Soluble humic acid suppresses plant immunity and ethylene to promote soybean nodulation.

Symbiotic nitrogen fixation (SNF) is a crucial process for nitrogen geochemical cycling and plant-microbe interactions. Water-soluble humic acid (WSHM), an active component of soil humus, has been shown to promote SNF in the legume-rhizobial symbiosis, but its molecular mechanism remains largely unknown. To reveal the SNF-promoting mechanism, we conducted transcriptomic analysis on soybean treated with WSHM. Our findings revealed that up- and downregulated differentially expressed genes (DEGs) were mainly involved in plant cell-wall/membrane formation and plant defence/immunity in the early stage, while the late stage was marked by the flavonoid synthesis and ethylene biosynthetic process. Further study on representative DEGs showed that WSHM could inhibit GmBAK1d-mediated immunity and BR signalling, thereby promoting rhizobial colonisation, infection, and nodulation, while not favoring pathogenic bacteria colonisation on the host plant. Additionally, we also found that the ethylene pathway is necessary for promoting the soybean nodulation by WSHM. This study not only provides a significant advance in our understanding of the molecular mechanism of WSHM in promoting SNF, but also provides evidence of the beneficial interactions among the biostimulator, host plant, and soil microbes, which have not been previously reported.

DEG 15, an update of the Database of Essential Genes that includes built-in analysis tools.

Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes (www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.

Unraveling the Diverse Roles of Neglected Genes Containing Domains of Unknown Function (DUFs): Progress and Perspective.

Domain of unknown function (DUF) is a general term for many uncharacterized domains with two distinct features: relatively conservative amino acid sequence and unknown function of the domain. In the Pfam 35.0 database, 4795 (24%) gene families belong to the DUF type, yet, their functions remain to be explored. This review summarizes the characteristics of the DUF protein families and their functions in regulating plant growth and development, generating responses to biotic and abiotic stress, and other regulatory roles in plant life. Though very limited information is available about these proteins yet, by taking advantage of emerging omics and bioinformatic tools, functional studies of DUF proteins could be utilized in future molecular studies.

Room temperature fabrication of magnetic covalent organic frameworks for analyzing sulfonamide residues in animal-derived foods.

A magnetic solid phase extraction method based on magnetic covalent organic frameworks (TpBD@Fe3 O4 ; 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD)) combined with high performance liquid chromatography has been developed to detect the sulfonamides including sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole in milk and meat. TpBD@Fe3 O4 were synthesized at room temperature under mild reaction conditions with a simple and rapid operation. The TpBD@Fe3 O4 exhibited higher extraction efficiency because of the π-π and electrostatic interactions between the benzene ring structure of the TpBD and the sulfonamide molecules. The extraction conditions including the dosage of adsorbents, the type and dosage of eluent, the elution time, and the pH of the sample solution were fully optimized. The detection results showed good linearity over a wide range (50-5 × 104 ng/mL) and low detection limits (3.39-5.77 ng/mL) for the sulfonamide targets. The practicability of this magnetic solidphase extraction-high-performance liquid chromatography method was further evaluated by analyzing milk and meat samples, with recoveries of the targets of 71.6-110.8% in milk and 71.9-109.7% in pork. The successful detection of sulfonamides residues has demonstrated the TpBD@Fe3 O4 excellent practical potential for analyzing pharmaceutical residues in animal-derived foods.

Diphenyl diselenide protects motor neurons through inhibition of microglia-mediated inflammatory injury in amyotrophic lateral sclerosis.

