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Carotid stiffening is found to be present in patients with type 2 diabetes mellitus (T2DM) together with endothelial dysfunction and it remains unclear about the role of carotid elasticity in the development of diabetic vascular damage. The aim of the study was to investigate changes and significance of carotid artery elasticity in diabetic patients with or without microvascular complications using velocity vector imaging (VVI) analysis.Fifty participants were enrolled and divided into health Control group, the uncomplicated DM (uDM) group and the complicated DM (cDM) group. All of them underwent carotid ultrasound examinations. VVI was used to evaluate the common carotid artery (CCA) elasticity and intima-media thickness (IMT) was also measured. Flow-mediated dilation (FMD) was performed to detect the vascular endothelial function. Then differences and correlations of variables between three groups were compared and analyzed.CCA elasticity measured by VVI decreased significantly between three groups (P0.05), while FMD decreased significantly only in cDM group (P0.01) and only IMT in cDM group was significantly thicker than that of Control group (P0.05). Representative VVI variables were independently, negatively related to the known duration and microalbuminuria (P0.05). All VVI variables were significantly correlated with FMD (0.5≤|r|0.8, P0.001), and just a small part of VVI variables were significantly correlated with IMT (0.3≤ |r|0.5, P0.05).Compared with FMD, CCA elasticity measured by VVI showed more obvious changes in diabetic patients with different levels of vascular damage and may be considered as an alternative indicator in evaluating arterial status of T2DM. This article is protected by copyright. All rights reserved.

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Background. Epoxyeicosatrienoic acids (EETs), the metabolite of arachidonic acid by cytochrome P450 (CYP), reportedly serve as a vital endogenous protective factor in several chronic diseases. EETs are metabolized by soluble epoxide hydrolase (sEH). We have observed that prophylactic blocking sEH alleviates bleomycin- (BLM-) induced pulmonary fibrosis (PF) in mice. However, the underlying mechanism and therapeutic effects of EETs on PF remain elusive. Objective. In this study, we investigated the effect of CYP2J2/EETs on the activation of murine fibroblasts and their mechanisms. Results. we found that administration of the sEH inhibitor (TPPU) 7 days after the BLM injection also reversed the morphology changes and collagen deposition in the lungs of BLM-treated mice, attenuating PF. Fibroblast activation is regarded as a critical role of PF. Therefore, we investigated the effects of EETs on the proliferation and differentiation of murine fibroblasts. Results showed that the overexpression of CYP2J2 reduced the cell proliferation and the expressions of α-SMA and PCNA induced by transforming growth factor- (TGF-) β1 in murine fibroblasts. Then, we found that EETs inhibited the proliferation and differentiation of TGF-β1-treated-NIH3T3 cells and primary murine fibroblasts. Mechanistically, we found that 14,15-EET disrupted the phosphorylation of Smad2/3 murine fibroblasts by activating PPARγ, which was completely abolished by a PPARγ inhibitor GW9662. Conclusion. our study shows that EETs inhibit the activation of murine fibroblasts by blocking the TGF-β1-Smad2/3 signaling in a PPARγ-dependent manner. Regulating CYP2J2-EET-sEH metabolic pathway may be a potential therapeutic option in PF.

Dynamic observation of the behaviors of nanomaterials in the cellular environment is of great significance in mechanistic investigations on nanomaterial-based diagnostics and therapeutics. Realizing label-free observations with nanometer resolution is necessary but still has major challenges. Herein, we propose a NanoSuit-assisted liquid-cell scanning electron microscopy (NanoSuit-LCSEM) method that enables imaging of the behaviors of nanoparticles in living cells. Taking A549 cells and gold nanoparticles (AuNPs) as a cell-nanoparticle interaction model, the NanoSuit-LCSEM method showed a significantly improved resolution to 10 nm, which is high enough to distinguish single and two adjacent 30 nm AuNPs in cells. The continuous observation time for living cells is extended to 30 min, and the trajectories and velocities for the transmembrane movement of AuNP aggregates are obtained. This study provides a new approach for dynamic observation of nanomaterials in intact living cells and will greatly benefit the interdisciplinary research of nanomaterials, nanomedicine, and nanotechnology.

