Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

The MADS-box gene RhAGL6 plays a master role in regulating the receptacle malformation in rose at low temperature

Low temperature usually results in the developmental deformity of flower organs,immensely affecting the quality of rose flowers.However,it's largely unknown about the regulatory mechanisms activated by low temperature.Here,we used a low temperature-sensitive Rosa hybrida cv.‘Peach Avalanche’to screen a MADS-box gene RhAGL6 via conjoint analysis between RNA sequencing(RNA-seq)and whole-genome bisulfite sequencing(WGBS).Furthermore,we found that low temperature induced the hypermethylation and elevated histone 3 lys-27 trimethylation(H3K27me3)level on the RhAGL6 promoter,leading to decreased RhAGL6 expression.In addition,RhAGL6 silencing resulted in the formation of abnormal receptacles.We also found that the levels of gibberellins(GA3)and abscisic acid(ABA)in the receptacle under low temperature were lower and higher,respectively,than under normal temperature.Promoter activity analysis revealed that GA3 significantly activated RhAGL6 promoter activity,whereas ABA inhibited it.Thus,we propose that RhAGL6 regulates rose receptacle development by integrating epigenetic regulation and phytohormones signaling at low temperature.

Aquaporin,beyond a transporter

Aquaporins(AQPs)are one of the most ancient superfamily proteins,which are essential for maintaining the fluid homeostasis of most organisms against various environments.Here,the latest findings for function of AQPs in cell signal transduction in plants are summarized.We also put forward several issues that still need to be addressed in the future.

Influence of Bayer Red Mud on the Operational and Mechanical Characteristics of Composite Cement Mortar

The aim of this study is to enhance the value and utilization of red mud generated in the Bayer process by preparing composite cement mortars.The effects of two different types of Bayer red mud with varying physical and chemical characteristics on the fluidity,mechanical strength,mineral composition,and microstructure of the composite cement mortar were systematically evaluated.The results showed that the optimal addition of red mud A was 10 wt%,while it was 20 wt% for red mud B.The mechanical properties of the composite cement mortar met the standards for P·O42.5 cement.Furthermore,the composite mortar with the addition of red mud B showed higher flexural and compressive strengths compared to the composite mortar with red mud A.This improvement is attributed to the smaller particle size of red mud B,which filled the micro-pores and increased the compactness of the cement stone,as well as its higher content of Na_(2)O,K_(2)O,and other free alkalis,which resulted in more obvious alkali activation,accelerating the hydration of the active minerals in the slurry.

Optimal Design for an End Face Engagement Worm Gear with Multiple Worm-wheel Meshing

To solve the problem for lacking a special mechanical transmission that could provide multiple outputs with high transmission efficiency and good lubrication in the modem industrial, a novel worm gear, named end face engagement worm gear, with multiple worm-wheel meshing is proposed for the first time. The essential parameters for the worm gear are optimized to enhance lubrication and meshing properties. Moreover, analysis of variance（ANOVA） is applied to determine the optimum levels and to determine the influence of parameters. The ANOVA results show that the novel end face engagement worm gear with multiple worm wheels provides high lubrication（the lubrication angle is more than 89~） and meshing performance（the induce normal curvature is less than 0.0002 mm ＇）. The interaction between center distance and roller slant distance most strongly influences the lubrication angle（contributed 51.6%）, followed by the parameters of center distance（contributed 25.0%）, roller slant distance（contributed 16.4%）, tooth angle of gear, gear ratio, and roller radius. In addition, roller radius most strongly influences the induced normal curvature（contributed 39.4%）, followed by roller slant distance（contributed 15.2%）, tooth angle of the gear（contributed 9.0%）, center distance, and gear ratio. The proposed worm gear helps to enrich the no-backlash high precision worm drive and the optimal design method can provide a useful reference on performance improvement of other worm gear.

RhMYB108,an R2R3-MYB transcription factor,is involved in ethylene-and JA-induced petal senescence in rose plants

Rose(Rosa hybrida)plants are major ornamental species worldwide,and their commercial value greatly depends on their open flowers,as both the quality of fully open petals and long vase life are important.Petal senescence can be started and accelerated by various hormone signals,and ethylene is considered an accelerator of petal senescence in rose.To date,however,the underlying mechanism of signaling crosstalk between ethylene and other hormones such as JA in petal senescence remains largely unknown.Here,we isolated RhMYB108,an R2R3-MYB transcription factor,which is highly expressed in senescing petals as well as in petals treated with exogenous ethylene and JA.Applications of exogenous ethylene and JA markedly accelerated petal senescence,while the process was delayed in response to applications of 1-MCP,an ethylene action inhibitor.In addition,silencing of RhMYB108 alter the expression of SAGs such as RhNAC029,RhNAC053,RhNAC092,RhSAG12,and RhSAG113,and finally block ethylene-and JA-induced petal senescence.Furthermore,RhMYB108 was identified to target the promoters of RhNAC053,RhNAC092,and RhSAG113.Our results reveal a model in which RhMYB108 functions as a receptor of ethylene and JA signals to modulate the onset of petal senescence by targeting and enhancing senescence-associated gene expression.

