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Selenoprotein thioredoxin reductase 1 (TXNRD1) is a promising therapeutic target, with several inhibitors reported to inhibit TXNRD1 activity. These inhibitors have the potential for applications such as anti-tumor medications. Here, we present a protocol for assessing irreversible inhibitors of TXNRD1. We describe four assays covering cellular TXNRD activity measurement, recombinant enzyme-based activity determination, differential scanning fluorimetry (DSF), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This protocol will facilitate the screening and development of potential small-molecule inhibitors of TXNRD1., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Tree peony black spot (TPBS), mainly caused by Alternaria suffruticosae , is a common leaf disease on the ornamental peony, which poses a great threat to the flower buds in the current year and the flowering quality in the next year. However, there is only one fungicide registered for the control of this disease, difenoconazole. In order to avoid the severe problem of pathogen resistance caused by long-term use of difenoconazole, it is necessary to screen more chemical fungicides for the prevention and control of TPBS. In this study, the biological activities of flutolanil, phenamacril, pyraclostrobin, and boscalid on mycelial growth, conidial germination, germ tube elongation, and sporulation quantity of A . suffruticosae were determined, and the field control efficacy was tested to evaluate the preventive and therapeutic activities. Difenoconazole was used as a control simultaneously. The results showed that pyraclostrobin had the strongest inhibitory effects on the conidial germination, mycelium growth, germ tube elongation, and sporulation quantity, with the average EC 50 values of 0.0517, 0.5343, 0.0008, and 0.8068 μg/ml, respectively. The inhibitory activity of flutolanil on the four developmental stages of A . suffruticosae was weaker than that of the other three fungicides. Compared with flutolanil, boscalid, the other succinate dehydrogenase inhibitor, had more strong inhibitory effects on the mycelial growth and sporulation quantity, with the average EC 50 values of 3.8603 and 1.4760 μg/ml, respectively. Phenamacril had a moderate inhibitory level and had more inhibitory activity on conidial germination and germ tube elongation, with the average EC 50 values of 31.5349 and 5.2597 μg/ml, respectively. All of the four fungicides had no significant effects on the shape of spores and germ tubes. The control fungicide difenoconazole had the strongest inhibitory activity on mycelial growth, and the average EC 50 value was only 0.3297 μg/ml. However, its inhibitory activity on the other three growth stages was not high. In the field trials, pyraclostrobin had high control efficacy on TPBS even at low concentrations, reaching a minimum of 62.6293%, which was higher than that of difenoconazole. The other three fungicides had higher control efficacy at high concentrations but decreased significantly at low concentrations. Considering the dosage and control efficacy, pyraclostrobin was the first choice for the control of TPBS. Pyraclostrobin is the preferred alternative fungicide to difenoconazole for the prevention and control of TPBS in production., Competing Interests: The author(s) declare no conflict of interest.

To enable the timely adjustment of the control strategy of automobile active safety systems, enhance their capacity to adapt to complex working conditions, and improve driving safety, this paper introduces a new method for predicting road surface state information and recognizing road adhesion coefficients using an enhanced version of the MobileNet V3 model. On one hand, the Squeeze-and-Excitation (SE) is replaced by the Convolutional Block Attention Module (CBAM). It can enhance the extraction of features effectively by considering both spatial and channel dimensions. On the other hand, the cross-entropy loss function is replaced by the Bias Loss function. It can reduce the random prediction problem occurring in the optimization process to improve identification accuracy. Finally, the proposed method is evaluated in an experiment with a four-wheel-drive ROS robot platform. Results indicate that a classification precision of 95.53% is achieved, which is higher than existing road adhesion coefficient identification methods.

Mammalian cytosolic selenoprotein thioredoxin reductase (TXNRD1) is crucial for maintaining the reduced state of cellular thioredoxin 1 (TXN1) and is commonly up-regulated in cancer cells. TXNRD1 has been identified as an effective target in cancer chemotherapy. Discovering novel TXNRD1 inhibitors and elucidating the cellular effects of TXNRD1 inhibition are valuable for developing targeted therapies based on redox regulation strategies. In this study, we demonstrated that butein, a plant-derived small molecule flavonoid, is a novel TXNRD1 inhibitor. We found that butein irreversibly inhibited recombinant TXNRD1 activity in a time-dependent manner. Using TXNRD1 mutant variants and LC-MS, we identified that butein modifies the catalytic cysteine (Cys) residues of TXNRD1. In cellular contexts, butein promoted the accumulation of reactive oxygen species (ROS) and exhibited cytotoxic effects in HeLa cells. Notably, we found that pharmacological inhibition of TXNRD1 by butein overcame the cisplatin resistance of A549 cisplatin-resistant cells, accompanied by increased cellular ROS levels and enhanced expression of p53. Taken together, the results of this study demonstrate that butein is an effective small molecule inhibitor of TXNRD1, highlighting the therapeutic potential of inhibiting TXNRD1 in platinum-resistant cancer cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p -toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.