Necroptosis, a recently described form of programmed cell death, is the main way of alveolar epithelial cells (AECs) death in acute lung injury (ALI). While the mechanism of how to trigger necroptosis in AECs during ALI has been rarely evaluated. Long optic atrophy protein 1 (L-OPA1) is a crucial mitochondrial inner membrane fusion protein, and its deficiency impairs mitochondrial function. This study aimed to investigate the role of L-OPA1 deficiency-mediated mitochondrial dysfunction in AECs necroptosis. We comprehensively investigated the detailed contribution and molecular mechanism of L-OPA1 deficiency in AECs necroptosis by inhibiting or activating L-OPA1. First, our data showed that L-OPA1 expression was downregulated in the lungs and AECs under the lipopolysaccharide (LPS) challenge. Furthermore, inhibition of L-OPA1 aggravated the pathological injury, inflammatory response, and necroptosis in the lungs of LPS-induced ALI mice. In vitro, inhibition of L-OPA1 induced necroptosis of AECs, while activation of L-OPA1 alleviated necroptosis of AECs under the LPS challenge. Mechanistically, inhibition of L-OPA1 aggravated necroptosis of AECs by inducing mitochondrial fragmentation and reducing mitochondrial membrane potential. While activation of L-OPA1 had the opposite effects. In summary, these findings indicate for the first time that L-OPA1 deficiency mediates mitochondrial fragmentation, induces necroptosis of AECs, and exacerbates ALI in mice.

Athetis lepigone Möschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1 μM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15 μM] and ten plant volatiles, including (-)-limonene, α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.

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This paper investigates the effects of different amounts of N heteroatoms on the structural and electronic properties of pristine graphene and the adsorption behavior of Li atoms on N-doped graphene via first-principles calculations. The obtained results suggest that new N hexagonal structures are formed around the C hexagonal structure. The third-nearest neighbor structures are always maintained between the new N atoms and one of the original ones. Among the different N-doped graphene samples, the di- and tetra-N-doped and superlattice C3N exhibit semiconductor properties, while the others exhibit non-magnetic metallic properties. Studies on superlattice C3N reveal that N-doped graphene does not exhibit the aggregation of Li adatoms typical of pristine graphene. Single Li and two Li adatoms show non-magnetic metallic properties and semiconductor properties, respectively. The formation of multiple N-doped graphene samples explains the physical formation process of superlattice C3N. Their corresponding electronic properties and Li adsorption behavior are expected to motivate graphene applications in gas storage and sensing, catalysts, and biological devices.

To explore the value of human data from the Zhuang population via predicting the diameter of the hamstring tendon autograft in anterior cruciate ligament (ACL) reconstruction and determining the feasibility of preoperative ultrasound for prediction.In total, 24 Zhuang patients who underwent ACL reconstruction with a 4-strand semitendinosus and gracilis tendon autograft (4 S-STG) were enrolled in this study. Before the operation, the affected semitendinosus tendon (ST) was examined by ultrasonography, and its length, diameter, cross-sectional area, and circumference were measured. The patients' basic information and body data, ie, height, weight, body mass index, lower limb length injured, and thigh circumference injured, were recorded. Their ST and gracilis tendon lengths and diameters and 4 S-STG diameter were measured during the operation. A correlation analysis was conducted between the ultrasound measurement results and human data and intraoperative tendon measurements.The ST diameter measured by ultrasound was correlated with the ST length and ST diameter measured during operation, and the ST circumference measured by ultrasound was correlated with the ST diameter measured during operation. The patients' body weight can be used to distinguish a 4 S-STG diameter of ≥8 mm (P .01, mean difference = 11.59). The area under the receiver operating characteristic curve of body weight was 0.829. The final graft diameter ≥8 mm could be predicted with a body weight of 61.5 kg as the cutoff point; the sensitivity and specificity were 72.2% and 83.3%, respectively.In Zhuang patients undergoing ACL reconstruction with 4 S-STG, body weight more accurately predicted graft diameter than preoperative semitendinosus diameter.