Microglia-mediated neuroinflammatory response and neuron damage are considered as a self-propelling progressive cycle, being strongly implicated in the progression of neurodegeneration in amyotrophic lateral sclerosis (ALS). Diphenyl diselenide (DPDS), a simple organoselenium compound, has been known to possess multiple pharmacological properties. The purpose of this study was to explore the neuroprotective effects of DPDS against microglia-mediated neuroinflammatory injury in ALS models. We found that DPDS pretreatment inhibited LPS-induced activation of IκB/NF-κB pathway and subsequent release of proinflammatory factors from activated primary hSOD1G93A microglia. Moreover, DPDS suppressed NLRP3 inflammasome activation by decreasing protein nitration via reduction in NO and ROS levels, whose low levels are related to NF-κB inhibition responsible for iNOS and NOX2 down-regulations, respectively. Notably, DPDS-mediated ROS attenuation was not linked to Nrf2 activation in this cellular model. Furthermore, in the absence of activated microglia, DPDS has no significant effect on the individual hSOD1G93A-NSC34 cells; however, in in vitro neuron-microglia conditional culture and co-culture experiments, DPDS protected motor neurons from neurotoxic damage caused by LPS or BzATP-stimulated microglia activation. Above observations suggest that DPDS-afforded neuroprotection is linked to inhibition of microglia-mediated neuroinflammation in ALS, which was further verified in vivo as shown by improvements of motor deficits, prolonged survival, and reduction of motor neuron loss and reactive microgliosis in hSOD1G93A transgenic mouse. Altogether, our results show that DPDS elicited neuroprotection in ALS models through inactivation of microglia by inhibiting IκB/NF-κB pathway and NLRP3 inflammasome activation, suggesting that DPDS may be a promising candidate for potential therapy for ALS.

Carbon dots derived from kanamycin sulfate with antibacterial activity and selectivity for Cr6+ detection.

Among antibacterial nanomaterials, carbon dots (CDs) have attracted much attention because of their unique physical and chemical properties and good biosafety. In this study, kanamycin sulfate (Kan), a broad-spectrum antibiotic, was used to synthesize novel carbon dots (CDs-Kan) by a one-step hydrothermal method. CDs-Kan showed good inhibitory effects on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Further, scanning electron microscopy revealed that treatment with CDs-Kan and Kan resulted in the same phenomena. In particular, the morphologies of S. aureus cells treated with CDs-Kan and Kan became smaller and irregular, whereas the surfaces of E. coli cells protruded and formed vesicles. These results indicated that CDs-Kan was shown to retain the good antibacterial activity of Kan as well as its main bactericidal functional groups, namely, the amino sugar and amino cyclic alcohol, We refer to this phenomenon as the "preservation property". We also found that CDs-Kan has good biocompatibility and nontoxic properties. Moreover, CDs-Kan was successfully applied to the biological imaging of fungi and plant cells. In addition, CDs-Kan could be used as a fluorescent probe for the quick, sensitive, and selective detection of Cr6+. Therefore, CDs-Kan not only retained the good bacteriostatic properties of Kan but also expanded its application in bioimaging and biosensors.

Serratia marcescens-derived fluorescent carbon dots as a platform toward multi-mode bioimaging and detection of p-nitrophenol.

Carbon dots (CDs) have excellent application prospects in various fields such as fluorescent dyes, but expanding their application, especially in bioimaging and the detection of organic pollutants, is still a major research objective. In this study, fluorescent CDs were successfully synthesized via the hydrothermal method using Serratia marcescens KMR-3. The platform based on CDs-KMR3 exhibited excellent stability, good biocompatibility, and low biotoxicity, and can be effectively applied to the imaging of bacteria, fungi, plant cells, protozoa and mammalian cells, and can specifically stain the membranes of all tested cells. In this study, for the first time, bacteria-derived CDs were used to image the representative species of organisms ranging from lower-order to higher-order organisms, thereby proving the feasibility of the application of CDs in the fluorescence imaging of Paramecium caudatum. Additionally, CDs-KMR3 can rapidly diffuse into all the parts of the leaf through diffusion into the veins and intercellular interstitium in response to the induction of transpiration. Moreover, the data illustrate that CDs-KMR3 are likely to enter the digestive tracts of microworms by ingestion through the oral cavity and pharynx, and spread to the pseudocoelom and somatic cells, and finally to be excreted from microworms through the anus. Furthermore, this platform can be utilized as fluorescent probes for the rapid and highly selective detection of p-nitrophenol (p-NP). Moreover, this study contributed to the increased application of bacteria-derived CDs in bioimaging and detection of p-NP.

