Plasma-activated water: Candidate hand disinfectant for SARS-CoV-2 transmission disruption.

The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20 % (±2.88 %), 46.24 % (±1.79 %), and 91.71 % (±0.47 %), respectively. Additionally, determination of PAW's physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.

Green light mediates atypical photomorphogenesis by dual modulation of Arabidopsis phytochromes B and A.

Although green light (GL) is located in the middle of the visible light spectrum and regulates a series of plant developmental processes, the mechanism by which it regulates seedling development is largely unknown. In this study, we demonstrated that GL promotes atypical photomorphogenesis in Arabidopsis thaliana via the dual regulations of phytochrome B (phyB) and phyA. Although the Pr-to-Pfr conversion rates of phyB and phyA under GL were lower than those under red light (RL) in a fluence rate-dependent and time-dependent manner, long-term treatment with GL induced high Pfr/Pr ratios of phyB and phyA. Moreover, GL induced the formation of numerous small phyB photobodies in the nucleus, resulting in atypical photomorphogenesis, with smaller cotyledon opening angles and longer hypocotyls in seedlings compared to RL. The abundance of phyA significantly decreased after short- and long-term GL treatments. We determined that four major PHYTOCHROME-INTERACTING FACTORs (PIFs: PIF1, PIF3, PIF4, and PIF5) act downstream of phyB in GL-mediated cotyledon opening. In addition, GL plays opposite roles in regulating different PIFs. For example, under continuous GL, the protein levels of all PIFs decreased, whereas the transcript levels of PIF4 and PIF5 strongly increased compared with dark treatment. Taken together, our work provides a detailed molecular framework for understanding the role of the antagonistic regulations of phyB and phyA in GL-mediated atypical photomorphogenesis.

L-Theanine Prolongs the Lifespan by Activating Multiple Molecular Pathways in Ultraviolet C-Exposed Caenorhabditis elegans.

L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases.

Agrobacterium rhizogenes-mediated marker-free transformation and gene editing system revealed that AeCBL3 mediates the formation of calcium oxalate crystal in kiwifruit.

The transformation and gene editing of the woody species kiwifruit are difficult and time-consuming. The fast and marker-free genetic modification system for kiwifruit has not been developed yet. Here, we establish a rapid and efficient marker-free transformation and gene editing system mediated by Agrobacterium rhizogenes for kiwifruit. Moreover, a removing-root-tip method was developed to significantly increase the regeneration efficiency of transgenic hairy roots. Through A. rhizogenes-mediated CRISPR/Cas9 gene editing, the editing efficiencies of CEN4 and AeCBL3 achieved 55 and 50%, respectively. And several homozygous knockout lines for both genes were obtained. Our method has been successfully applied in the transformation of two different species of kiwifruit (Actinidia chinensis 'Hongyang' and A.eriantha 'White'). Next, we used the method to study the formation of calcium oxalate (CaOx) crystals in kiwifruit. To date, little is known about how CaOx crystal is formed in plants. Our results indicated that AeCBL3 overexpression enhanced CaOx crystal formation, but its knockout via CRISPR/Cas9 significantly impaired crystal formation in kiwifruit. Together, we developed a fast maker-free transformation and highly efficient CRISPR-Cas9 gene editing system for kiwifruit. Moreover, our work revealed a novel gene mediating CaOx crystal formation and provided a clue to elaborate the underlying mechanisms.

Investigation into the communication between unheated and heat-stressed Caenorhabditis elegans via volatile stress signals.

Our research group has recently found that radiation-induced airborne stress signals can be used for communication among Caenorhabditis elegans (C. elegans). This paper addresses the question of whether heat stress can also induce the emission of airborne stress signals to alert neighboring C. elegans and elicit their subsequent stress response. Here, we report that heat-stressed C. elegans produces volatile stress signals that trigger an increase in radiation resistance in neighboring unheated C. elegans. When several loss-of-function mutations affecting thermosensory neuron (AFD), heat shock factor-1, HSP-4, and small heat-shock proteins were used to test heat-stressed C. elegans, we found that the production of volatile stress signals was blocked, demonstrating that the heat shock response and ER pathway are involved in controlling the production of volatile stress signals. Our data further indicated that mutations affecting the DNA damage response (DDR) also inhibited the increase in radiation resistance in neighboring unheated C. elegans that might have received volatile stress signals, indicating that the DDR might contribute to radioadaptive responses induction by volatile stress signals. In addition, the regulatory pattern of signal production and action was preliminarily clarified. Together, the results of this study demonstrated that heat-stressed nematodes communicate with unheated nematodes via volatile stress signals.