The study of solid/liquid interface is of great significance for understanding various phenomena such as the nanostructure of the interface, liquid wetting, crystal growth and nucleation. In this work, the nanostructure of the pyridinium ionic liquid [BPy]BF 4 on different gold surfaces was studied by molecular dynamics simulation. The results indicate that the density of the ionic liquids near the gold surface is significantly higher than that in the bulk phase. Cation's tail (the alkyl chain) orients parallel to the surface under all studied conditions. Cation's head (the pyridine ring) orientation varies from parallel to perpendicular, which depends on the temperature and corrugation of the Au(hkl) surface. Interestingly, analysis of simulated mass and number densities revealed that surface corrugation randomizes the cations packing. On smooth Au(111) and Au(100) surfaces, parallel and perpendicular orientations are well distinguished for densely packed cations. While on corrugated Au(110), cations' packing density and order are decreased. Overall, this study explores the adsorption effect of the gold surface on ionic liquids, providing some valuable insights into their behavior on the solid/liquid interface., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: The aim of this study is to examine the role of activities of daily living performance (ADLs) and psychological distress in mediating the process by which health behaviors affect QOL., Methods: A non-probabilistic study was conducted among 1,065 older adult people older than 60 years. Participants were assessed using the Barthel Index, Functional Activities Questionnaire (FAQ), Kessler Psychological Distress Scale (K10), Australian Active Survey, and EQ-VAS score. The SPSS22.0 software was used to analyze the differences in QOL scores among older adults with different demographic characteristics. Pearson correlation analysis was used to analyze the correlation between health behaviors, psychological distress, ADLs, and QOL. Amos23.0 software was used to construct structural equation model (SEM) to analyze the path of health behavior affecting QOL and the mediating role of BADLs, IADLs and psychological distress., Results: (1) The direct effect of health behaviors on QOL was not significant in the model; (2) ADLs had multiple mediating effects on the relationship between health behaviors and QOL, and the incidence of ADL limitation was negatively correlated with the reported QOL in the older adult; (3) Psychological distress had a significant mediating effect on the relationship between health behaviors and QOL., Conclusion: The results of this study elucidated the mechanisms of the correlation between health behaviors and QOL, and added to the existing literature. In addition, these mediating factors and indirect pathways have been identified as targets for intervention to improve the QOL of older adult individuals, which is important for achieving healthy aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Xu, Gao and Zheng.)

Thioredoxin reductase (TXNRD) is a selenoprotein that plays a crucial role in cellular antioxidant defense. Previously, a distinctive guiding bar motif was identified in TXNRD1, which influences the transfer of electrons. In this study, utilizing single amino acid substitution and Excitation-Emission Matrix (EEM) fluorescence spectrum analysis, we discovered that the guiding bar communicates with the FAD and modulates the electron flow of the enzyme. Differential Scanning Fluorimetry (DSF) analysis demonstrated that the aromatic amino acid in guiding bar is a stabilizer for TXNRD1. Kinetic analysis revealed that the guiding bar is vital for the disulfide reductase activity but hinders the selenocysteine-independent reduction activity of TXNRD1. Meanwhile, the guiding bar shields the selenocysteine residue of TXNRD1 from the attack of electrophilic reagents. We also found that the inhibition of TXNRD1 by caveolin-1 scaffolding domain (CSD) peptides and compound LCS3 did not bind to the guiding bar motif. In summary, the obtained results highlight new aspects of the guiding bar that restrict the flexibility of the C-terminal redox motif and govern the transition from antioxidant to pro-oxidant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Carbon nanotubes (CNTs) have potential prospects in disease treatment, so it is of great significance to study CNTs as the possible inhibitors of RNA-dependent RNA polymerase (RdRp). Through the way of using the RdRp of SARS-COV-2 as a model, five armchair single-walled carbon nanotubes (SWCNTs) (namely Dn, which stands for CNTs (n, m = n), n  = 3-7) and RdRp have been selected to study the interactions by means of molecular docking and molecular dynamics simulation. After five SWCNT-RdRp complex systems have been subjected to the molecular dynamics simulations of 100 ns, and Molecular Mechanics Poisson - Boltzmann Surface Area (MMPBSA) has been used to calculate the binding free energy, it is found that the binding free energy of the D6 system (-189.541 kJ/mol) is significantly higher than that of the other four systems, and most of the amino acids with strong positive effects on binding are usually basic amino acids. What's more, in the further investigation of the specific interaction mechanism between CNT (6,6) and RdRp, it is revealed that the three amino acid residues LYS545, ARG553 and ARG555 located in the nucleoside triphosphate (NTP) entry channel all have strong effects. In addition, it is also observed that when ARG555 has been inserted into SWCNT, a stable structure will be formed, which will break the original NTP entry channel structure and inhibit virus replication. Therefore, it can be concluded that certain specific types of SWCNT, such as CNT (6,6), could be potential small molecule inhibitors in the treatment of coronavirus.Communicated by Ramaswamy H. Sarma.

Direct analysis in real time (DART) enables direct desorption and ionization of analytes, bypassing the time-consuming chromatographic separation traditionally required for mass spectrometry (MS) analysis. However, DART-MS suffers from matrix interference of complex samples, resulting in compromised detection sensitivity and quantitation accuracy. In this study, DART-MS was combined with differential mobility spectrometry (DMS) to provide an additional dimension of post-ionization ion mobility separation within a millisecond time scale, compensating for the lack of separation in DART-MS analysis. As proof-of-concept, primary aromatic amines (PAAs), a class of potentially hazardous chemicals, were analyzed in various toy products, including bubble solutions, finger paints, and plush toys. In addition to commercial Dip-it glass rod and metal mesh sampling tools, a customized rapid extractive evaporation device was designed for the accelerated extraction and sensitive analysis of solid toy samples. The incorporation of DMS in DART-MS analysis enabled the rapid separation and differentiation of isomeric analytes, leading to improved accuracy and reliability. The developed protocols were optimized and validated, achieving good linearity with correlation coefficients greater than 0.99 and acceptable repeatability with relative standard deviations less than 10%. Moreover, satisfactory sensitivity was realized with limits of detection and quantitation ranges of 0.2-5 and 1-20 μg/kg (μg/L) for the 11 PAA analytes. The established methodology was applied for the analysis of real toy samples ( n = 18), which confirmed its appealing potential for toy safety screening and consumer health protection.