Novel fluorescent nitrogen-doped carbon dots derived from Panax notoginseng for bioimaging and high selectivity detection of Cr6.

Carbon dots (CDs) and photoluminescent carbon dots (Pn-CDs) are promising nanomaterials due to their bioimaging applications and have attracted considerable attention because of their excellent stability, good biocompatibility, and low biotoxicity. Here, the Pn-CDs and highly fluorescent nitrogen-doped CDs (Pn N-CDs) derived from Panax notoginseng were successfully synthesized by a simple hydrothermal method. Pn N-CDs exhibit optical properties and stability superior to those of Pn-CDs and can be better used as fluorescent dyes and probes in biological imaging. The obtained Pn N-CDs can be effectively applied to the imaging of bacteria, fungi, plant cells, and protozoa. In addition, Pn N-CDs can perform specific staining on the membranes of all tested cells. The in vivo imaging of mice revealed that Pn N-CDs exhibit nontoxicity and good biocompatibility and biodistribution. Furthermore, Pn N-CDs can be utilized as fluorescent probes for the rapid and highly selective detection of Cr6+. Hence, a simple, cost-effective, scalable, and green synthetic approach based on traditional Chinese medicine-derived CDs can be used to develop biolabeling, membrane targeting, and optical sensing probes.

Wild-type p53-induced phosphatase 1 down-regulation promotes apoptosis by activating the DNA damage-response pathway in amyotrophic lateral sclerosis.

Accumulation of DNA damage has been detected in the spinal cord of patients as well as in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that terminates DNA-damage responses via dephosphorylation of DNA-damage response proteins, namely ataxia-telangiectasia mutated (ATM) kinase, checkpoint kinase 2, and p53, thus enhancing cell proliferation. However, the role of Wip1, DNA-damage responses, and their interaction in ALS development remains to be elucidated. Here, we showed that Wip1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro. The DNA-damage response was activated in superoxide dismutase 1 (SOD1) G93A-transfected cells. However, increased expression of Wip1 improved cell viability and inhibited the DNA-damage response in mutated SOD1G93A cells. Further studies demonstrated that decreased Wip1 expression reduced cell viability and further activated the DNA-damage response in chronic H2O2-treated NSC34 cells. In contrast, Wip1 promoted cell survival and suppressed DNA damage-induced apoptosis during persistent DNA damage conditions. Over-expression of Wip1 in the central nervous system (CNS) can delay the onset of disease symptoms, extended the survival, decreased MN loss improved motor function and inhibit the DNA-damage response in SOD1 G93A mice. Furthermore, homeodomain-interacting protein kinase 2 (HIPK2) promoted the degradation of Wip1 via the ubiquitin-proteasome system during chronic stress. These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS. Wip1 may play a protective role by targeting the DNA-damage response in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS.

Lithium facilitates removal of misfolded proteins and attenuated faulty interaction between mutant SOD1 and p-CREB (Ser133) through enhanced autophagy in mutant hSOD1G93A transfected neuronal cell lines.

Abnormally protein aggregation and deposition are key pathological features of ALS, which may related with dysfunctional cellular autophagy. In the current study, we found that, compared with wtSOD1 cells, serum starvation treatment resulted in significant higher percentage of apoptosis in mutSOD1 cells; Lithium treatment exerted protection for those mutSOD1 cells, with decreased GFP-tagged mutant SOD1 protein aggregates deposition; Whereas, pre-treatment with Baf or 3-MA (autophagy inhibitors) blocked protection of lithium for mutant SOD1 cells, and induced increased GFP-tagged mutant SOD1 protein aggregation. Further, Western blots results showed that lithium treatment led to decrease of mutant hSOD1 protein levels in both Triton X-100 soluble and Triton X-100 insoluble fraction of mutSOD1 cells. Besides, improper binding of mutant SOD1 proteins' aggregates with p-CREB (Ser133) (transcription factor) in mutSOD1 cells were demonstrated; whereas lithium treatment attenuated this fault interaction. In conclusion, our results showed that, in mutSOD1 cells, mutSOD1 protein aggregates were related with abnormal autophagic regulation. Lithium treatment could induce autophagy and enhance clearance of protein aggregates, further exerting protection on mutSOD1 cells. More importantly, we uncovered another distinct pathological role of mutSOD1 protein aggregates, that is abnormal binding with p-CREB (Ser133), an important transcription factor, which may play crucial role in the PI3K-Akt-CREB-AEG-1 signaling pathway.

Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1G93A mutation.

AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.

Pollution haven or porter? The impact of environmental regulation on location choices of pollution-intensive firms in China.

Using firm establishment-level data combined with provincial socio-economic characteristic panel data in China for the period of 2011-2015, this study seeks to empirically examine the impact of environmental regulation on location choices of polluting firms. The results of the conditional logit model provide compelling evidence that environmental regulations do affect the location choice of firms in polluting industries. Instead of supporting the pollution haven effect, our results consistently confirm the Porter effect at the country level. This result is robust when taking endogeneity problem into account, adopting various model specifications and estimation strategies, using alternative measurements of environmental regulation and location choices, and subsampling excluding international political events. However, the results also show divergent effect of environmental regulation on location choices for heterogeneous firms. Specifically, polluting firms in eastern region prefer to invest in provinces with stringent environmental policies but those in other regions, especially in northeastern region, choose to locate in provinces with lax environmental regulation. While water-dependent polluting firms with a low level of footlooseness are more likely to enter locations with loose environmental regulation, air pollution-intensive firms tend to locate in provinces with tight environmental legislation. These results have policy implications for transitional China as well as other developing countries with similar experience.

DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements.

The combination of high-density transposon-mediated mutagenesis and high-throughput sequencing has led to significant advancements in research on essential genes, resulting in a dramatic increase in the number of identified prokaryotic essential genes under diverse conditions and a revised essential-gene concept that includes all essential genomic elements, rather than focusing on protein-coding genes only. DEG 10, a new release of the Database of Essential Genes (available at http://www.essentialgene.org), has been developed to accommodate these quantitative and qualitative advancements. In addition to increasing the number of bacterial and archaeal essential genes determined by genome-wide gene essentiality screens, DEG 10 also harbors essential noncoding RNAs, promoters, regulatory sequences and replication origins. These essential genomic elements are determined not only in vitro, but also in vivo, under diverse conditions including those for survival, pathogenesis and antibiotic resistance. We have developed customizable BLAST tools that allow users to perform species- and experiment-specific BLAST searches for a single gene, a list of genes, annotated or unannotated genomes. Therefore, DEG 10 includes essential genomic elements under different conditions in three domains of life, with customizable BLAST tools.

Downregulation of Homer1b/c in SOD1 G93A Models of ALS: A Novel Mechanism of Neuroprotective Effect of Lithium and Valproic Acid.

BACKGROUND: Mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms have not been elucidated yet. Homer family protein Homer1b/c is expressed widely in the central nervous system and plays important roles in neurological diseases. In this study, we explored whether Homer1b/c was involved in SOD1 mutation-linked ALS. RESULTS: In vitro studies showed that the SOD1 G93A mutation induced an increase of Homer1b/c expression at both the mRNA and protein levels in NSC34 cells. Knockdown of Homer1b/c expression using its short interfering RNA (siRNA) (si-Homer1) protected SOD1 G93A NSC34 cells from apoptosis. The expressions of Homer1b/c and apoptosis-related protein Bax were also suppressed, while Bcl-2 was increased by lithium and valproic acid (VPA) in SOD1 G93A NSC34 cells. In vivo, both the mRNA and protein levels of Homer1b/c were increased significantly in the lumbar spinal cord in SOD1 G93A transgenic mice compared with wild type (WT) mice. Moreover, lithium and VPA treatment suppressed the expression of Homer1b/c in SOD1 G93A mice. CONCLUSION: The suppression of SOD1 G93A mutation-induced Homer1b/c upregulation protected ALS against neuronal apoptosis, which is a novel mechanism of the neuroprotective effect of lithium and VPA. This study provides new insights into pathogenesis and treatment of ALS.