Effects of non-thermal atmospheric plasma on protein.

Currently, the advancement in non-thermal atmospheric plasma technology enables plasma treatments on some heat-sensitive targets, including biological substances, without unspecific damage caused by thermal effect. The significant effects of non-thermal atmospheric plasma modulating biological events have been demonstrated by considerable studies. Protein, one of the most important biomolecules, participates in the majority of the life-sustaining activities in all organisms, whose functions are derived from the diverse biochemical properties of amino acid compositions and four-tiered protein structure hierarchy. Therefore, the knowledge of how non-thermal atmospheric plasma affects protein greatly benefits the understanding and application of the non-thermal atmospheric plasma's effect in biological area. In this review, we summarize recent research progress on the effects of non-thermal atmospheric plasma, particularly its reactive species, on biochemical and biophysical characteristics of proteins at different structural levels that leads to their functional changes. Moreover, the physiological effects of non-thermal atmospheric plasma at cellular or organism level driven by the manipulations on protein and their relative application prospects are reviewed. Despite the exceptional application potential, the exploration of the non-thermal atmospheric plasma's effect on protein still confronts with difficulties due to the limited knowledge of the underlying mechanisms and the complexity of non-thermal atmospheric plasma operation systems, which requires further studies and standardization of non-thermal atmospheric plasma treatments.

Glutathione-depletion reinforced enzyme catalytic activity for photothermal assisted bacterial killing by hollow mesoporous CuO.

The emergence and prevalence of drug-resistant bacteria caused by the overuse of antibiotics pose new challenges to the treatment of bacterial infections. In this work, hollow mesoporous CuO nanozymes (HM-CuO nanozymes) as excellent antibacterial agents were prepared by a template method. The synthesized HM-CuO nanozymes exhibit peroxidase-like catalytic activity, which can efficiently catalyze H2O2 to generate toxic reactive oxygen species (ROS), causing fatal damage to bacteria. Moreover, the hyperthermia of HM-CuO produced by photothermal therapy (PTT) not only effectively kills bacteria but also enhances the catalytic activity of nanozymes and produces more ROS. Moreover, the HM-CuO nanozymes have a glutathione (GSH)-depleting function to effectively consume GSH in bacteria and generate Cu(I) with higher catalytic effect, which can significantly improve the sterilization effect and produce a 100% inhibitory rate against E. coli and S. aureus. Overall, the HM-CuO nanozymes with strong peroxidase-like catalytic activity, excellent photothermal performance and GSH consumption ability offer a promising synergistic strategy for clinical bacterial infection.

Digital Quantification Method for Sensitive Point-of-Care Detection of Salivary Uric Acid Using Smartphone-Assisted µPADs.

Uric acid (UA) is an important biomarker for many diseases. A sensitive point-of-care (POC) testing platform is designed for the digital quantification of salivary UA based on a colorimetric reaction on an easy-to-build smartphone-assisted microfluidic paper-based analytical device (SµPAD). UA levels are quantified according to the color intensity of Prussian blue on the SµPAD with the aid of a MATLAB code or a smartphone APP. A color correction method is specifically applied to exclude the light effect. Together with the engineering design of SµPADs, the background calibration function with the APP increases the UA sensitivity by 100-fold to reach 0.1 ppm with a linear range of 0.1-200 ppm. The assay time is less than 10 min. SµPADs demonstrate a correlation of 0.97 with a commercial UA kit for the detection of salivary UA in clinical samples. SµPADs provide a sensitive, fast, affordable, and reliable tool for the noninvasive POC quantification of salivary UA for early diagnosis of abnormal UA level-associated health conditions.

Evaluation of the Probiotic Potential of Lactobacillus delbrueckii ssp. indicus WDS-7 Isolated from Chinese Traditional Fermented Buffalo Milk In Vitro.