Spodoptera litura is an important pest that causes significant economic damage to numerous crops worldwide. Sex pheromones (SPs) mediate sexual communication in S. litura and show a characteristic degree of rhythmic activity, occurring mainly during the scotophase; however, the specific regulatory mechanisms remain unclear. Here, we employed a genome-wide analysis to identify eight candidate circadian clock genes in S. litura. Sequence characteristics and expression patterns were analyzed. Our results demonstrated that some circadian clock genes might regulate the biosynthesis and perception of SPs by regulating the rhythmic expression of SP biosynthesis-related genes and SP perception-related genes. Interestingly, all potential genes exhibited peak expression in the scotophase, consistent with the SP could mediate courtship and mating behavior in S. litura. Our findings are helpful in elucidating the molecular mechanism by which circadian clock genes regulate sexual communication in S. litura.

Our previous study showed that triggering receptors expressed on myeloid cell-1 (TREM-1) was upregulated in bleomycin (BLM)-induced pulmonary fibrosis (PF) mouse model. However, the role of TREM-1 in the development of PF and its underlying mechanism remain unclear. Herein, we report that the prophylactical blockade of TREM-1 using a decoy peptide dodecapeptide (LR12) exerted protective effects against BLM-induced PF in mice, with a higher survival rate, attenuated tissue injury, and less extracellular matrix deposition. Interestingly, therapeutic blockade of TREM-1 at the early stage of fibrosis also attenuated BLM-induced PF, suggesting a non-inflammatory effect. More importantly, we observed that TREM-1 blockade with LR12 significantly reduced the expression of the senescence-relative protein, including p16, p21, p53, and γ-H2AX in the lungs of PF mice. Notably, TREM-1 was upregulated in alveolar epithelial cells (AECs) and correlated with the levels of senescence markers in BLM-treated mice. In vitro, activating TREM-1 with an agonistic antibody exacerbated BLM-induced senescence in MLE12 cells, a murine AEC cell line. Furthermore, prophylactic or therapeutic blockade of TREM-1 protected MLE12 cells from senescence induced by BLM or H

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory immune receptor potentiating acute lung injury (ALI). However, the mechanism of TREM-1-triggered inflammation response remains poorly understood. Here, we showed that TREM-1 blocking attenuated NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome activation and glycolysis in LPS-induced ALI mice. Then, we observed that TREM-1 activation enhanced glucose consumption, induced glycolysis, and inhibited oxidative phosphorylation in macrophages. Specifically, inhibition of glycolysis with 2-deoxyglucose diminished NLRP3 inflammasome activation of macrophages triggered by TREM-1. Hypoxia-inducible factor-1α (HIF-1α) is a critical transcriptional regulator of glycolysis. We further found that TREM-1 activation facilitated HIF-1α accumulation and translocation to the nucleus

Fangcang hospitals, as tentative hospitals built to treat a huge turnover of patients with mild coronavirus disease 2019 (COVID-19) infections, have played a pivotal role to slow down the pandemic spread in China in 2020. However, anxiety and sleep disorders remain tough to address during the treatments. In this study, group psychological intervention in combination with pulmonary rehabilitation exercises were conducted in the trial group for the patients with mild COVID-19 infections in a Fangcang Hospital to mitigate the patients' anxiety and sleep disorders, while conventional nursing methods were done in the control group, with 70 randomly picked patients in each group. Effects were assessed through questionnaire method using state anxiety questionnaire (SAI) and Pittsburgh sleep quality index scale (PQSI) rating investigation. Results showed that both SAI and PSQI scores of the trial group were significantly lower than those of the control group (P

