Receptor-like protein kinases:Key regulators controlling root hair development in Arabidopsis thaliana

Root hairs are tubular outgrowths specifically differentiated from epidermal cells in a differentiation zone. The formation of root hairs greatly increases the surface area of a root and maximizes its ability to absorb water and inorganic nutrients essential for plant growth and development. Root hair development is strictly regulated by intracellular and intercellular signal communications. Cell surface-localized receptor-like protein kinases （P, LKs） have been shown to be important components in these cellular processes, tn this review, the functions of a number of key P, LKs in regulating Arabidopsis root hair development are discussed, especially those involved in root epidermal cell fate determination and root hair tip growth.

Synergy in Rice Immunity:Exploring Strategies of Coordinated Disease Defense Through Receptor-Like Kinases and Receptor-Like Cytoplasmic Kinases

Receptor-like kinases(RLKs)and receptor-like cytoplasmic kinases(RLCKs)play an indispensable role in the perception and transmission of extracellular signals in plants.In rice,these kinases actively participate in immune responses against a variety of pathogens,including fungi,bacteria,and viruses.However,research on the specific response mechanisms and the spectrum of different kinase activities against various pathogens remains insufficient.This review provides an in-depth and comprehensive overview of the types and functions of RLKs and RLCKs involved in disease resistance,emphasizing the central role of certain RLKs and RLCKs in the plant immune system.These kinases can recognize specific molecular patterns of pathogens and rapidly initiate an immune response in rice.Furthermore,the activity and functional regulation of these key kinases are tightly controlled by various post-translational modifications,such as phosphorylation and ubiquitination.This meticulous regulation ensures that the rice immune system's response is both precise and timely,effectively balancing the intensity of the immune response and preventing potential issues caused by either hyperactivity or insufficiency.By synthesizing current research findings,this review not only broadens our understanding of the role of RLKs and RLCKs in plant immunity but also provides new perspectives and strategies for future research on disease resistance breeding in rice.Future studies are expected to delve deeper into the signaling networks and regulatory mechanisms of these kinases,exploring their potential in agricultural production to develop rice varieties with enhanced disease resistance.

Receptor-like protein kinases in plant reproduction: Current understanding and future perspectives

Reproduction is a crucial process in the life span of flowering plants,and directly affects human basic requirements in agriculture,such as grain yield and quality.Typical receptor-like protein kinases(RLKs)are a large family of membrane proteins sensing extracellular signals to regulate plant growth,development,and stress responses.In Arabidopsis thaliana and other plant species,RLK-mediated signaling pathways play essential roles in regulating the reproductive process by sensing different ligand signals.Molecular understanding of the reproductive process is vital from the perspective of controlling male and female fertility.Here,we summarize the roles of RLKs during plant reproduction at the genetic and molecular levels,including RLK-mediated floral organ development,ovule and anther development,and embryogenesis.In addition,the possible molecular regulatory patterns of those RLKs with unrevealed mechanisms during reproductive development are discussed.We also point out the thought-provoking questions raised by the research on these plant RLKs during reproduction for future investigation.

Arabidopsis U-box E3 ubiquitin ligase PUB11 negatively regulates drought tolerance by degrading the receptor-like protein kinases LRR1 and KIN7

Both plant receptor-like protein kinases(RLKs)and ubiquitin-mediated proteolysis play crucial roles in plant responses to drought stress.However,the mechanism by which E3 ubiquitin ligases modulate RLKs is poorly understood.In this study,we showed that Arabidopsis PLANT U-BOX PROTEIN 11(PUB11),an E3 ubiquitin ligase,negatively regulates abscisic acid(ABA)-mediated drought responses.PUB11 interacts with and ubiquitinates two receptor-like protein kinases,LEUCINE RICH REPEAT PROTEIN 1(LRR1)and KINASE 7(KIN7),and mediates their degradation during plant responses to drought stress in vitro and in vivo.pub11 mutants were more tolerant,whereas Irr1 and kin7 mutants were more sensitive,to drought stress than the wild type.Genetic analyses show that the pub11 Irr1 kin7 triple mutant exhibited similar drought sensitivity as the Irr1 kin7 double mutant,placing PUB11 upstream of the two RLKs.Abscisic acid and drought treatment promoted the accumulation of PUB11,which likely accelerates LRR1 and KIN7 degradation.Together,our results reveal that PUB11 negatively regulates plant responses to drought stress by destabilizing the LRR1 and KIN7 RLKs.