Fusarium pseudograminearum is the dominant pathogen causing Fusarium crown rot (FCR) of wheat. Phenamacril is a 2-cyanoacrylate fungicide, having a control effect on diseases caused by Fusarium spp. The objective of this study was to investigate the inhibitory effect of phenamacril on F. pseudograminearum and its control efficacy against FCR. The results showed that phenamacril had a strong inhibitory effect on the mycelial growth of F. pseudograminearum , EC 50 values of phenamacril to 63 tested strains were in the range of 0.0998 to 0.5672 μg/ml, and the average EC 50 value was 0.3403 ± 0.0872 μg/ml and could be used as the baseline sensitivity of F. pseudograminearum to phenamacril. Phenamacril reduced the germination rate of conidia of F. pseudograminearum , and the EC 50 value was 5.0273 to 26.4814 μg/ml. In addition, we found that phenamacril had a teratogenic effect on conidia and blastotubules, which increased the ratio of conidial germination from the middle cells and showed high efficacy on the sporulation quantity of F. pseudograminearum with an EC 50 value in the range of 0.0770 to 0.1064 μg/ml. There was no significant correlation between the sensitivity of F. pseudograminearum to phenamacril and its sensitivity to fludioxonil, carbendazim, tebuconazole, and kresoxim-methyl. In vitro and greenhouse assays showed that the treatment with 0.125 μl of active ingredient per gram recorded the best control effect on wheat crown rot, reaching 87.8 and 77.3%, respectively. In two experimental sites in Luoyang, phenamacril also had great control effect against FCR, reaching 83.9%. It was proven that phenamacril has a superior control effect against FCR. This study has laid a foundation for the study of the mechanism of action of phenamacril against F. pseudograminearum and provided a theoretical basis for the application of phenamacril to control FCR., Competing Interests: The author(s) declare no conflict of interest.

Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor). Melanin, especially eumelanin, has antioxidant properties, and MGST1 KD melanoma cells are under higher oxidative stress, with increased reactive oxygen species, decreased antioxidant capacities, reduced energy metabolism and ATP production, and lower proliferation rates in 3D culture. In mice, when compared to nontarget control, Mgst1 KD B16 cells had less melanin, more active CD8 + T cell infiltration, slower growing tumors, and enhanced animal survival. Thus, MGST1 is an integral enzyme in melanin synthesis and its inhibition adversely influences tumor growth., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023. Published by Elsevier Inc.)

Multidrug-resistant (MDR) Gram-negative bacteria have become a global threat to human life and health, and novel antibiotics are urgently needed. The thioredoxin (Trx) system can be used as an antibacterial target to combat MDR bacteria. Here, we found that two active gold(I) selenium N-heterocyclic carbene complexes H7 and H8 show more promising antibacterial effects against MDR bacteria than auranofin. Both H7 and H8 irreversibly inhibit the bacterial TrxR activity via targeting the redox-active motif, abolishing the capacity of TrxR to quench reactive oxygen species (ROS) and finally leading to oxidative stress. The increased cellular superoxide radical levels impact a variety of functions necessary for bacterial survival, such as cellular redox balance, cell membrane integrity, amino acid metabolism, and lipid peroxidation. In vivo data present much better antibacterial activity of H7 and H8 than auranofin, promoting the wound healing and prolonging the survival time of Carbapenem-resistant Acinetobacter baumannii (CRAB) induced peritonitis. Most notably in this study, we revealed the influence of gold(I) complexes on both the Trx system and the cellular metabolic states to better understand their killing mechanism and to support further antibacterial drug design., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Milk thistle is a traditional medicinal herb. Silybin is a medicinal component found in the seed coat of milk thistle, which has liver-protective and anti-cancer properties. Conventional studies have focused on the extraction of silybin with organic reagents, which was inapplicable to the food industry. This study aims to develop a fermented milk containing silybin and protein from the milk thistle seeds. A three step procedure was developed, comprising homogenization of milk thistle seeds, NaHCO 3 heat treatment, and microbial fermentation. The silybin was characterized by high performance liquid chromatography, and the protein was quantified and electrophorized. It was found that the homogenization step was essential for the preparation of protein, and the NaHCO 3 heat treatment was the crucial step in obtaining silybin. The optimal NaHCO 3 treatment settings were 1% NaHCO 3 , 60°C, and 3 h, and the optimal strains for microbial fermentation were L131 ( Rummeliibacillus stabekisii ) and RS72 ( Lactobacillus plantarum ). The silybin yield in the fermented milk reached 11.24-12.14 mg/g seeds, accounting for 72.6-78.4% of the total silybin in the milk thistle seeds, and the protein yield reached 121.8-129.6 mg/g seeds. The fermented milk had a slightly sweet yoghurt-like flavor and could be used as a dietary supplement for silybin and protein.

Fusarium pseudograminearum has been identified as a significant pathogen. It causes Fusarium crown rot (FCR), which occurs in several major wheat-producing areas in China. Chemical control is the primary measure with which to control this disease. In this study, transcriptome sequencing (RNA-Seq) was used to determine the different mechanisms of action of four frequently used fungicides including carbendazim, pyraclostrobin, tebuconazole, and phenamacril on F. pseudograminearum . In brief, 381, 1896, 842, and 814 differentially expressed genes (DEGs) were identified under the carbendazim, pyraclostrobin, tebuconazole, and phenamacril treatments, respectively. After the joint analysis, 67 common DEGs were obtained, and further functional analysis showed that the ABC transported pathway was significantly enriched. Moreover, FPSE_04130 ( FER6) and FPSE_11895 ( MDR1 ), two important ABC multidrug transporter genes whose expression levels simultaneously increased, were mined under the different treatments, which unambiguously demonstrated the common effects. In addition, Mfuzz clustering analysis and WGCNA analysis revealed that the core DEGs are involved in several critical pathways in each of the four treatment groups. Taken together, these genes may play a crucial function in the mechanisms of F. pseudograminearum 's response to the fungicides stress.