The tobacco cutworm Spodoptera litura (Lepidoptera: Noctuidae) is a polyphagous pest with a highly selective and sensitive chemosensory system involved in complex physiological behaviors such as searching for food sources, feeding, courtship, and oviposition. However, effective management strategies for controlling the insect pest populations under threshold levels are lacking. Therefore, there is an urgent need to formulate eco-friendly pest control strategies based on the disruption of the insect chemosensory system. In this study, we identified 158 putative chemosensory genes based on transcriptomic and genomic data for S. litura, including 45 odorant-binding proteins (OBPs, nine were new), 23 chemosensory proteins (CSPs), 60 odorant receptors (ORs, three were new), and 30 gustatory receptors (GRs, three were new), a number higher than those reported by previous transcriptome studies. Subsequently, we constructed phylogenetic trees based on these genes in moths and analyzed the dynamic expression of various genes in head capsules across larval instars using quantitative real-time polymerase chain reaction. Nine genes–SlitOBP8, SlitOBP9, SlitOBP25, SlitCSP1, SlitCSP7, SlitCSP18, SlitOR34, SlitGR240, and SlitGR242–were highly expressed in the heads of 3- to 5-day-old S. litura larvae. The genes differentially expressed in olfactory organs during larval development might play crucial roles in the chemosensory system of S. litura larvae. Our findings substantially expand the gene inventory for S. litura and present potential target genes for further studies on larval feeding in S. litura.

We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) in mice. However, the exact mechanism has not been elucidated. Accumulating evidence points to the essential role of cellular senescence in NAFLD. Herein, we investigated whether restoring the balance of sEH/COX-2-mediated ARA metabolism attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor of sEH and COX-2, PTUPB, was used in our study to restore the balance of sEH/COX-2-mediated ARA metabolism. In vivo, NAFLD was induced by a high-fat diet (HFD) using C57BL/6J mice. In vitro, mouse hepatocytes (AML12) and mouse hepatic astrocytes (JS1) were used to investigate the effects of PTUPB on palmitic acid (PA)-induced hepatocyte senescence and its mechanism. PTUPB alleviated liver injury, decreased collagen and lipid accumulation, restored glucose tolerance, and reduced hepatic triglyceride levels in HFD-induced NAFLD mice. Importantly, PTUPB significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice. In vitro, the protein levels of γH2AX, p53, p21, COX-2, and sEH were increased in AML12 hepatocytes treated with PA, while Ki67 and PCNA were significantly decreased. PTUPB decreased the lipid content, the number of β-gal positive cells, and the expression of p53, p21, and γH2AX proteins in AML12 cells. Meanwhile, PTUPB reduced the activation of hepatic astrocytes JS1 by slowing the senescence of AML12 cells in a co-culture system. It was further observed that PTUPB enhanced the ratio of autophagy-related protein LC3II/I in AML12 cells, up-regulated the expression of Fundc1 protein, reduced p62 protein, and suppressed hepatocyte senescence. In addition, PTUPB enhanced hepatocyte autophagy by inhibiting the PI3K/AKT/mTOR pathway through Sirt1, contributing to the suppression of senescence. PTUPB inhibits the PI3K/AKT/mTOR pathway through Sirt1, improves autophagy, slows down the senescence of hepatocytes, and alleviates NAFLD.

Resveratrol has been extensively studied as the anti-cancer agent. A variety of resveratrol analogues have been developed with structural modification to improve its bioactivity. In this work, resveratrol analogues, compound 1-4, were designed and synthesized with the Stille–Heck reaction. These results showed compound 1–4 had better anticancer effect than that of parent resveratrol. Especially compound 1 ((E)-4,4′-(ethene-1,2-diyl)bis(3-methylphenol)) displayed the excellent cytotoxicity and high selectivity. The mechanism research indicated compound 1 inhibited cell proliferation by binary paths of cell cycle arrest in S phase regulated by cyclin A1/A2 and apoptosis induction mediated by Bax/Bcl2 in a prooxidant manner.

Ultrasound (US) can be used to evaluate the brain structure and nervous system damage. Patients with neurologic symptoms need rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging is currently the most sensitive and specific imaging method for evaluating neuropathologic conditions. This approach does present some challenges, such as the need to transport patients who may be seriously ill to the magnetic resonance imaging suite and the need for patients to remain for a considerable time. Cranial US provides a very valuable imaging method for clinicians, which can make a rapid diagnosis and evaluation without ionizing radiation. The main disadvantage of cranial US is its low sensitivity and specificity for subtle/early lesions. In recent years, with the rapid development of anatomic and functional US technology, the practicability of US diagnosis and intervention has been greatly improved. Ultrasound elastography may have the potential to improve the sensitivity and specificity of various cranial nerve conditions. Ultrasound elastography has received considerable critical attention, and an increasing number of studies have recognized its critical role in evaluating brain diseases. At present, US elastography has been applied to the evaluation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and hypoxic ischemic encephalopathy. The latest animal experiments and human clinical trial developments in the applications of US elastography for brain diseases are summarized in this review.

Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.

Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). Galectin-1 (Gal-1) has important anti-inflammatory properties in renal ischemia-reperfusion injury, arthritis, uveitis, and hepatitis. However, whether Gal-1 could protect against ALI is still poorly elucidated. The current study aimed to investigate the protective effects of Gal-1 against lipopolysaccharide (LPS)-induced ALI and the underlying mechanisms. Accordingly, we found that pretreatment with Gal-1 attenuated the lung tissue injury induced by LPS, with the recovery of lung function, protecting against the production of pro-inflammatory cytokines and oxidative stress. We also confirmed the therapeutic potential of Gal-1 on the survival rate of LPS-challenged mice. In vitro studies demonstrated the protective effects of exogenous Gal-1 through downregulating pro-inflammatory cytokines release and oxidative stress in primary macrophages challenged by LPS. In addition, Gal-1 suppressed TXNIP-NLRP3 inflammasome activation in ALI mice and LPS-treated primary macrophages partly through directly binding to the NLRP3 protein. Gal-1 alleviated LPS-induced lung injury via activation of Nrf-2, which may be associated with AMPK phosphorylation. Collectively, our experimental results firstly provided the support that Gal-1 effectively protected against LPS-induced ALI via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via phosphorylation of AMPK. These results suggest that Gal-1 could be a valuable therapeutic candidate in the treatment of ALI.

Spodoptera litura is an important pest that causes significant economic damage to numerous crops worldwide. Sex pheromones (SPs) mediate sexual communication in S. litura and show a characteristic degree of rhythmic activity, occurring mainly during the scotophase; however, the specific regulatory mechanisms remain unclear. Here, we employed a genome-wide analysis to identify eight candidate circadian clock genes in S. litura. Sequence characteristics and expression patterns were analyzed. Our results demonstrated that some circadian clock genes might regulate the biosynthesis and perception of SPs by regulating the rhythmic expression of SP biosynthesis-related genes and SP perception-related genes. Interestingly, all potential genes exhibited peak expression in the scotophase, consistent with the SP could mediate courtship and mating behavior in S. litura. Our findings are helpful in elucidating the molecular mechanism by which circadian clock genes regulate sexual communication in S. litura.

Background Uncontrolled inflammation is an important factor in the occurrence and development of acute lung injury (ALI). Fibroblast growth factor-inducible 14 (Fn14), a plasma membrane-anchored receptor, takes part in the pathological process of a variety of acute and chronic inflammatory diseases. However, the role of Fn14 in ALI has not yet been elucidated. This study aimed to investigate whether the activation of Fn14 exacerbated lipopolysaccharide (LPS)-induced ALI in mice. Methods In vivo, ALI was induced by intratracheal LPS-challenge combined with/without Fn14 receptor blocker aurintricarboxylic acid (ATA) treatment in C57BL/6J mice. Following LPS administration, the survival rate, lung tissue injury, inflammatory cell infiltration, inflammatory factor secretion, oxidative stress, and NLRP3 inflammasome activation were assessed. In vitro, primary murine macrophages were used to evaluate the underlying mechanism by which Fn14 activated the NLRP3 inflammasome. Lentivirus was used to silence Fn14 to observe its effect on the activation of NLRP3 inflammasome in macrophages. Results In this study, we found that Fn14 expression was significantly increased in the lungs of LPS-induced ALI mice. The inhibition of Fn14 with ATA downregulated the protein expression of Fn14 in the lungs and improved the survival rate of mice receiving a lethal dose of LPS. ATA also attenuated lung tissue damage by decreasing the infiltration of macrophages and neutrophils, reducing inflammation, and suppressing oxidative stress. Importantly, we found that ATA strongly inhibited the activation of NLRP3 inflammasome in the lungs of ALI mice. Furthermore, in vitro, TWEAK, a natural ligand of Fn14, amplified the activation of NLRP3 inflammasome in the primary murine macrophage. By contrast, inhibition of Fn14 with shRNA decreased the expression of Fn14, NLRP3, Caspase-1 p10, and Caspase-1 p20, and the production of IL-1β and IL-18. Furthermore, the activation of Fn14 promoted the production of reactive oxygen species and inhibited the activation of Nrf2-HO-1 in activated macrophages. Conclusions Our study first reports that the activation of Fn14 aggravates ALI by amplifying the activation of NLRP3 inflammasome. Therefore, blocking Fn14 may be a potential way to treat ALI.

