The involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway.

BACKGROUND: Interferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated. METHODS: Using lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an in vivo and in vitro model was established. In vivo, Sting agonists and inhibitors were administered, while in vitro, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1ß, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the in vivo mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both in vivo and in vitro. RESULTS: In vitro experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1ß), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, in vitro experiments using HUVEC cell lines validated these findings. CONCLUSIONS: Our study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.

Effect of Intermittent Thoracic Paravertebral Block on Postoperative Nausea and Vomiting Following Thoracoscopic Radical Resection of the Lung Cancer: A Prospective Randomized Trial.

Purpose: To explore the benefits of ultrasound-guided intermittent thoracic paravertebral block (TPVB) combined with intravenous analgesia (PCIA) in alleviating postoperative nausea and vomiting (PONV) during video-assisted thoracic surgery (VATS). Patients and Methods: 120 patients with lung carcinoma undergoing VATS were included and divided into three groups: group S (single TPVB+PCIA), group I (intermittent TPVB+PCIA), and group P (PCIA). The patients' NRS scores, postoperative hydromorphone hydrochloride consumption, and intramuscular injection of bucinnazine hydrochloride were recorded. The incidence of PONV and complications were documented. Results: Compared with the group P, both group I and group S had significantly lower static NRS scores from 1-48 hours after the operation (P <0.05), and the dynamic NRS score of group I at the 1-48 hours after the operation were significantly decreased (P <0.05). Compared with the group P, the proportion of patients with PONV in group I was significantly lower (P <0.05), while there was no significant difference in group S. Moreover, the hospitalization period of patients in group I was significantly reduced compared with the other two groups (P <0.01), and the patient satisfaction was significantly increased compared with the group P (P <0.05). Conclusion: Intermittent TPVB combined with PCIA can reduce the postoperative pain and the occurrence of PONV.

The safety of preoperative carbohydrate drinks in extremely elderly patients assessed by gastric ultrasonography: a randomized controlled trial.

BACKGROUND: Modern perioperative guidelines encourage drinking oral carbohydrates 2 h before management. Nevertheless, research on the safety of preoperative carbohydrate drinks, particularly in extremely elderly patients is lacking. We aimed to evaluate the safety of carbohydrate drinks 2 h before surgery in extremely elderly patients (≥ 80 years) using gastric ultrasonography. METHODS: We conducted a randomized prospective comparative study of 70 patients aged over 80 years who were scheduled for total knee arthroplasty, hip fracture or humerus fracture surgery. These patients were randomly assigned to the carbohydrate group (n = 35), which fasted from midnight, except for drinking 355 mL of a carbohydrate-containing fluid 2 h before surgery, or the fasting group (n = 35), which fasted from midnight and drank no fluid before surgery. The primary outcome of the study was the cross-sectional area (CSA) of the gastric antrum in the right lateral decubitus position (RLDP) before surgery. The secondary outcomes included CSA in the supine position, intraoperative blood glucose levels and their variability coefficients, Perlas grade, and the visual analog scale of subjective feelings. RESULTS: The CSA in the RLDP and supine positions revealed no differences between the carbohydrate and fasting groups at 0 h preoperatively (P > 0.05). In the qualitative assessment, preoperative 0-h Perlas grading did not differ significantly between the groups (P > 0.05). From 2 h before surgery to transfer out of the post-anesthesia care unit, the average blood glucose level of patients in the carbohydrate group was significantly higher than that in the fasting group (P < 0.001) but remained within the normal range. Moreover, the blood glucose variability coefficient was significantly lower in the carbohydrate group than in the fasting group (P = 0.009). Oral intake of 355 mL carbohydrates before surgery significantly relieved patients' feelings (P < 0.001). CONCLUSION: Preoperative consumption of carbohydrate drinks 2 h before surgery is safe in "healthy" extremely elderly patients. In addition, preoperative drinking has potential value in maintaining ideal blood glucose levels and stable blood glucose fluctuations perioperatively and improving subjective perceptions of preoperative preparation. This finding warrants further investigation in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number ChiCTR1900024812), first registered on 29/07/2019.

Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread.

Background: The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably ß-lactams, constitutes a formidable challenge for healthcare and global public health management. Methods: This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features. Results: The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments. Conclusion: In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

Aristolochia mimics stink bugs to repel vertebrate herbivores via TRPA1 activation.