The present study aimed to evaluate the probiotic potential of lactic acid bacteria (LAB) isolated from Chinese traditional fermented buffalo milk. Out of 22 isolates, 11 were putatively identified as LAB preliminarily. A total of six LAB strains displayed strong adhesion to HT-29 cells and all these strains showed preferable tolerance to artificially simulated gastrointestinal juices. WDS-4, WDS-7, and WDS-18 exhibited excellent antioxidant capacities, including DPPH radical, ABTS+ radical, and superoxide anion scavenging activities. Compared with the other two LAB strains, WDS-7 had a stronger inhibition effect on four pathogens. Based on the 16S rRNA gene sequencing and phylogenetic analysis, WDS-7 was identified as Lactobacillus delbrueckii ssp. indicus and selected to assess the potential and safety of probiotics further. The results revealed that WDS-7 strain had a strong capacity for acid production and good thermal stability. WDS-7 strain also possessed bile salt hydrolase (BSH) activity. Compared to LGG, WDS-7 was a greater biofilm producer on the plastic surface and exhibited a better EPS production ability (1.94 mg/ml as a glucose equivalent). WDS-7 was proved to be sensitive in the majority of tested antibiotics and absence of hemolytic activity. Moreover, no production of biogenic amines and ß-glucuronidase was observed in WDS-7. The findings of this work indicated that L. delbrueckii ssp. indicus WDS-7 fulfilled the probiotic criteria in vitro and could be exploited for further evaluation in vivo.

Telmisartan ameliorates LPS-induced pneumonia in rats through regulation of the PPARγ/NF-κB pathway.

Pneumonia is a common disorder of the respiratory system associated with inflammation. Telmisartan (TEL) has been reported to treat inflammatory-related diseases. The current study aimed to investigate the possible role and action mechanism of telmisartan on lipopolysaccharide (LPS)-induced pneumonia in rats. Forty male Sprague Dawley rats aged 8 weeks were assigned into four groups ad libitum: a control group received saline only, an experimental group received LPS, a group received telmisartan (5 mg/kg), followed by LPS treatment, and a group received telmisartan (10 mg/kg), followed by LPS treatment. The LPS (2 mg/kg) and equal saline were administered intratracheally. Telmisartan was administered orally 5 days before LPS. After LPS treatment for 24 hr, bronchoalveolar lavage fluid (BALF) and serum were collected for the analysis of cell counts and/or cytokines. Lung tissues were used to perform histological examination, to assess oxidative stress levels, and to determine the levels of PPARγ/NF-κB pathway-related proteins. Rats that received LPS treatment exhibited high levels of lung wet/dry ratio, alkaline phosphatase, lactate dehydrogenase, BALF polymorphonuclear leukocytes count, inflammatory cytokines, and oxidative stress. Meanwhile, LPS also resulted in severe interstitial edema and inflammatory cell infiltration. Interestingly, telmisartan by oral administration markedly ameliorated the adverse effects of pneumonia in rats caused by LPS. In addition, western blotting further revealed that telmisartan could activate PPARγ and repress NF-κB (p65). Telmisartan is protective against pneumonia through inhibition of the inflammation and oxidative stress via the PPARγ/NF-κB pathway.

Atorvastatin regulates vascular smooth muscle cell phenotypic transformation by epigenetically modulating contractile proteins and mediating Akt/FOXO4 axis.