Background: Superior mesenteric artery embolism (SMAE) is a rare cause of acute abdomen, and the fatality rate is extremely high if it is not diagnosed and treated in time. Due to the lack of knowledge and experience of nonspecialist physicians, it is easy to misdiagnose. Radiofrequency ablation (RFA) has become the first-line treatment strategy for atrial fibrillation (AF). Thromboembolic events are some of the major complications after RFA, whereas SMAE is rarely reported., Case Presentation: A 70 year-old woman with paroxysmal AF who regularly took anticoagulant drugs for 3 months experienced abdominal pain after RFA. At the outset, she was misdiagnosed as mechanical intestinal obstruction. When the patient presented with blood in the stool, abdominal enhancement computed tomography was conducted and showed a small bowel perforation. Immediate laparotomy was performed, and the final diagnosis was SMAE., Conclusion: It is suggested that for unexplained abdominal pain after RFA of AF, the possibility of SMAE should be considered, and a targeted examination should be carried out in time to confirm the diagnosis and give appropriate treatment., (© 2023. The Author(s).)

Cadmium (Cd) as a ubiquitous toxic heavy metal in the environment, causes severe hazards to human health, such as cellular stress and organ injury. Selenium (Se) was reported to reduce Cd toxicity and the mechanisms have been intensively studied so far. However, it is not yet crystal clear whether the protective effect of Se against Cd-induced cytotoxicity is related to selenoproteins in nerve cells or not. In this study, we found that Cd inhibited selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1) and decreased the expression level of TrxR1, resulting in cellular oxidative stress, and Se supplements ameliorated Cd-induced cytotoxicity in SH-SY5Y cells. Mechanistically, the detoxification of Se against Cd is attributed to the increase of the cellular TrxR activity and upregulated TrxR1 protein level, culminating in strengthened antioxidant capacity. Results showed that Se supplements attenuated the ROS production and apoptosis in SH-SY5Y cells, and significantly mitigated Cd-induced SH-SY5Y cell death. This study may be a valuable reference for shedding light on the mechanism of Cd-induced cytotoxicity and the role of TrxR1 in Se-mitigated cytotoxicity of Cd in neuroblast cells, which may be helpful for understanding the therapeutic potential of Cd and Se in treating or preventing neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Macrophages secrete a variety of pro-inflammatory cytokines in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) but abnormal release of cytokines unfortunately promotes cytokine storms. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis (MS) treatment, has been found as an effective therapeutic agent for resolution. In this study, the anti-inflammatory effect of DMF was found to correlate to selenoprotein thioredoxin reductase 1 (TXNRD1). DMF irreversibly modified the Sec 498 residue and C-terminal catalytic cysteine residues of TXNRD1 in a time- and dose-dependent manner. In LPS-stimulated RAW 264.7 cells, cellular TXNRD activity was increased through up-regulation of the protein level and DMF inhibited TXNRD activity and the nitric oxide (NO) production of RAW 264.7 cells. Meanwhile, the inhibition of TXNRD1 by DMF would contribute to the redox regulation of inflammation and promote the nuclear factor erythroid 2-related factor 2 (NRF2) activation. Notably, inhibition of cellular TXNRD1 by auranofin or TRi-1 showed anti-inflammatory effect in RAW 264.7 cells. This finding demonstrated that targeting TXNRD1 is a potential mechanism of using immunometabolites for dousing inflammation in response to pathogens and highlights the potential of TXNRD1 inhibitors in immune regulation.

The nonnegligible reason for the poor prognosis of hepatocellular carcinoma (HCC) is resistance to conventional chemotherapy. Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can reengage the tumor-specific immune system. ICD can improve the clinical outcomes of chemotherapeutics by promoting a long-term cancer immunity. The discovery of potential ICD inducers is emerging as a promising direction. In the present study, micheliolide (MCL), a natural guaianolide sesquiterpene lactone, was screened out by the virtual screening strategies, identified as an inhibitor of thioredoxin reductase (TrxR) and was evaluated to have high potential to induce ICD. Here, we showed that MCL induced ICD-associated DAMPs (damage-associated molecular patterns, such as CRT exposure, ATP secretion and HMGB1 release). MCL significantly triggered the regression of established tumors in an immunocompetent mouse vaccine model, and induced ICD (DCs maturation, the stimulation of CD4 + , and CD8 + T-cells responses) in vivo. Mechanistically, we found that the magnitude of ICD-associated effects induced upon exposure of HCC cells to MCL was dependent on the generation of reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ERS). In addition, the suppression of ROS normalized MCL-induced ERS, in contrast, the downregulation of TrxR synergized with the ERS driven by MCL. We also systematically detected the H 2 O 2 generation using Hyper7 sensors in HCC cells exposed to MCL. Notably, MCL inhibited the development of HCC organoids. Collectively, our results reveal a potential association between the TrxR inhibitors and ICD, presenting valuable insights into the MCL-activated ICD in HCC cells., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Fusarium head blight (FHB), caused mainly by Fusarium graminearum , is one of the most devastating diseases of wheat. Prothioconazole is a broad-spectrum demethylation inhibitor fungicide with excellent efficacy against FHB. In this study, 235 strains of F. graminearum collected from different regions of Henan Province of China in 2016, 2017, and 2018 were randomly selected. The sensitivity of F. graminearum to prothioconazole was determined by the mycelial growth inhibition method. The results showed that the half maximal effective concentration (EC 50 ) values of F. graminearum to prothioconazole ranged from 0.4742 to 3.4403 μg/ml, and the average EC 50 value was 1.7758 ± 0.6667 μg/ml. The sensitivity frequency distribution presented a consequent unimodal curve, and thus the average EC 50 value can be established as the baseline sensitivity of F. graminearum to prothioconazole. Ten strains of prothioconazole-resistant mutants were obtained by fungicide taming, and the resistance factor of the mutants ranged from 5.71 to 12.32. The genetic stability assay showed that resistance can be inherited stably for 10 generations. All mutants displayed different degrees of defects in vegetative growth, conidia formation, and pathogenicity compared with the parental strain. These results indicated that F. graminearum has a low risk of resistance to prothioconazole. Cross-resistance assay showed that no cross-resistance was found between prothioconazole and carbendazim, tebuconazole, phenamacril, and pydiflumetofen. Among all mutants, sequence analysis showed that no mutation site was found in cyp51A and cyp51B . Real-time PCR assays showed that the expression levels of cyp51A and cyp51B of the mutants were significantly increased after prothioconazole treatment for 24 h. In summary, our study provided a theoretical basis for the resistance risk assessment of F. graminearum to prothioconazole and scientific application of prothioconazole in controlling FHB.