Mimicry is the phenomenon in which one species (the mimic) closely resembles another (the model), enhancing its own fitness by deceiving a third party into interacting with it as if it were the model. In plants, mimicry is used primarily to gain fitness by withholding rewards from mutualists or deterring herbivores cost-effectively. While extensive work has been documented on putative defence mimicry, limited investigation has been conducted in the field of chemical mimicry. In this study, we used field experiments, chemical analyses, behavioural assays, and electrophysiology, to test the hypothesis that the birthwort Aristolochia delavayi employs chemical mimicry by releasing leaf scent that closely resembles stink bug defensive compounds and repels vertebrate herbivores. We show that A. delavayi leaf scent is chemically and functionally similar to the generalized defensive volatiles of stink bugs and that the scent effectively deters vertebrate herbivores, likely through the activation of TRPA1 channels via (E)-2-alkenal compounds. This study provides an unequivocal example of chemical mimicry in plants, revealing intricate dynamics between plants and vertebrate herbivores. Our study underscores the potency of chemical volatiles in countering vertebrate herbivory, urging further research to uncover their potentially underestimated importance.

Predator-prey encounters: deciphering the robbery relationship between highwayman flies and their ant victims.

Examples of predator-prey interactions in which flies rob ants are uncommon. To date, this behavior has only been recorded in the genus Bengalia Robineau-Desvoidy (Bengaliinae, Diptera, Calliphoridae). These predatory flies ambush ants, and rob them of the food or offspring that they are carrying. However, because of the rarity of this behavior, the reasons and consequences (evolutionary advantages) are unknown, and indeed, the behavior has been sometimes considered anecdotal. In this study, we employed field investigations and behavioral analyses to investigate whether the sex of the fly Bengalia varicolor, or the weight and quality of the food carried by Pheidole nodus ants influenced fly-ant interactions in their natural habitats. We show that food weight and quality influenced the behavior of B. varicolor independent of the fly's sex. Robbing behavior by the flies was more successful when the food robbed was of high-quality and light in weight. Furthermore, the weight of the food robbed modulated the escape distance the flies could carry it. This then may affect the food quality and weight transported by the ants. This is a novel example of deciphering the relationship between highwayman flies and their ant victims. Given the widespread distribution of Bengalia flies, we suggest that such interspecific predator-prey encounters may shape the robbery interactions and the carrying behavior of further ant species in nature.

Knockdown of protein interacting with C α kinase 1 aggravates sepsis-induced acute liver injury by regulating the TLR4/NF-κB pathway.

Acute liver injury (ALI) may manifest at any phase of sepsis, yet an explicit therapeutic approach remains elusive. In this study, LPS and cecum ligation and puncture (CLP) were utilized to establish an inflammatory cell model and a murine model of sepsis-induced liver injury, respectively, aiming to explore the potential protective effect of protein interacting with C α kinase 1 (PICK1) on sepsis-induced ALI and its underlying mechanisms. In both the cell supernatant and the murine whole blood, the concentrations of inflammatory factors were quantified by ELISA, while the protein and mRNA expressions of PICK1, cleaved-PARP-1, caspase1, TLR4, IκBα, and NF-κB were assessed via western blot and qRT-PCR. The outcomes revealed that the knockdown of PICK1 increased the levels of inflammatory factors and apoptosis, alongside activation of TLR4/NF-κB signaling pathway-related factors in both in vivo and in vitro models. Moreover, the murine liver samples were subjected to Hematoxylin-Eosin (HE) staining for assessment of histopathological morphology. The HE staining and liver injury scoring results manifested a markedly exacerbated hepatic damage in PICK1 knockout mice as compared to WT mice following CLP. Furthermore, the liver macrophages were isolated from murine livers, and the expression and activity of the factors associated with the TLR4/NF-κB signaling pathway were verified through RT-qPCR and western blot, and EMSA assay demonstrated an augmented NF-κB activity subsequent to PICK1 knockout. Finally, the expression and localization of PICK1 in macrophages were further scrutinized via immunofluorescence, and the interaction between PICK1 and TLR4 was identified through co-immunoprecipitation. In conclusion, the knockdown of PICK1 appeared to modulate inflammatory factors by activating the TLR4/NF-κB signaling pathway, thereby exacerbating hepatic damage induced by sepsis.

LncRNA HCG18 loaded by polymorphonuclear neutrophil-secreted exosomes aggravates sepsis acute lung injury by regulating macrophage polarization.