Screening of Extracellular Binding Proteins of Rice Receptor-like Kinase CR4 by the Yeast Two-hybrid

[Objective] The research aimed to find the extracellular binding proteins of CR4.[Method] The extracellular domain of OsCR4 was as the bait protein,and the yeast two-hybrid was used to screen cDNA library of seedling which was cultivated 14 d.[Result] A lot of proteins which included a peroxide B（D26484）,a methionine thioredoxin reductase（ABF96078）and an unknown function protein were gained.[Conclusion] It provided the theory basis for studying the signal transduction mechanism of CR4.

Cloning and Hybrid Identification of Banana Receptor-like Protein Kinase Gene

[Objective] This study aimed to clone and identify the banana fruit receptor-like protein kinase gene.[Method] The cDNA phage libraries of banana fruit were adopted as the experimental materials to screen positive phage libraries of banana receptor-like protein kinase gene;cloning and sequence analysis of the gene were conducted,and the banana receptor-like protein kinase gene was identified by using in situ hybridization method.[Result] In this study,a 1 698 bp long banana receptor-like protein kinase gene was cloned from banana fruit,encoding 563 amino acids.Southern hybridization result confirmed that the banana receptor-like protein kinase gene was a multiple-copy gene from banana genome.[Conclusion] The study laid the foundation for further investigating the functions of banana receptor-like protein kinase gene in fruit.

RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition

BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

How many proteins interacting with symbiosis receptor-like kinase （SymRK） involved in nodulation？

Nodule formation is a tightly regulated process that integrates specific signal exchange and coordinated activation of developmental mechanisms to synchronize bacte-rial infection and organ development. Symbiosis receptor kinase （SymRK） is indispensable for symbiotic signal transduction of root nodule symbiosis （RNS） upon stimulation of root cells by microbial signaling molecules. But the protein turnover model of SymRK and the way for nodulation factor signals downstream transduction from SymRK are not clear. Over the past years, a number of proteins interacting with SymRK which required for root nodule symbiosis have been identified. Here we summarized structures and functions of these pro-teins, and concluded that major challenge would be revealing relations between them and the regulation mechanisms of SymRK in nodulation.

Involvement of Calcium dependent Protein Kinases in ABA regulation of Stomatal Movement

Patch clamp techniques were employed to investigate if calcium dependent protein kinases (CDPKs) be involved in the signal transduction pathways of stomatal movement regulation by the phytohormone abscisic acid (ABA) in Vicia faba. Stomatal opening was completely inhibited by external application of 1 μmol/L ABA, and such ABA inhibition was significantly reversed by the addition of CDPK inhibitor trifluoperazine (TFP). The inward whole cell K + currents were inhibited by 60% in the presence of 1 μmol/L intracellular ABA, and this inhibition was completely abolished by the addition of CDPK competitive substrate histone Ⅲ S. The results suggest that CDPKs may be involved in the signal transduction cascades of ABA regulated stomatal movements.

Characterization of a S-locus-related Receptor-like Kinase Cluster in Rice Chromosome 4

We have identified 14 S _locus glycoprotein (SLG)_related protein kinase genes in a 323 kb contig of rice (Oryza sativa L.) chromosome 4 and we detected the transcription pattern of this gene cluster by reverse transcription_polymerase reaction (RT_PCR). RT_PCR results revealed that nine putative genes were transcribed in rice and these genes had the different expression patterns: two genes are expressed predominantly in reproductive tissues while the other seven genes are expressed in both reproductive and vegetative tissues. Analysis of the predicted amino acid sequences demonstrated that the extracellular receptor domains are highly homologous to SLG of Brassica, whereas the cytoplasmic kinase domains contain conserved amino acids present in serine/threonine kinases.

Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatoRenic function in mouse testes

Cold-inducible RNA-binding protein （CIRP） is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purpose of this study was to investigate the functions of CIRP in the testes. We employed RNAi technique to knock down the expression of CIRP in the testes, and performed haematoxylin and eosin staining to evaluate morphological changes following knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal transferase-mediated dUTP nick end labelling （TUNEL） assay, and mitogen-activated protein kinase （MAPK） signalling pathways were investigated by Western blotting to determine the possible mechanism of apoptosis. We found that using siRNA is a feasible and reliable method for knocking down gene expression in the testes. Compared to controls, the mean seminiferous tubule diameter （MSTD） and the thickness of the germ cell layers decreased following siRNA treatment, whereas the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In conclusion, we discovered that downregulation of CIRP resulted in increased germ cell apoptosis, possibly viathe activation of the p44/p42, p38 and SAPK/JNK MAPK pathways.

Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway

AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.

Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal CA1 subregion

Objective： To explore the role that ceramide plays in the activation of mitogen-activated protein kinases （MAPKs） during cerebral ischemia and reperfusion. Methods： Rats were subjected to ischemia by the fourvessel occlusion （4-VO） method. The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia. Western blot was used to examine the activity of extracellular- signal regulated kinase （ERK） and c-Jun N-terminal protein kinase （JNK） using antibodies against ERK, JNK and diphosphorylated ERK and JNK. Results： At lh reperfusion post-ischemia, JNK reached its peak activity while ERK was undergoing a sharp inactivation （P 〈 0.05）. The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed （P 〈 0.05） by the sphingomyelinase inhibitor. Conclusion： The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia, promoting JNK activation and suppressing ERK activation, culminating in the ischemic lesion.

Mechanism of Retinoic Acid and Mitogen-activated Protein Kinases Regulating Hyperoxia Lung Injury

To investigate the protective effect of retinoic acid （RA） on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases （MAPKs）, gastation 21 d Sprague- Dawley （SD） fetuses （term = 22 d） were delivered by hysterotomy. Within 12-24 h of birth, premature rat pups were randomly divided into 4 groups （n= 12 each） ： air-exposed control group （group Ⅰ ） ; hyperoxia-exposed group （ group Ⅱ ）, air-exposed plus RA group （group Ⅲ ）, hyperoxia-exposed plus RA group （group Ⅳ）. Group Ⅰ , Ⅲ were kept in room air, and group Ⅱ , Ⅳ were placed in 85 % oxygen. The pups in groups Ⅲ and Ⅳ were intraperitoneally injected with RA （500 μg/kg every day）. All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling （TUNEL） staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs, JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma （P〈0.01）, and decreased significantly after RA treatment （P〈0.01）. The index of PCNA-positive cells was significantly decreased （P〈0.01）, and was significantly increased by RA treatment （P〈0.01）. The air-space size was significantly enlarged, secondary crests were markedly decreased in hyperoxia-exposed animals. RA treatment improved lung air spaces and secondary crests in air-exposed pups, hut had no effect on hyperoxia-exposure pups. Western blotting showed that the amounts of JNK, p38 and ERK proteins in hyperoxia-exposure or RA-treated lung tissues were same as those in untreated lung tissues （P〈0.05）, whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased （P〈0.01）, whereas p-JNK1/2 and p-p38 were markedly declined and p-ERK1/2 was further elevated by RA treatment （P〈0.01）. It is concluded that RA could decrease cell apoptosis and stimulate cell proliferation under hyperoxic condition. The protection Of RA on hyperoxia-induced lung injury was related＇to the regulation of MAP kinase activation.

Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis

Acute pancreatitis(AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis.

Signaling mechanisms in alcoholic liver injury: Role of transcription factors, kinases and heat shock proteins

Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes, fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NFKB, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury.