A new species of Ohirathous Han & Park(Coleoptera:Elateridae:Dendrometrinae) from China, with a key to Chinese species

Ohirathous emarginatus sp. nov. is described and illustrated from China. A key and a checklist of the known species in this genus, together with a distribution map of two Ohirathous species, are provided.

Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine?Autophagy regulation also works

Exploring the therapeutic effect of single atom catalysts beyond reactive oxygen species(ROS)modulation would boost the prosperity of nanomedicine in cancer treatment.Autophagy as a vital therapy target offers new options for the control of renal cell carcinoma(RCC)progression.Herein,Fe single atom-decorated graphene oxide(Fe_(1)-GO)nanosheet is developed to be a feasible autophagy inducer in RCC treatment.With the well-dispersed O-Fe_(1)-O active sites,Fe_(1)-GO kills ACHN cells effectively but maintains acceptable cytotoxicity to the normal podocyte and HK2 ones.In-depth analyses ascribe the inhibition of ACHN cells to the upregulated autophagy instead of the commonly known catalytic ROS generation.The in vivo therapeutic effect of Fe_(1)-GO nanomedicine is also validated by the RCC-bearing BALB/c mice model,realizing an 89% reduction of tumor weight and good biosafety.This work provides new insights into the design of autophagy regulators as well as potential therapeutic strategies for RCC treatment.

Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

Self-assembly synthesis of SnNb2O6/amino-functionalized graphene nanocomposite as high-rate anode materials for sodium-ion batteries

A two-dimensional(2 D)SnNb_(2)O_(6)/amino-functionalized graphene(En-RGO)nanocomposite with a representative 2 D-2 D architecture has been constructed by an easy self-assembly approach and firstly investigated as anode materials for secondary sodium-ion batteries.The SnNb_(2)O_(6)nanosheets are evenly anchored with the aminofunctionalized graphene through electrostatic attractive interplay between the negatively charged SnNb_(2)O_(6)and positively charged En-RGO after modification.As a result,a remarkable reversible capacity of 300 mAh·g^(-1)was obtained at 50 mA·g^(-1),and significantly,the En-RGO electrode could also deliver ultra-long calendar life up to1900 cycles with a high reversible capacity of200 mAh·g^(-1)at current of 500 mA·g^(-1).Such excellent electrochemical characteristics can be mainly ascribed to its fast pseudo-capacitive energy storage mechanism,and the capacitive contribution can even reach up to 90%at1.2 mV·s^(-1).

Plasticity of mycangia in Xylosandrus ambrosia beetles

Insects that depend on microbial mutualists evolved a variety of organs to transport the microsymbionts while dispersing. The ontogeny and variability of such organs is rarely studied, and the microsymbiont*s effects on the animal tissue development remain unknown in most cases. Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae or Platypodinae) and their mutualistic fungi are an ideal system to study the animalfungus interactions. While the interspecific diversity of their fungus transport organ一 mycangia—is well-known, their developmental plasticity has been poorly described. To determine the ontogeny of the mycangium and the influence of the symbiotic fungus on the tissue development, we dissected by hand or scanned with micro-CT the mycangia in various developmental stages in five Xylosandrus ambrosia beetle species that possess a large, mesonotal mycangium: Xylosandrus amputatus. Xylosandrus compactus, Xylosandrus crassiusculus, Xylosandrus discolor, and Xylosandrus germanus. We processed 181 beetle samples from the United States and China. All five species displayed three stages of the mycangium development:(1) young teneral adults had an empty, deflated and cryptic mycangium without fungal mass;(2) in fully mature adults during dispersal, the promesonotal membrane was inflated, and most individuals developed a mycangium mostly filled with the symbiont, though size and symmetry varied;and (3) after successful establishment of their new galleries, most females discharged the bulk of the fun gal inoculum and deflated the mycangium. Experimental aposymbiotic individuals demonstrated that the pronotal membrane invaginated independently of the presence of the fungus, but the fungus was required for inflation. Mycangia are more dynamic than previously thought, and their morphological changes correspond to the phases of the symbiosis. Importantly, studies of the fungal symbionts or plant pathogen transmission in ambrosia beetles need to consider which developmental stage to sample. We provide illustrations of the different stages, including microphotography of dissections and micro-CT scans.