Surgery for patients with adolescent idiopathic scoliosis (AIS) may change spinal sagittal alignment, and postoperative adding-on may affect spinal sagittal balance after reconstruction. This study was to investigate the effect of surgery on spinal sagittal alignment and the relationship between postoperative adding-on and spinal sagittal balance in patients with AIS.The hypothesis of this study was that the effect of surgery on AIS was associated with recovery of the spinal sagittal plane and that presence of postoperative adding-on might affect the spinal sagittal balance. Materials and methods This retrospective study enrolled 22 patients who received surgical treatment. Clinical, imaging and follow-up data were analyzed.After surgery, T1 slope (T1S) and thoracic kyphosis (TK) were significantly (P0.05) lower in patients with postoperative adding-on (16.73°±6.12° for T1S and 28.95°±11.3° for TK) than those without adding-on (24.82°±8.59° for T1S and 40.29°±12.08° for TK). At the last follow-up, cervical lordosis (CL), T1S, and TK were significantly (P0.05) lower in patients with adding-on (3.05°±11.41° for CL, 22.12°±3.68° for T1S, and 37.89°±8.97° for TK) than those without adding-on (15.94°±°13.6 for CL, 28.86°±4.26° for T1S, and 47.64°±7.1° for TK). The Cobb angle was significantly (19.65°±8.69° vs. 50.66°±11.46°; P0.001) decreased after compared with that before surgery. At the final follow-up, the Cobb angle (26.48°±9.61° vs. 19.65°±8.69°, P0.001), T1S (24.87°±5.11° vs. 20.04°±8.13°), and TK (41.88°±9.45° vs 33.53°±12.71°) all significantly (P0.01) increased compared with those immediately after surgery. The Cobb angle significantly (26.48°±9.61° vs. 50.66°±11.46°, P0.001) decreased while CL, T1S, and TK all significantly (8.32°±13.67° vs 2.47°±14.42° for CL, T1S 24.87°±5.11° vs. 21.28°±5.88° for T1S, and 41.88°±9.45° vs. 33.13°±10.97° for TK, P0.05) increased at the final follow-up compared with those before surgery.Surgery affects spinal sagittal alignment, and postoperative adding-on may affect spinal sagittal balance after reconstruction. Surgery as the ultimate approach for AIS has good effects but may result in some side effects.III, retrospective cohort study.

OBJECTIVES To investigate the value of 45° reverse oblique view of the carpal palm in diagnosing scaphoid waist fracture and displacement. METHODS Eighty-four patients with wrist injury and plain radiography including posteroanterior, lateral, Stecher, and 45° reverse oblique view of the wrist were analyzed for the detection rate in diagnosing scaphoid fractures and displacement. The degree of difficulty in the four views for detecting the scaphoid waist fracture and displacement was rated on a five-grade Likert scale. RESULTS Among 84 patients, scaphoid waist fractures occurred in 43, and fracture displacement in 32. A significantly (P