Polymorphonuclear neutrophils (PMNs) exert significant roles in septic acute lung injury (ALI). Accumulating evidence suggests that PMN-derived exosomes (PMN-exo) are a novel subcellular entity that is the fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-exo in septic ALI and the underlying mechanisms remain unclear. Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in septic ALI, was used to induce PMN activation in vitro. Using an in vitro co-culture system, the rat alveolar macrophage cell line NR8383 was co-cultured with TNF-α-stimulated PMN-released exosomes (TNF-α-exo) to further confirm the results of the in vitro studies and explore the underlying mechanisms involved. A septic lung injury model was established by cecal ligation and puncture surgery, and PMN-exo were injected into septic mice through the tail vein, and then lung injury, inflammatory release, macrophage polarization, and apoptosis were examined. The results reported that TNF-α-exo promoted the activation of M1 macrophages after i.p. injection in vivo or co-culture in vitro. Furthermore, TNF-α-exo affected alveolar macrophage polarization by delivering HCG18. Mechanistic studies indicated that HCG18 mediated the function of TNF-α-exo by targeting IL-32 in macrophages. In addition, tail vein injection of si-HCG18 in septic mice significantly reduced TNF-α-exo-induced M1 macrophage activation and lung macrophage death, as well as histological lesions. In conclusion, TNF-α-exo-loaded HCG18 contributes to septic ALI by regulating macrophage polarization. These findings may provide new insights into novel mechanisms of PMN-macrophage polarization interactions in septic ALI and may provide new therapeutic strategies for patients with sepsis.

Progress and prospects of nanozymes for enhanced antitumor therapy.

Nanozymes are nanomaterials with mimicked enzymatic activity, whose catalytic activity can be designed by changing their physical parameters and chemical composition. With the development of biomedical and material science, artificially created nanozymes have high biocompatibility and can catalyze specific biochemical reactions under biological conditions, thus playing a vital role in regulating physiological activities. Under pathological conditions, natural enzymes are limited in their catalytic capacity by the varying reaction conditions. In contrast, compared to natural enzymes, nanozymes have advantages such as high stability, simplicity of modification, targeting ability, and versatility. As a result, the novel role of nanozymes in medicine, especially in tumor therapy, is gaining increasing attention. In this review, function and application of various nanozymes in the treatment of cancer are summarized. Future exploration paths of nanozymes in cancer therapies based on new insights arising from recent research are outlined.

Comprehensive Pan-Cancer Analyses of Immunogenic Cell Death as a Biomarker in Predicting Prognosis and Therapeutic Response.

Immunogenic cell death (ICD), a form of regulated cell death, is related to anticancer therapy. Due to the absence of widely accepted markers, characterizing ICD-related phenotypes across cancer types remained unexplored. Here, we defined the ICD score to delineate the ICD landscape across 33 cancerous types and 31 normal tissue types based on transcriptomic, proteomic and epigenetics data from multiple databases. We found that ICD score showed cancer type-specific association with genomic and immune features. Importantly, the ICD score had the potential to predict therapy response and patient prognosis in multiple cancer types. We also developed an ICD-related prognostic model by machine learning and cox regression analysis. Single-cell level analysis revealed intra-tumor ICD state heterogeneity and communication between ICD-based clusters of T cells and other immune cells in the tumor microenvironment in colon cancer. For the first time, we identified IGF2BP3 as a potential ICD regulator in colon cancer. In conclusion, our study provides a comprehensive framework for evaluating the relation between ICD and clinical relevance, gaining insights into identification of ICD as a potential cancer-related biomarker and therapeutic target.

Sugammadex Versus Neostigmine for Neuromuscular Block Reversal and Postoperative Pulmonary Complications in Patients Undergoing Resection of Lung Cancer.