Fusarium pseudograminearum causes crown rot in wheat. This study aimed to assess the effects of the bacterial strain QTH8 isolated from Cotinus coggygria rhizosphere soil against F. pseudograminearum . Bacterial strain QTH8 was identified as Bacillus halotolerans in accordance with the phenotypic traits and the phylogenetic analysis of 16S rDNA and gyrB gene sequence. Culture filtrates of bacterial strain QTH8 inhibited the mycelial growth of F. pseudograminearum and resulted in mycelial malformation such as tumor formation, protoplast condensation, and mycelial fracture. In addition, bacterial strain QTH8 also inhibited the mycelial growth of Hainesia lythri , Pestalotiopsis sp., Botrytis cinerea , Curvularia lunata , Phyllosticta theaefolia , Fusarium graminearum , Phytophthora nicotianae , and Sclerotinia sclerotiorum . The active compounds produced by bacterial strain QTH8 were resistant to pH, ultraviolet irradiation, and low temperature, and were relatively sensitive to high temperature. After 4 h exposure, culture filtrates of bacterial strain QTH8-when applied at 5%, 10%, 15%, 20%, 25%, and 30%-significantly reduced conidial germination of F. pseudograminearum . The coleoptile infection assay proved that bacterial strain QTH8 reduced the disease index of wheat crown rot. In vivo application of QTH8 to wheat seedlings decreased the disease index of wheat crown rot and increased root length, plant height, and fresh weight. Iturin, surfactin, and fengycin were detected in the culture extract of bacterial strain QTH8 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Bacterial strain QTH8 was identified for the presence of the ituC , bacA , bmyB , spaS , srfAB , fend , and srfAA genes using the specific polymerase chain reaction primers. B. halotolerans QTH8 has a vital potential for the sustainable biocontrol of wheat crown rot.

Piperlongumine, a natural alkaloid substance extracted from the fruit of the long pepper ( Piper longum Linn .), is known to inhibit the cytosolic thioredoxin reductase (TXNRD1 or TrxR1) and selectively kill cancer cells. However, the details and mechanism of the inhibition by piperlongumine against TXNRD1 remain unclear. In this study, based on the classical DTNB reducing assay, irreversible inhibition of recombinant TXNRD1 by piperlongumine was found and showed an apparent k inact value of 0.206 × 10 -3 µM -1 min -1 . Meanwhile, compared with the wild-type TXNRD1 (-GCUG), the UGA-truncated form (-GC) of TXNRD1 was resistant to piperlongumine, suggesting the preferential target of piperlongumine is the selenol (-SeH) at the C-terminal redox motif of the enzyme. Interestingly, the high concentration of piperlongumine-inhibited TXNRD1 showed that its Sec-dependent activity is decayed but its intrinsic NADPH oxidase activity is retained. Furthermore, piperlongumine did not induce ferroptosis in HCT116 cells at 10 µM, whereas significantly promoted erastin-induced lipid oxidation, which could be alleviated by supplying glutathione (GSH) or N-acetyl L-cysteine (NAC). However, restricting GSH synthesis by inhibiting glutaminase (GLS) using the small molecule inhibitor CB-839 only slightly enhanced erastin-induced cell death. Taken together, this study elucidates the molecular mechanism of the antitumor capacity of piperlongumine by targeting TXNRD1 and reveals the potential possibility of inhibiting TXNRD1 to strengthen cancer cells' ferroptosis.

An important area in a gathering place is a region attracting the constant attention of people and has evident visual features, such as a flexible stage or an open-air show. Finding such areas can help security supervisors locate the abnormal regions automatically. The existing related methods lack an efficient means to find important area candidates from a scene and have failed to judge whether or not a candidate attracts people's attention. To realize the detection of an important area, this study proposes a two-stage method with a novel multi-input attention network (MAN). The first stage, called important area candidate generation, aims to generate candidate important areas with an image-processing algorithm (i.e., K-means++, image dilation, median filtering, and the RLSA algorithm). The candidate areas can be selected automatically for further analysis. The second stage, called important area candidate classification, aims to detect an important area from candidates with MAN. In particular, MAN is designed as a multi-input network structure, which fuses global and local image features to judge whether or not an area attracts people's attention. To enhance the representation of candidate areas, two modules (i.e., channel attention and spatial attention modules) are proposed on the basis of the attention mechanism. These modules are mainly based on multi-layer perceptron and pooling operation to reconstruct the image feature and provide considerably efficient representation. This study also contributes to a new dataset called gathering place important area detection for testing the proposed two-stage method. Lastly, experimental results show that the proposed method has good performance and can correctly detect an important area.

Thioredoxin reductase (TrxR) is one class of the most important antioxidant selenoproteins and is involved in regulating tumor genesis and progression. It has been reported that naphthoquinones can target and inhibit TrxR1 activity therefore produce reactive oxygen species (ROS) mediated by TrxR1, resulting into cellular redox imbalance and making the naphthoquinone compounds to become potential antitumor chemotherapy drugs. The purpose of this work is to explore the interaction between TrxR1 and menadione using biochemical and mass-spectrometric (MS) analyses, to further reveal the detailed mechanisms of TrxR1-mediated naphthoquinone reduction and inhibition of TrxR1 by naphthoquinone compounds. Using the site-directed mutagenesis and recombinantly expressed TrxR1 variants, we measured the steady-state kinetic parameters of menadione reduction mediated by TrxR1 and its variants, performed the inhibition analysis of menadione on TrxR1 activity, and eventually identified the interaction between menadione and TrxR1 through MS analysis. We found that Sec-to-Cys mutation at residue of 498 significantly enhanced the efficiency of TrxR1-mediated menadione reduction, though the Sec⁴⁹⁸ is capable to catalyze the menadione reduction, indicating that TrxR1-mediated menadione reduction is dominantly in a Se-independent manner. Mutation experiments showed that Cys⁴⁹⁸ is mainly responsible for menadione catalysis in comparison to Cys⁴⁹⁷, while the N-terminal Cys⁶⁴ is slightly stronger than Cys⁵⁹ regarding the menadione reduction. LC-MS results detected that TrxR1 was arylated with one molecule of menadione, suggesting that menadione irreversibly modified the hyper-reactive Sec residue at the C-terminus of selenoprotein TrxR1. This study revealed that TrxR1 catalyzes the reduction of menadione in a Se-independent manner meanwhile its activity is irreversibly inhibited by menadione. Hereby it will be useful for the research and development of naphthoquinone anticancer drugs targeting TrxR1.