Differential response in levels of high-density lipoprotein cholesterol to one-year metformin treatment in prediabetic patients by race/ethnicity.

BACKGROUND: As a first-line diabetes drug that is widely prescribed around the world, metformin has been demonstrated to be effective in reducing microvascular risk, in addition to lowering glucose levels. Specifically, metformin use has been shown to be associated with improved lipid profiles, such as increased levels of high-density lipoprotein cholesterol (HDL-C). However, no study has been performed to examine the differential response in HDL-C levels to metformin treatment by race/ethnicity. METHODS: Here, based on a re-analysis of the data from the Diabetes Prevention Program, which involved pre-diabetic participants receiving 850 mg of metformin twice daily, we compared the lipid profile changes following the metformin use. The participants were composed of 602 Whites, 221 African Americans (AAs) and 162 Hispanics. RESULTS: We found that the one-year metformin treatment resulted in a significant increase in HDL-C levels in Whites (p = 0.002) and AAs (p = 0.016), but not in Hispanics. Consistently, both Whites (p = 0.018) and AAs (p = 0.020) had more pronounced changes in HDL-C levels than Hispanics following metformin treatment. CONCLUSION: This result suggests a notion that Whites and AAs are more responsive than Hispanics to one-year metformin use in HDL-C level changes, and that racial and ethnic identity is a factor to consider when interpreting the effects of metformin treatment on lipid profiles.

DoriC 5.0: an updated database of oriC regions in both bacterial and archaeal genomes.

Replication of chromosomes is one of the central events in the cell cycle. Chromosome replication begins at specific sites, called origins of replication (oriCs), for all three domains of life. However, the origins of replication still remain unknown in a considerably large number of bacterial and archaeal genomes completely sequenced so far. The availability of increasing complete bacterial and archaeal genomes has created challenges and opportunities for identification of their oriCs in silico, as well as in vivo. Based on the Z-curve theory, we have developed a web-based system Ori-Finder to predict oriCs in bacterial genomes with high accuracy and reliability by taking advantage of comparative genomics, and the predicted oriC regions have been organized into an online database DoriC, which is publicly available at http://tubic.tju.edu.cn/doric/ since 2007. Five years after we constructed DoriC, the database has significant advances over the number of bacterial genomes, increasing about 4-fold. Additionally, oriC regions in archaeal genomes identified by in vivo experiments, as well as in silico analyses, have also been added to the database. Consequently, the latest release of DoriC contains oriCs for >1500 bacterial genomes and 81 archaeal genomes, respectively.

FRK suppresses the proliferation of human glioma cells by inhibiting cyclin D1 nuclear accumulation.

The Fyn related kinase (FRK) is a noteworthy member of the Src non-receptor tyrosine kinase family for its distinctive tumor suppressive function. Recently, we have shown that FRK plays a protective role against the progression of glioma by suppressing cell migration and invasion. However, it is unclear whether the cell growth of glioma is also regulated by FRK and by which mechanism FRK alters its specific biological functions. In the current study, we found that FRK over-expression significantly suppressed the proliferation of glioma cells. In contrast, FRK knockdown by siRNA promoted glioma cell growth. In addition, FRK over-expression caused G1 phase arrest as well as apoptosis of glioma cells. Further investigation disclosed that FRK-induced G1 arrest was accompanied by down-regulation of hyperphosphorylated retinoblastoma protein (pRb), which led to the consequent suppression of E2F1. More importantly, we found that over-expression of FRK inhibited proper cyclin D1 accumulation in the nucleus of proliferating cells. Taken together, our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells.

A Brief Review: The Z-curve Theory and its Application in Genome Analysis.