Atherosclerosis (AS) is a prevalent cardiovascular disease with severe morbidity and high mortality. Phenotypic regulation of vascular smooth muscle cells (VSMCs) from the contractile and quiescent phenotype to the synthetic type is a critical step for the vascular remodeling of AS. Atorvastatin, as a 3­hydroxy­3­methyl­glutaryl coenzyme A reductase inhibitor, presents an anti­inflammatory effect to improve vascular endothelial functions. The aim of the present study was to examine the effect of atorvastatin on VSMCs phenotypic transformation and the underlying mechanism. The rat primary VSMCs were isolated and identified. The protein expression of contractile proteins, such as α­SMA, SM­MHC, and SM22α, was reduced by angiotensin II (AngII) and enhanced by atorvastatin, in which atorvastatin could reverse the effect of AngII in the VSMCs. The treatment of HDAC inhibitor trichostatin A was able to enhance AngII­inhibited expression of α­SMA and SM­MHC. Atorvastatin regulated AngII­associated VSMCs phenotypic transformation by epigenetically regulating contractile proteins. Moreover, atorvastatin modulated platelet­derived growth factor­BB (PDGF­BB)­induced VSMC phenotypic transformation by modulating the Akt/forkhead Box O4 (FOXO4) axis. Immunofluorescence analysis revealed that PDGF­BB enhanced the accumulation of FOXO4 in the VSMCs, while the treatment of atorvastatin was able to attenuate this effect and the co­treatment of Akt inhibitor LY294002 could further inhibit the phenotype. The treatment of PDGF­BB enhanced the interaction of SRF with FOXO4 and myocardin in the VSMCs, in which the co­treatment of atorvastatin and LY294002 could reverse the effect of PDGF­BB in the system. Thus, atorvastatin regulates VSMCs phenotypic transformation by epigenetically modulating contractile proteins and mediating the Akt/FOXO4 axis. Findings of the present study provide new insights into the mechanism by which atorvastatin modulates VSMCs, providing valuable evidence for the application of atorvastatin in the treatment of AS.

In situ observation of mitochondrial biogenesis as the early event of apoptosis.

Mitochondrial biogenesis is a cell response to external stimuli which is generally believed to suppress apoptosis. However, during the process of apoptosis, whether mitochondrial biogenesis occurs in the early stage of the apoptotic cells remains unclear. To address this question, we constructed the COX8-EGFP-ACTIN-mCherry HeLa cells with recombinant fluorescent proteins respectively tagged on the nucleus and mitochondria and monitored the mitochondrial changes in the living cells exposed to gamma-ray radiation. Besides in situ detection of mitochondrial fluorescence changes, we also examined the cell viability, nuclear DNA damage, reactive oxygen species (ROS), mitochondrial superoxide, citrate synthase activity, ATP, cytoplasmic and mitochondrial calcium, mitochondrial mass, mitochondrial morphology, and protein expression related to mitochondrial biogenesis, as well as the apoptosis biomarkers. As a result, we confirmed that significant mitochondrial biogenesis took place preceding the radiation-induced apoptosis, and it was closely correlated with the apoptotic cells at late stage. The involved mechanism was also discussed.

Cold atmospheric plasma: A non-negligible strategy for viral RNA inactivation to prevent SARS-CoV-2 environmental transmission.

Cold atmospheric plasma (CAP), regarded as a powerful physics technology, displays antimicrobial, antitumor, and even antiviral properties, but the underlying mechanism is rarely studied. In this study, four CAP exposure doses (30, 60, 120, and 240 s) were applied to inactivate a severe acute respiratory syndrome coronavirus 2 like pseudovirus on a stainless steel disk, which comprised spike protein on its membrane and can express a green fluorescent protein. In order to unravel the potential effects of CAP irradiation on pseudovirus, infection assay, optical emission spectra analysis, transmission electron microscopy (TEM), sodium dodecyl sulfate polyacrylamide gel electrophoresis, ELISA, and qPCR experiments were carried out. As a result, our study indicated that CAP irradiation can significantly decrease the infectivity of pseudovirus in a dose dependent manner through destroying the cell membrane and further damaging viral RNA, with the molecular weight and conformation of spike receptor binding domain protein unchanged.

MicroRNA-22 regulates the proliferation, drug sensitivity and metastasis of human glioma cells by targeting SNAIL1.

The Editors of JBUON issue an Expression of Concern to 'MicroRNA-22 regulates the proliferation, drug sensitivity and metastasis of human glioma cells by targeting SNAIL1', by Yunqiang Zhang, Lijun Tu, Xiuhong Zhou, Bin Li; JBUON 2020;25(1):491-496; PMID: 32277674. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Xylooligosaccharides induce stomatal closure via salicylic acid signaling-regulated reactive oxygen species and nitric oxide production in Arabidopsis.

