miR-15a, and the binding of miR-15a with brain-derived neurotrophic factor (BDNF) were validated with double-fluorescein reporter assay system. The expression levels of BDNF mRNA and protein were detected with qRT-PCR and western blot. The effect of miR-15a on PI3K/AKT pathway in neurons submitted to OGD/R was also investigated. The findings showed that miR-15a may mediate the apoptosis of neurons submitted to OGD/R, and lower expression of Bcl-2 and higher expression of Bax and cleaved caspase-3 were observed. BDNF was screened as the candidate target, and the direct binding of miR-15a with 3'-UTR of BDNF were verified. Further research showed that miR-15a downregulated the expression of BDNF mRNA and protein, thus exerted negative regulatory effect on the OGD/R injury. PI3K/AKT pathway may be related to the regulatory effect of miR-15a. Our findings contribute to uncovering novel pathogenesis for ischemic brain injury.

Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification.

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies. Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation. Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis in FLT3/ITD-positive leukemia cells. Mechanistically, melatonin preferentially causes overproduction of reactive oxygen species (ROS) and ultimately massive cell death in FLT3-ITD AML cells. Moreover, melatonin significantly enhances the cytotoxicity induced by the FLT3 tyrosine kinase inhibitor sorafenib in AML cells with FLT3/ITD through redox modification. Importantly, combination of melatonin and sorafenib exhibited highly synergistic therapeutic activity in MV4-11 xenografts and a murine model bearing FLT3/ITD leukemia. Conclusion: This study indicates that melatonin, alone or in combination with sorafenib, has potential to improve the therapeutic outcome of AML patients with FLT3-ITD mutation that merits further investigation.