In theoretical physics, there exist two basic mathematical approaches, algebraic and geometrical methods, which, in most cases, are complementary. In the area of genome sequence analysis, however, algebraic approaches have been widely used, while geometrical approaches have been less explored for a long time. The Z-curve theory is a geometrical approach to genome analysis. The Z-curve is a three-dimensional curve that represents a given DNA sequence in the sense that each can be uniquely reconstructed given the other. The Z-curve, therefore, contains all the information that the corresponding DNA sequence carries. The analysis of a DNA sequence can then be performed through studying the corresponding Z-curve. The Z-curve method has found applications in a wide range of areas in the past two decades, including the identifications of protein-coding genes, replication origins, horizontally-transferred genomic islands, promoters, translational start sides and isochores, as well as studies on phylogenetics, genome visualization and comparative genomics. Here, we review the progress of Z-curve studies from aspects of both theory and applications in genome analysis.

Comparative Morpho-Physiological, Biochemical, and Gene Expressional Analyses Uncover Mechanisms of Waterlogging Tolerance in Two Soybean Introgression Lines.

Waterlogging is one of the key abiotic factors that severely impedes the growth and productivity of soybeans on a global scale. To develop soybean cultivars that are tolerant to waterlogging, it is a prerequisite to unravel the mechanisms governing soybean responses to waterlogging. Hence, we explored the morphological, physiological, biochemical, and transcriptional changes in two contrasting soybean introgression lines, A192 (waterlogging tolerant, WT) and A186 (waterlogging sensitive, WS), under waterlogging. In comparison to the WT line, waterlogging drastically decreased the root length (RL), shoot length (ShL), root fresh weight (RFW), shoot fresh weight (ShFW), root dry weight (RDW), and shoot dry weight (ShDW) of the WS line. Similarly, waterlogging inhibited soybean plant growth by suppressing the plant's photosynthetic capacity, enhancing oxidative damage from reactive oxygen species, and decreasing the chlorophyll content in the WS line but not in the WT line. To counteract the oxidative damage and lipid peroxidation, the WT line exhibited increased activity of antioxidant enzymes such as peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), as well as higher levels of proline content than the WS line. In addition, the expression of antioxidant enzyme genes (POD1, POD2, FeSOD, Cu/ZnSOD, CAT1, and CAT2) and ethylene-related genes (such as ACO1, ACO2, ACS1, and ACS2) were found to be up-regulated in WT line under waterlogging stress conditions. In contrast, these genes showed a down-regulation in their expression levels in the stressed WS line. The integration of morpho-physiological, biochemical, and gene expression analyses provide a comprehensive understanding of the responses of WT and WS lines to waterlogging conditions. These findings would be beneficial for the future development of soybean cultivars that can withstand waterlogging.

Roflupram alleviates autophagy defects and reduces mutant hSOD1-induced motor neuron damage in cell and mouse models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease involving motor neuron (MN) degeneration and is characterized by ongoing myasthenia and amyotrophia in adults. Most ALS patients die of respiratory muscle paralysis after an average of 3-5 years. Defective autophagy in MNs is considered an important trigger of ALS pathogenesis. Roflupram (ROF) was demonstrated to activate autophagy in microglial cells and exert protective effects against Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, our research aimed to investigate the efficacy and mechanism of ROF in treating ALS both in vivo and in vitro. We found that ROF could delay disease onset and prolong the survival of hSOD1-G93A transgenic mice. Moreover, ROF protected MNs in the anterior horn of the spinal cord, activated the AMPK/ULK1 signaling pathway, increased autophagic flow, and reduced SOD1 aggregation. In an NSC34 cell line stably transfected with hSOD1-G93A, ROF protected against cellular damage caused by hSOD1-G93A. Moreover, we have demonstrated that ROF inhibited gliosis in ALS model mice. Collectively, our study suggested that ROF is neuroprotective in ALS models and the AMPK/ULK1 signaling pathway is a potential therapeutic target in ALS, which increases autophagic flow and reduces SOD1 aggregation.