Tubulins are the proposed target of clinically relevant anticancer drugs, anthelmintic, and fungicide. β2-tubulin of the plant pathogen Fusarium graminearum was considered as the target of benzimidazole compounds by homology modeling in our previous work. In this study, α1-, α2-, and β2-tubulin of F. graminearum were produced in Escherichia coli. Three benzimidazole compounds (carbendazim, benomyl, and thiabendazole) interacted with the recombinant β2-tubulin and reduced the maximum fluorescence intensity of 2 μM β2-tubulin 47, 50, and 25%, respectively, at saturation of compound-tubulin complexes. Furthermore, carbendazim significantly inhibited the polymerization of α1-/β2-tubulins and α2-/β2-tubulins 90.9 ± 0.4 and 93.5 ± 0.05%, respectively, in vitro. A similar result appeared with benomyl on the polymerization of α1-/β2-tubulins and α2-/β2-tubulins at 89.9 ± 0.1% and 92.6 ± 1.2% inhibition ratios, respectively. In addition, thiabendazole inhibited 81.6 ± 1% polymerization of α1-/β2-tubulins, whereas it had less effect on α2-/β2-tubulin polymerization, with 20.1 ± 1.9% inhibition ratio. However, the three compounds cannot destabilize the polymerized microtubule. To illuminate the issue, mapping the carbendazim binding sites and β/α subunit interface on β/α-tubulin complexes by homology modeling showed that the two domains were closed to each other. Understanding the nature of the interaction between benzimidazole compounds and F. graminearum tubulin is fundamental for the development of tubulin-specific anti-F. graminearum compounds.

The mammalian selenoprotein thioredoxin reductase 1 (TrxR1) is a key enzyme in redox regulation, antioxidant defense, and cellular growth. TrxR1 can catalyze efficient reduction of juglone (5-hydroxy-1,4-naphthoquinone; walnut toxin) in a reaction which, in contrast to reduction of most other substrates of TrxR1, is not dependent upon an intact selenocysteine (Sec, U) residue of the enzyme. Using a number of TrxR1 mutant variants, we here found that a sole Cys residue at the C-terminal tail of TrxR1 is required for high-efficiency juglone-coupled NADPH oxidase activity of Sec-deficient enzyme, occurring with mixed one- and two-electron reactions producing superoxide. The activity also utilizes the FAD and the N-terminal redox active disulfide/dithiol motif of TrxR1. If a sole Cys residue at the C-terminal tail of TrxR1, in the absence of Sec, was moved further towards the C-terminal end of the protein compared to its natural position at residue 497, juglone reduction was, surprisingly, further increased. Ala substitutions of Trp407, Asn418 and Asn419 in a previously described "guiding bar", thought to mediate interactions of the C-terminal tail of TrxR1 with the FAD/dithiol site at the N-terminal domain of the other subunit in the dimeric enzyme, lowered turnover with juglone about 4.5-fold. Four residues of Sec-deficient TrxR1 were found to be easily arylated by juglone, including the Cys residue at position 497. Based upon our observations we suggest a model for involvement of the juglone-arylated C-terminal motif of TrxR1 to explain its high activity with juglone. This study thus provides novel insights into the catalytic mechanisms of TrxR1. One-electron juglone reduction by TrxR1 producing superoxide should furthermore contribute to the well-known prooxidant cytotoxicity of juglone., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the effectiveness of the modified Urbaniak operation to treat avascularnecrosis of the femoral head (ANFH)., Methods: A retrospective analysis was made on the clinical data of 38 patients (41hips) with ANFH treated between February 2010 and October 2012 with the modified Urbaniak operation (to add lateralfemoral incision based on femoral greater trochanter incision, to preserve the original fibula flap drilling, decompressionand filling through trochanteric outer cortex, and to select the descending branch of lateral circumflex femoral artery asthe supply vessel). Of 38 cases, 25 were male (28 hips), 13 were female (13 hips), aged 16-52 years (mean, 34 years); therewere 19 cases (21 hips) of alcoholic ANFH, 9 cases (9 hips) of traumatic ANFH, 5 cases (6 hips) of hormone ANFH, and5 cases (5 hips) of idiopathic ANFH. The disease duration ranged from 10 months to 6 years (mean, 3.7 years). According to Ficat staging criteria, 24 hips were rated as stages II and 17 hips as stage III. The preoperative Harris hip scores were80.63 ± 5.02 and 77.06 ± 6.77 in patients at stage II and III respectively. The related complications were recorded afteroperation. According to the findings of postoperative X-ray films, 4 grades were improvement, stabilization, deterioration,and failure; improvement or stabilization was determined to radiological success. According to the Harris score toevaluate the function of hips, more than 80 was determined to clinical success., Results: Healing by first intention wasachieved in all patients after operation. Three cases had numbness and hypoaesthesia of the lateral femoral skin, 1 case had abnormal sensation of the dorsal foot, which had no effect on daily life. Thirty-eight cases (41 hips) were followed up 1 year to 3 years and 3 months (mean, 2 years and 3 months). There was no complication such as hip joint stiffness, hip or groin persistent pain, hip joint infection, or ankle instability. At last follow-up, the X-ray films showed improvement in 23 hips (56.1%), stabilization in 17 hips (41.5%), and deterioration in 1 hip (2.4%); 40 hips obtained the radiological success. According to the Harris score, the results were excellent in 17 hips, good in 20 hips, fair in 3 hips, and poor in 1 hip with an excellent and good rate of 90.2%; 37 hips achieved the clinical success. The Harris scores were 89.92 ± 4.12 and 86.53 ± 5.70 in patients at stage II and III respectively at last follow-up, showing significant differences when compared with preoperative ones (t = 7.011, P = 0.000; t = 4.412, P = 0.000)., Conclusion: The modified Urbaniak operation has the advantages of more convenient operation, less complications, higher safety, and better hip functional recovery. It is effective method to treat ANFH.