BACKGROUND: To investigate the relationship between sagittal alignment and coronal deformity in patients with adolescent idiopathic scoliosis (AIS) through analysis of the spinal imaging data. METHODS: Four hundred and fifty-four AIS patients who underwent anteroposterior and lateral radiography of the while spine were enrolled, and the spinal parameters of Cobb angle, cervical lordosis, C1-C2 angle, T1 slope, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt (PT), pelvic incidence (PI), cervical sagittal vertical axis (SVA), and spinal SVA were analyzed. RESULTS: The patients were divided into two groups according to the size of the Cobb angle: group A (Cobb angle ≤45°, n=414) and group B (Cobb angle >45°, n=40). In group A, the Cobb angle was in a medium negative correlation with the cervical lordosis angle (r=−0.637, P

Organ fibrosis often ends in eventual organ failure and leads to high mortality. Although researchers have identified many effector cells and molecular pathways, there are few effective therapies for fibrosis to date and the underlying mechanism needs to be examined and defined further. Epoxyeicosatrienoic acids (EETs) are endogenous lipid metabolites of arachidonic acid (ARA) synthesized by cytochrome P450 (CYP) epoxygenases. EETs are rapidly metabolized primarily via the soluble epoxide hydrolase (sEH) pathway. The sEH pathway produces dihydroxyeicosatrienoic acids (DHETs), which have lower activity. Stabilized or increased EETs levels exert several protective effects, including pro-angiogenesis, anti-inflammation, anti-apoptosis, and anti-senescence. Currently, intensive investigations are being carried out on their anti-fibrotic effects in the kidney, heart, lung, and liver. The present review provides an update on how the stabilized or increased production of EETs is a reasonable theoretical basis for fibrosis treatment.

Citrate has a prominent role as a substrate in cellular energy metabolism. Recently, citrate has been shown to drive inflammation. However, the role of citrate in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Here, we aimed to clarify whether extracellular citrate aggravated the LPS-induced ALI and the potential mechanism. Our findings demonstrated that extracellular citrate aggravated the pathological lung injury induced by LPS in mice, characterized by up-regulation of pro-inflammatory factors and over-activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in the lungs. In vitro, we found that citrate treatment significantly augmented the expression of NLRP3 and pro-IL-1β and enhanced the translocation of NF-κB/p65 into the nucleus. Furthermore, extracellular citrate plus adenosine-triphosphate (ATP) significantly increased the production of reactive oxygen species (ROS) in primary murine macrophages. Inhibiting the production of ROS with a ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the activation of NLRP3 inflammasome. Altogether, we conclude that extracellular citrate may serve as a damage-associated molecular pattern (DAMP) and aggravates LPS-induced ALI by activating the NLRP3 inflammasome.

In this paper, the effects of the two edges, i.e., S and Mo terminals for zigzag MoS2 nanoribbons, on Li atom adsorption and migration were studied from first principles. The lattice constants of NRs are width-dependent. The adsorption energy of single or multi-lithium adatoms is stronger when they are bound to the top of Mo atoms and when a Li atom is closer to the edge of a nanoribbon, particularly the S terminal edge. The symmetric two-sided adsorption configuration is more to form for multi-lithium adatoms. In addition, Li atoms initially adsorbed at the S or Mo terminal edge always prefer to diffuse along their corresponding edges. For other ones, they prefer to diffuse towards their nearby S or Mo terminal edge. These results indicate that zigzag MoS2 nanoribbons can significantly increase the Li binding energy while providing a high mobility path for Li. We hope our theoretical studies will inspire experimental studies on zigzag MoS2 nanoribbons for use as cathode materials.

Background Athetis lepigone, a noctuid moth feeding on more than 30 different crops worldwide, has evolved a sophisticated, sensitive, and specific chemosensory system to detect and discriminate exogenous chemicals. Odorant-binding proteins (OBPs) are the most important agent in insect chemosensory systems to be explored as an alternative target for environmentally friendly approaches to pest management. Results To investigate the olfactory function of A. lepigone OBPs (AlepOBPs), AlepOBP6 was identified and expressed in Escherichia coli. The binding affinity of the recombinant OBP to 20 different ligands was then examined using a competitive binding approach. The results revealed that AlepOBP6 can bind to two sex pheromones and ten maize volatiles, and its conformation stability is pH dependent. We also carried out a structure-function study using different molecular approaches, including structure modeling, molecular docking, and a mutation functional assay to identify amino acid residues (M39, V68, W106, Q107, and Y114) involved in the binding of AlepOBP6 to both sex pheromones and maize volatiles in A. lepigone. Conclusion These results suggest that AlepOBP6 is likely involved in mediating the responses of A. lepigone to sex pheromones and maize volatiles, which may play a pivotal function in mating, feeding, and oviposition behaviors. This study not only provides new insight into the binding mechanism of OBPs to sex pheromones and host volatiles in moths, but also contributes to the discovery of novel target candidates for developing efficient behavior disruptors to control A. lepigone in the future.