OBJECTIVES: This study aimed to compare the effect of sugammadex and neostigmine on neuromuscular block reversal and the incidence of postoperative pulmonary complications in patients undergoing lung cancer resection. DESIGN: A double-blind, randomized, prospective study. SETTING: A single major urban teaching and university hospital. PARTICIPANTS: One hundred adult patients underwent elective radical resection of lung cancer under general anesthesia. INTERVENTIONS: Patients were assigned into neostigmine (0.05 mg/kg) + atropine 0.02 mg/kg group and sugammadex (2 mg/kg) group. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of any postoperative pulmonary complications, and the time to achieve 90% of train-of-four (TOF) after the administration of sugammadex or neostigmine. The secondary endpoints were the number of patients with TOF ratio (TOFr) <0.9 at the time of tracheal extubation, the incidence of readmission 30 days after discharge, and specific postoperative pulmonary complications. Results showed that the average time of recovery to TOFr ≥0.9 with sugammadex was 164.5 ± 27.7 seconds versus 562.9 ± 59.7 seconds with neostigmine + atropine treatment. Fewer sugammadex-treated patients did not achieve TOFr of 0.9 at the time of tracheal extubation than did neostigmine-treated participants. Patients in the sugammadex group had lower incidence of postoperative lung complications, and shorter durations of postanesthesia care unit stay and postoperative hospital stay than those in the neostigmine group. There was no significant difference in the incidence of readmission between the 2 groups. CONCLUSIONS: Administration of sugammadex provided faster recovery of rocuronium-induced neuromuscular block when compared with neostigmine. Moreover, for patients undergoing lung cancer resection, administration of sugammadex could reduce the incidence of postoperative pulmonary complications and duration of postoperative hospital stay.

Genetic diversity and structure of the endemic and endangered species Aristolochia delavayi growing along the Jinsha River.

The traditional medicinal plant, and endangered species Aristolochia delavayi (Aristolochiaceae) is an endemic species in China and occurs in the warm and dry areas along the Jinsha river. It is also a specific host of the larvae of Byasa daemonius, a vulnerable butterfly. In this study, 15 pairs of polymorphic microsatellite primers of A. delavayi were designed and screened based on the Simple Sequence Repeats (SSR) loci found by using the results of genome skimming. Based on these 15 SSR markers, the genetic diversity and structure of 193 individuals from ten natural populations were analyzed in detail. In comparison to other endemic and endangered plants in the region, the population of A. delavayi possess a relatively high genetic diversity (He = 0.550, I = 1.112). AMOVA analysis showed that 68.4% of the total genetic diversity was within populations and 31.6% of the variation occurred among populations. There was a significant genetic differentiation among natural populations of A. delavayi detectable, with low gene flow (Nm = 0.591). This might be attributed to geographical barriers and limited seed dispersal. To test the isolation by distance (IBD), we performed Mantel test, which showed a significant correlation between the geographic and genetic distances. In order to cope with the possible biases caused by IBD, we additionally performed Bayesian genetic cluster analyses and principal coordinate analysis (PCoA). The final cluster analysis revealed three groups with distinct geographical distribution. Habitat fragmentation and limited gene flow between these populations may be the main reasons for the current genetic structure. For conservation of this species, we suggest to divide its populations into three protection management units, with subsequent focus on the Yongsheng and Luquan populations which experienced a genetic bottleneck event in the past.

The Analgesic Efficacy of Erector Spinae Plane Blocks in Patients Undergoing Posterior Lumbar Spinal Surgery for Lumbar Fracture.

OBJECTIVE: To investigate the postoperative analgesic efficacy of ultrasound-guided lumbar erector spinae plane (ESP) blocks in patients undergoing posterior lumbar spinal surgery for lumbar spinal fractures. METHODS: A total of 80 patients who were scheduled for posterior internal fixation for lumbar spinal fractures were divided into a patient-controlled analgesia (PCA) group or a combined ESP-PCA group. Numeric rating scale at rest and during movement, postoperative sufentanil consumption, and accumulative and effective bolus presses of PCA were recorded at 6, 12, 24, and 48 hours postoperatively. Numeric rating scale at rest and during movement was the primary outcome. Incidence of postoperative nausea and vomiting during the first 24-48 hours, pruritus and chronic postoperative pain, and dose of pethidine for rescue analgesia were also recorded. RESULTS: Numeric rating scale at rest and during movement at 6, 12, and 24 hours was lower in the ESP-PCA group (P < 0.001, P < 0.001, P = 0.0016 at rest; all P < 0.001 during movement). Lumbar ESP blocks diminished accumulative bolus presses and effective bolus presses of PCA at 6, 12, 24, and 48 hours postoperatively. Besides, patients in the ESP-PCA group had fewer demands for sufentanil and pethidine. The incidence of postoperative nausea and vomiting in the ESP-PCA group was lower than that in PCA group. CONCLUSIONS: PCA combined with lumbar ESP blocks provided superior postoperative analgesia for patients with lumbar spinal fractures treated with posterior internal fixation. Lumbar ESP blocks decreased postoperative opioid consumption and incidence of postoperative nausea and vomiting, thereby enhancing postoperative recovery.