Thioredoxin-related protein of 14 kDa (TRP14, also called TXNDC17 for thioredoxin domain containing 17, or TXNL5 for thioredoxin-like 5) is an evolutionarily well-conserved member of the thioredoxin (Trx)-fold protein family that lacks activity with classical Trx1 substrates. However, we discovered here that human TRP14 has a high enzymatic activity in reduction of l-cystine, where the catalytic efficiency (2,217 min(-1)⋅µM(-1)) coupled to Trx reductase 1 (TrxR1) using NADPH was fivefold higher compared with Trx1 (418 min(-1)⋅µM(-1)). Moreover, the l-cystine reduction with TRP14 was in contrast to that of Trx1 fully maintained in the presence of a protein disulfide substrate of Trx1 such as insulin, suggesting that TRP14 is a more dedicated l-cystine reductase compared with Trx1. We also found that TRP14 is an efficient S-denitrosylase with similar efficiency as Trx1 in catalyzing TrxR1-dependent denitrosylation of S-nitrosylated glutathione or of HEK293 cell-derived S-nitrosoproteins. Consequently, nitrosylated and thereby inactivated caspase 3 or cathepsin B could be reactivated through either Trx1- or TRP14-catalyzed denitrosylation reactions. TRP14 was also, in contrast to Trx1, completely resistant to inactivation by high concentrations of hydrogen peroxide. The oxidoreductase activities of TRP14 thereby complement those of Trx1 and must therefore be considered for the full understanding of enzymatic control of cellular thiols and nitrosothiols.

The ultralong strontium- (Sr-) substituted hydroxyapatite (SrHAp) whiskers were successfully prepared using acetamide as homogeneous precipitation reagent. The effect of the Sr substitution amount on the lattice constants and proliferation of human osteoblast cells (MG-63) was further investigated. The results showed that the SrHAp whiskers with diameter of 0.2-12 μm and ultralong length up to 200 μm were obtained and the Sr substitution level could be facilely tailored by regulating the initial molar ratio of Sr/(Sr + Ca) in raw materials. The Sr(2+) replaced part of Ca(2+) and the lattice constants increased apparently with the increase of the Sr substitution amount. Compared with the pure HAp whiskers, the Sr substitution apparently stimulated the proliferation of MG-63 at certain extracted concentrations. Our study suggested that the obtained SrHAp whiskers might be used as bioactive and mechanical reinforcement materials for hard tissue regeneration applications.

The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP oxidation have focused on pathways that increase or decrease reactive oxygen species levels and thereby affect PTP oxidation. The processes involved in reactivation of oxidized PTPs remain largely unknown. Here the role of the thioredoxin (Trx) system in reactivation of oxidized PTPs was analyzed using a combination of in vitro and cell-based assays. Cells lacking the major Trx reductase TrxR1 (Txnrd1(-/-)) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged. Furthermore, in vivo-oxidized PTP1B was reduced by exogenously added Trx system components, whereas SHP2 oxidation remained unchanged. Trx1 reduced oxidized PTP1B in vitro but failed to reactivate oxidized SHP2. Interestingly, the alternative TrxR1 substrate TRP14 also reactivated oxidized PTP1B, but not SHP2. Txnrd1-depleted cells displayed increased phosphorylation of PDGF-β receptor, and an enhanced mitogenic response, after PDGF-BB stimulation. The TrxR inhibitor auranofin also increased PDGF-β receptor phosphorylation. This effect was not observed in cells specifically lacking PTP1B. Together these results demonstrate that the Trx system, including both Trx1 and TRP14, impacts differentially on the oxidation of individual PTPs, with a preference of PTP1B over SHP2 activation. The studies demonstrate a previously unrecognized pathway for selective redox-regulated control of receptor tyrosine kinase signaling.

Gloshedobin, a thrombin-like enzyme from the venom of Gloydius shedaoensis, is usually produced as inclusion bodies in Escherichia coli cell. In this work, gloshedobin was separately fused with three fusion partners NusA, GST, and TrxA at its N terminus and then was expressed as fusion proteins in E. coli. The results showed that the NusA was the most efficient fusion partner to improve the solubility of recombinant gloshedobin. The purified NusA-fused gloshedobin with an overall yield of 64.6% was resolved as one band in the SDS-PAGE gel with molecular mass of about 90 kDa. Both fibrinogen clotting and fibrinogenolytic activities were found for the recombinant product. The purified NusA-fused gloshedobin exhibited amidolytic activity of 506 U/mg under optimal conditions of pH of 8.0 and 40 degrees C. The inhibition study of NusA-fused gloshedobin by various inhibitors showed that serine protease inhibitors, phenylmethylsulphonyl fluoride, and N-tosyl-L: -phenylalanine chloromethyl ketone, strongly inhibited its admidolytic activity, whereas ethylenediaminetetraacetic acid as well as heparin and hirudin did not, suggesting that NusA-fused gloshedobin exhibited the same characteristics as the native form of gloshedobin. The strategy of this work may contribute to improve the soluble expression level of other thrombin-like enzymes from snake venom in E. coli.