Alveolar epithelial cell death, inflammation, and oxidative stress are typical features of acute lung injury (ALI). Aloperine (Alo), an alkaloid isolated from Sophora alopecuroides, has been reported to display various biological effects, such as anti-inflammatory, immunoregulatory, and anti-oxidant properties. In this study, we investigated the effects and mechanisms of Alo in treating a lipopolysaccharide (LPS)-induced ALI in a murine model.The effects of Alo in LPS-induced ALI were investigated in C57BL/6 mice. The RIPK1 inhibitor (Nec-1) and the RIPK3 inhibitor (GSK'872) were used to evaluate the relationship of necroptosis, NF-κB activation, and PDC subunits in LPS-treated mouse alveolar epithelial cells (MLE-12). Then the effects of Alo on necroptosis, inflammation, and oxidative stress of LPS-stimulated MLE-12 cells were evaluated.Alo significantly attenuated histopathological lung injuries and reduced lung wet/dry ratio in LPS-induced ALI mice. Alo also remarkedly reduced total protein and neutrophils recruitment in bronchoalveolar lavage fluid of ALI mice. Meanwhile, Alo ameliorated the LPS-induced necroptosis in the lungs of ALI mice. The RIPK3 inhibitor GSK'872, but not the RIPK1 inhibitor Nec-1, reversed LPS-induced p65 phosphorylation and translocation to the nucleus in MLE-12 cells. GSK'872 also reversed the LPS-induced increase in ROS and binding of RIPK3 and PDC subunits in MLE-12 cells. Moreover, Alo down-regulated the levels of p-RIPK1, p-RIPK3, p-MLKL, p-p65, the translocation of p65 to the nucleus, and reduced the expression of IL-6 and IL-8 in LPS-stimulated MLE-12 cells. Alo also inhibited the binding of RIPK3 and PDC-E1α, PDC-E1β, PDC-E2, and PDC-E3 and the ROS production in LPS-treated MLE-12 cells.The present study validated the beneficial effects of Alo on LPS-induced ALI , suggesting Alo may be a new drug candidate against ALI.

The tobacco cutworm Spodoptera litura (Lepidoptera: Noctuidae) is a polyphagous pest with a highly selective and sensitive chemosensory system involved in complex physiological behaviors such as searching for food sources, feeding, courtship, and oviposition. However, effective management strategies for controlling the insect pest populations under threshold levels are lacking. Therefore, there is an urgent need to formulate eco-friendly pest control strategies based on the disruption of the insect chemosensory system. In this study, we identified 158 putative chemosensory genes based on transcriptomic and genomic data for S. litura, including 45 odorant-binding proteins (OBPs, nine were new), 23 chemosensory proteins (CSPs), 60 odorant receptors (ORs, three were new), and 30 gustatory receptors (GRs, three were new), a number higher than those reported by previous transcriptome studies. Subsequently, we constructed phylogenetic trees based on these genes in moths and analyzed the dynamic expression of various genes in head capsules across larval instars using quantitative real-time polymerase chain reaction. Nine genes-SlitOBP8, SlitOBP9, SlitOBP25, SlitCSP1, SlitCSP7, SlitCSP18, SlitOR34, SlitGR240, and SlitGR242-were highly expressed in the heads of 3- to 5-day-old S. litura larvae. The genes differentially expressed in olfactory organs during larval development might play crucial roles in the chemosensory system of S. litura larvae. Our findings substantially expand the gene inventory for S. litura and present potential target genes for further studies on larval feeding in S. litura.

Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.