Xylooligosaccharides (XOS) are the major coproducts of biofuel production and the most representative functional sugar enhancing animal physiology. However, little is known regarding the biological relevance of XOS to plants. Here, we found XOS triggered stomatal closure in Arabidopsis in a dose-dependent manner. Pamarcological data showed that XOS-induced stomatal closure was markedly inhibited by catalase (CAT, a reactive oxygen species [ROS] scavenger), salicylhydroxamic acid (SHAM, a peroxidase inhibitor), and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, a nitric oxide [NO] scavenger). Moreover, XOS induced the production of ROS and NO in guard cells of Arabidopsis. ROS production was strongly restricted by CAT and SHAM, but was unaffected by treatment with diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor) or cPTIO. NO production was suppressed by CAT, SHAM, and cPTIO, but not by DPI. The elevation of ROS level mediated by SHAM-sensitive peroxidases occurred upstream of NO. Additionally, XOS-triggered stomatal closure and ROS and NO accumulation were significantly impaired in npr1 (salicylic acid signaling) mutant plants, but were not in jar1 (jasmonic acid signaling) or ein2 (ethylene signaling) mutant plants. Furthermore, XOS-induced stomatal closure was unaffected in both ost1 and atrbohD atrbohF (abscisic acid [ABA] signaling) mutant plants. Therefore, these results indicated that the biotic sugar, XOS, can elicit stomatal closure via salicylic acid signaling-mediated production of ROS and NO, in a manner independent of ABA signaling.

Theaflavin-regulated Imd condensates control Drosophila intestinal homeostasis and aging.

Black tea is the most widely consumed tea drink in the world and has consistently been reported to possess anti-aging benefits. However, whether theaflavins, one type of the characteristic phytochemicals in black tea extracts, are involved in regulating aging and lifespan in consumers remains largely unknown. In this study, we show that theaflavins play a beneficial role in preventing age-onset intestinal leakage and dysbiosis, thus delaying aging in Drosophila. Mechanistically, theaflavins regulate the condensate assembly of Imd to negatively govern the overactivation of Imd signals in fruit fly intestines. In addition, theaflavins prevent DSS-induced colitis in mice, suggesting theaflavins play a role in modulating intestinal integrity. Overall, our study reveals a molecular mechanism by which theaflavins regulate gut homeostasis likely through controlling Imd coalescence.

The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVES: Previously published systematic reviews have explored the effects of therapeutic hypothermia on adult patients with traumatic brain injury (TBI). However, none explored the effect of early prophylactic hypothermia (within 6 h from injury to hypothermia induction). Animal studies indicated that early prophylactic hypothermia may reduce secondary injury and improve neurological outcomes. This systematic review aimed to investigate the effects of early prophylactic hypothermia on adult TBI regarding mortality, favourable outcomes, and complications. DATA SOURCE: We searched electronic databases including Cochrane CENTRAL, PubMed, MEDLINE, CINAHL, EMBASE, Web of Science, OpenGrey, and ClinicalTrials.gov from inception to June 12, 2019. Manual search was conducted for additional information. REVIEW METHODS: Only randomised controlled trials were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the quality of included studies. We extracted general demographic characteristics, the initiation timing, methods of cooling, duration, target temperature, rewarming rate, mortality, neurological outcomes, and complications. RESULTS: Six studies with a total of 1207 participants were included. Meta-analyses showed no significant difference in mortality and favourable outcomes (risk ratio = 1.11, 95% confidence interval = 0.90-1.37, P = 0.32; risk ratio = 1.03, 95% confidence interval = 0.91-1.16, P = 0.65, respectively). Similar results were found regarding different durations of hypothermia and different rewarming rates. Various complications were reported in the included studies. No statistical difference was found in three studies, while complications were reported to be significantly higher in the hypothermia group in the other three studies. CONCLUSIONS: This review does not support the use of early prophylactic hypothermia (within 6 h after injury) as a neurological protection strategy in adult patients with TBI, irrespective of the short term or long term. No significant benefits were found regarding hypothermia with different rewarming rates. Owing to the limited number of studies, more randomised controlled trials with higher quality are required to establish true effects of early hypothermia in adult TBI.