Reinstatement of the Chinese endemic species Styrax zhejiangensis.

Styrax zhejiangensis has been treated as a synonym of S. macrocarpus. Examination of herbarium specimens and observation of wild living plants demonstrates that S. zhejiangensis is a distinct species and is clearly distinguishable from S. macrocarpus through its flowering phenology in which leaves and flowers open simultaneously, its smaller corolla lobes and filaments, and its white-stellate-pubescent seeds. On this basis, we reinstate S. zhejiangensis as an accepted species. Photographic images and a distribution map of the two species are provided. A lectotype of S. zhejiangensis is also designated.

Comparison of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia: a randomized controlled trial.

BACKGROUND: The epidural dexmedetomidine combined with ropivacaine has been successfully used for labor analgesia. We compared the effects of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia. METHODS: Eighty nulliparous women were enrolled in the double-blind study and randomly divided into two groups. Group D received 0.5 µg/mL dexmedetomidine with 0.1% ropivacaine for epidural labor analgesia, and group S (control group) received 0.5 µg/mL sufentanil with 0.1% ropivacaine for labor analgesia. Hemodynamic parameters were monitored. Pain was assessed using a visual analog scale. The onset of epidural analgesia, duration of stages of labor, Ramsay Sedation Scale, blood loss, neonatal Apgar scores, umbilical artery blood pH and adverse effects, such as respiratory depression, nausea, vomiting, pruritus, and bradycardia, were recorded. RESULTS: Compared with the control group, visual analog scale values after cervical dilation >3 cm were lower in group D (P<0.05) and first-stage labor duration was shorter in group D (378.5±52.6 vs 406.5±58.2, P<0.05). Ramsay Sedation Scale values were higher in group D compared to the control group (2.8±0.6 vs 2.4±0.5, P<0.05). No significant differences in side effects were observed between the groups. CONCLUSION: Dexmedetomidine is superior to sufentanil in analgesic effect and duration in first-stage labor during epidural analgesia when combined with 0.1% ropivacaine (www.chictr.org.cn, registration ChiCTR-OPC-16008548).

PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT.

The role of oxidative stress has been well documented in the development of sepsis-induced acute lung injury (ALI). Protein interaction with C-kinase 1 (PICK1) participates in oxidative stress-related neuronal diseases. However, its function in lung infections and inflammatory diseases is not known. We therefore sought to investigate whether PICK1 is involved in sepsis-induced ALI. Cecal ligation and puncture (CLP) was performed in anesthetized wild type (WT) and PICK1 knock out (KO, PICK1-/-) mice with C57BL/6 background. At the time of CLP, mice were given fluid resuscitation. Mouse lungs were harvested at 24 and 72 h for Western blot analysis, qRT-PCR, BALF analysis, Hematoxylin and Eosin staining, TUNEL staining, maleimide staining, flow cytometry analysis, GCL, GSH, GSSG and cysteine levels measurement. A marked elevation of PICK1 mRNA and protein level were demonstrated in lung tissue, which was accompanied by increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consumption of glutathione (GSH). N-acetylcysteine (NAC), buthionine sulfoximine (BSO) and GSH-monoethyl ester (GSH-MEE) were injected into mice via caudal vein to regulate glutathione (GSH) level in lung. Alterations of lung GSH content induced PICK1 level change after CLP challenge. In PICK1-/- underwent with CLP, lung injury and survival were significantly aggravated compared with wild-type mice underwent with CLP. Concomitantly, CLP-induced lung cell apoptosis was exacerbated in PICK1-/- mice. The level of xCT, other than PKCα, in lung tissue was significantly lowered in PICK1-/- but not in wild type that underwent CLP surgery. Meanwhile, Nrf2 activation, which dominating xCT expression, was inhibited in PICK1-/- but not in wild type mice that underwent CLP surgery, as well. Moreover, higher level of PICK1 was detected in PBMCs of septic patients than healthy controls. Taken together, PICK1 plays a pivotal role in sepsis-induced ALI by regulating GSH synthesis via affecting the substrate-specific subunit of lung cystine/glutamate transporter, xCT.