Objective: To produce a new bone tissue engineered carrier through combination of xenograft bone (X) and sodium alginate (A) and to investigate the biological character of the cells in the carrier and the ability of bone-forming in vivo, so as to provide experimental evidence for a more effective carrier., Methods: BMSCs were extracted from 2-week-old New Zealand rabbits and the BMSCs were induced by rhBMP-2 (1 x 10(-8)mol/L). The second generation of the induced BMSCs was combined with 1% (V/W) A by final concentration of 1 x 10(5)/mL. After 4-day culture, cells in gel were investigated by HE staining. The second generation of the induced BMSCs was divided into the DMEM gel group and the DMEM containing 1% A group. They were seeded into 48 well-cultivated cell clusters by final concentration of 1 x 10(5)/mL. Seven days later, the BMP-2 expressions of BMSCs in A and in commonly-cultivated cells were compared. The second generation of the induced BMSCs was mixed with 2% A DMEM at a final concentration of 1 x 10(10)/mL. Then it was compounded with the no antigen X under negative pressure. After 4 days, cells growth was observed under SEM. Twenty-four nude mice were randomly divided into 2 groups (n = 12). The compound of BMSCs-A-X (experimental group) and BMSCs-X (control group) with BMSCs whose final concentration was 1 x 10(10)/mL was implanted in muscles of nude mice. Bone formation of the compound was histologically evaluated by Image Analysis System 2 and 4 weeks after the operation, respectively., Results: Cells suspended in A and grew plump. Cell division and nuclear fission were found. Under the microscope, normal proliferation, many forming processes, larger nucleus, clear nucleolus and more nuclear fission could be seen. BMP-2 expression in the DMEM gel group was 44.10% +/- 3.02% and in the DMEM containing 1% A group was 42.40% +/- 4.83%. There was no statistically significant difference between the two groups (P > 0.05). A was compounded evenly in the micropore of X and cells suspended in A 3-dimensionally with matrix secretion. At 2 weeks after the implantation, according to Image Analysis System, the compound of BMSCs-A-X was 5.26% +/- 0.24% of the total area and the cartilage-like tissue was 7.31% +/- 0.32% in the experimental group; the compound of BMSCs-X was 2.16% +/- 0.22% of the total area and the cartilage-like tissue was 2.31% +/- 0.21% in the control group. There was statistically significant difference between the two groups (P < 0.05). At 4 weeks after the operation, the compound of BMSCs-A-X was 7.26% +/- 0.26% of the total area and the cartilage-like tissue was 9.31% +/- 0.31% in the experimental group; the compound of BMSCs-X was 2.26% +/- 0.28% of the total area and the cartilage-like tissue was 3.31% +/- 0.26% in the control group. There was statistically significant difference between the two groups (P < 0.05)., Conclusion: The new carrier compounding A and no antigen X conforms to the superstructural principle of tissue engineering, with maximum cells load. BMSCs behave well in the compound carrier with efficient bone formation in vivo.

Objective: To investigate the effect of dexamethasone, recombinant human fibroblast growth factor (rhFGF) and recombinant human bone morphogenetic protein 2 (rhBMP-2) on the proliferation and differentiation of marrow stromal stem cells (MSCs) for their further application in tissue engineering., Methods: MSCs were isolated and cultured in vitro, and then exposed to different dose of dexamethasone (10(-8) mol/l, 10(-7) mol/L, 10(-6) mol/L), rhFGF (50 ng/ml, 200 ng/ml, 500 ng/ml) and rhBMP-2 (50 ng/ml, 500 ng/ml, 1000 ng/ml) respectively. The total protein and alkaline phosphatase (ALP) activity of each group was measured on 4th and 7th day., Results: Exposure of MSCs with 10(-6) mol/L dexamethasone inhibited protein synthesis without obvious effects on ALP expression. The application of rhFGF significantly promoted cell proliferation but inhibited ALP activity. In comparison, ALP expression was significantly enhanced by treatment of rhBMP-2 at concentration of 500 ng/ml, 1000 ng/ml., Conclusion: The exposure of dexamethasone as well as rhBMP-2 to MSCs with an appropriate concentration promotes osteogenic expression without reverse effects on cell proliferation, which indicates the great potential value in cell-based strategy of bone tissue engineering.

The mature gene of gloshedobin, a snake venom thrombin-like enzyme from the snake, Gloydius shedaoensis, was cloned and expressed in strain E. coli BL21 (DE3). Having been induced by IPTG, the recombinant gloshedobin was in both soluble and insoluble forms. To avoid inclusion body formation, expression was optimized at 25 degrees C. Furthermore, a 50% increase in solubilization of the target protein was obtained by adding 0.1 mM Mg2+ to the medium. The purified recombinant gloshedobin gave a 44 kDa band on SDS-PAGE gel.

Gloshedobin, a thrombin-like enzyme from the venom of Gloydius shedaoensis, was expressed in Escherichia coli using expression vector pET-32a(+). The gene was expressed under T7 promotor with a fusion partner of Thx.Tag and a 6xHis.Tag at its 5' terminal. After induction by IPTG for 6 h, the recombinant enzyme was expressed in the cytoplasm. Expression at 25 degrees C gave twice the amount of recombinant gloshedobin in cytoplasm than at 37 degrees C.

OBJECTIVE: To evaluate the role of MHC II expression in posttrauma immune disturbances and infections. METHODS: In experimental study, peritoneal macrophages were harvested from traumatized mice and treated with GM-CSF, Ia molecules were determined by flow cytometry. In 24 trauma patients, monocyte HLA-DR expression was measured by APAAP technique. RESULTS: Marked inhibition of MHC II molecule expression was found in both traumatized mice and patients. In traumatic patients with infection, the inhibition was more severe. Treatment with GM-CSF in mice partially restored the Ia expression. CONCLUSIONS: Inhibition of MHC II molecules plays an important role in postrauma immune disturbances. There is a close relationship between HLA-DR inhibition and clinical infections.