The Arabidopsis small G-protein AtRAN1 is a positive regulator in chitin-induced stomatal closure and disease resistance.

Chitin, a fungal microbial-associated molecular pattern, triggers various defence responses in several plant systems. Although it induces stomatal closure, the molecular mechanisms of its interactions with guard cell signalling pathways are unclear. Based on screening of public microarray data obtained from the ATH1 Affymetrix and Arabidopsis eFP browser, we isolated a cDNA encoding a Ras-related nuclear protein 1 AtRAN1. AtRAN1 expression was enriched in guard cells in a manner consistent with involvement in the control of the stomatal movement. AtRAN1 mutation impaired chitin-induced stomatal closure and accumulation of reactive oxygen species and nitric oxide in guard cells. In addition, Atran1 mutant plants exhibited compromised chitin-enhanced plant resistance to both bacterial and fungal pathogens due to changes in defence-related genes. Furthermore, Atran1 mutant plants were hypersensitive to drought stress compared to Col-0 plants, and had lower levels of stress-responsive genes. These data demonstrate a previously uncharacterized signalling role for AtRAN1, mediating chitin-induced signalling.

Phospholipase D- and phosphatidic acid-mediated phospholipid metabolism and signaling modulate symbiotic interaction and nodulation in soybean (Glycine max).

Symbiotic rhizobium-legume interactions, such as root hair curling, rhizobial invasion, infection thread expansion, cell division and proliferation of nitrogen-fixing bacteroids, and nodule formation, involve extensive membrane synthesis, lipid remodeling and cytoskeleton dynamics. However, little is known about these membrane-cytoskeleton interfaces and related genes. Here, we report the roles of a major root phospholipase D (PLD), PLDα1, and its enzymatic product, phosphatidic acid (PA), in rhizobium-root interaction and nodulation. PLDα1 was activated and the PA content transiently increased in roots after rhizobial infection. Levels of PLDα1 transcript and PA, as well as actin and tubulin cytoskeleton-related gene expression, changed markedly during root-rhizobium interactions and nodule development. Pre-treatment of the roots of soybean seedlings with n-butanol suppressed the generation of PLD-derived PA, the expression of early nodulation genes and nodule numbers. Overexpression or knockdown of GmPLDα1 resulted in changes in PA levels, glycerolipid profiles, nodule numbers, actin cytoskeleton dynamics, early nodulation gene expression and hormone levels upon rhizobial infection compared with GUS roots. The transcript levels of cytoskeleton-related genes, such as GmACTIN, GmTUBULIN, actin capping protein 1 (GmCP1) and microtubule-associating protein (GmMAP1), were modified in GmPLDα1-altered hairy roots compared with those of GUS roots. Phosphatidic acid physically bound to GmCP1 and GmMAP1, which could be related to cytoskeletal changes in rhizobium-infected GmPLDα1 mutant roots. These data suggest that PLDα1 and PA play important roles in soybean-rhizobium interaction and nodulation. The possible underlying mechanisms, including PLDα1- and PA-mediated lipid signaling, membrane remodeling, cytoskeleton dynamics and related hormone signaling, are discussed herein.

GPR37 promotes the malignancy of lung adenocarcinoma via TGF-ß/Smad pathway.

This paper aimed to research the function and in-depth mechanism of GPR37 in lung adenocarcinoma (LUAD). Herein, based on TCGA and Oncomine databases, we revealed that GPR37 was expressed at high levels in LUAD, and upregulation of GPR37 was related to the poor outcomes. Furthermore, biological function experiments in vitro were utilized to assess whether GPR37 impacts malignant phenotype of LUAD cells. Gain- or loss-of-function assays indicated that the upregulation of GPR37 contributed to improving the proliferation, migration, and invasion of LUAD cells in vitro, while knockdown of GPR37 can inhibit the malignant biological behaviors. Then, we found that depletion of GPR37 resulted in a decrease in the expression of TGF-ß1 as well as the extents of Smad2 and Smad3 phosphorylation, while overexpression of GPR37 presented opposite outcomes. Altogether, our findings indicated that GPR37 is a potential oncogene of LUAD, and its promoting effects on the malignant progression of LUAD may be realized via TGF-ß/Smad pathway.