The wheat receptor-like cytoplasmic kinase TaRLCK1B is required for host immune response to the necrotrophic pathogen Rhizoctonia cerealis

Receptor-like cytoplasmic kinases(RLCKs)represent a large family of proteins in plants.In Arabidopsis and rice,several RLCKs in subfamily VII(RLCKs-VII)have been implicated in pathogen-associated molecular pattern-triggered immunity and basal resistance against bacterial and fungal pathogens.However,little is known about roles of RLCKs-VII of the important crop common wheat(Triticum aestivum)in immune responses.Here,we isolated a RLCK-VII-encoding gene from wheat,designated as TaRLCK1B,and investigated its role in host immune response to infection of a necrotrophic fungus Rhizoctonia cerealis that is a major pathogen of sharp eyespot,a destructive disease of wheat.RNA-sequencing and RT-qPCR analyses showed that transcriptional level of TaRLCK1B was significantly higher in sharp eyespot-resistant wheat cultivars than in susceptible wheat cultivars.The gene transcription was rapidly and markedly elevated in the resistant wheat cultivars by R.cerealis infection.The TaRLCK1B protein was closely related to OsRLCK176,a rice resistance-related RLCKs-VII,with 84.03%identity.Virus-induced gene silencing plus wheat response to R.cerealis assay results indicated that silencing of TaRLCK1 impaired resistance to R.cerealis.Meantime,silencing of TaRLCK1 significantly elevated both the content of H2 O2(a major kind of reactive oxygen species,ROS)and the transcriptional level of the ROS-generating enzyme-encoding gene RBOH,but repressed the expression of the ROS-scavenging enzyme-encoding gene CAT1 at 18 hours after inoculation(hai)with R.cerealis.Taken together,these data suggested that TaRLCK1B was required for the early immune response of wheat to R.cerealis through modulating ROS signaling in wheat.

OsSRK1,an Atypical S-Receptor-Like Kinase Positively Regulates Leaf Width and Salt Tolerance in Rice

Receptor-like kinases(RLKs)are important for plant growth,development and defense responses.The S-receptor protein kinases(SRKs),which represent an RLK subfamily,control the selfincompatibility among Brassica species.However,little information is available regarding SRK functions in rice.We identified a gene OsSRK1 encoding an atypical SRK.The transcript of OsSRK1 was induced by abscisic acid(ABA),salt and polyethylene glycol.OsSRK1 localized to the plasma membrane and cytoplasm.Leaf width was increased in OsSRK1-overexpression(OsSRK1-OX)transgenic rice plants,likely because of an increase in cell number per leaf.Furthermore,the expression levels of OsCYCA3-1 and OsCYCD2-1,which encode positive regulators of cell division,were up-regulated in leaf primordium of OsSRK1-OX rice plants relative to those in wild type.Meanwhile,the expression level of OsKRP1,which encodes cell cycle inhibitor,was down-regulated in the OsSRK1-OX plants.Therefore,it is deduced that OsSRK1 regulates leaf width by promoting cell division in the leaf primordium.Additionally,OsSRK1-OX plants exhibited enhanced ABA sensitivity and salt tolerance compared with wild type.These results suggest that OsSRK1 plays important roles in leaf development and salt responses in rice.

Arctigenin attenuates paraquat-induced human lung epithelial A549 cell injury by suppressing ROS/p38 mitogen-activated protein kinases-mediated apoptosis

BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ.We wondered whether arctigenin could also have a protective eff ect on PQ-induced ALI.METHODS:A PQ-induced A549 cell injury model was used,and the effect of arctigenin was determined by a cell counting kit-8(CCK-8)cell viability assay.In addition,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL)staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis.The generation of reactive oxygen species(ROS)was refl ected by dihydroethidium(DHE)staining and a 2’,7’-dichlorodihy drofluorescein diacetate(DCFH-DA)assay.Moreover,immunoblotting studies were used to assess the expression of mitogen-activated protein kinases(MAPKs)and p38 MAPK.RESULTS:Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner.Arctigenin also significantly reduced PQ-induced A549 cell apoptosis,as refl ected by the TUNEL assay and mitochondrial membrane potential assay,which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation.CONCLUSION:Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis,and arctigenin might be considered a potential candidate drug for PQ-induced ALI.