Meet the authors: Ying Lu, Donghoon Lee, and Yanan Zhu.

We talk to co-first authors Donghoon Lee and Yanan Zhu and co-corresponding author Ying Lu about their paper "Molecular mechanism for activation of the 26S proteasome by ZFAND5" (this issue of Molecular Cell), the challenges of the project, their scientific pathways, and the late Dr. Alfred Goldberg.

Molecular mechanism for activation of the 26S proteasome by ZFAND5.

Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5's AN1 Zn-finger domain interacts with the Rpt5 ATPase and its C terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Upon proteasome binding, ZFAND5 widens the entrance of the substrate translocation channel, yet it associates only transiently with the proteasome. Dissociation of ZFAND5 then stimulates opening of the 20S proteasome gate. Using single-molecule microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.

Neutral sphingomyelinase 2 is required for HIV-1 maturation.

HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.

Fungal-induced glycolysis in macrophages promotes colon cancer by enhancing innate lymphoid cell secretion of IL-22.

Incorporation of microbiome data has recently become important for prevention, diagnosis, and treatment of colorectal cancer, and several species of bacteria were shown to be associated with carcinogenesis. However, the role of commensal fungi in colon cancer remains poorly understood. Here, we report that mice lacking the c-type lectin Dectin-3 (Dectin-3-/- ) show increased tumorigenesis and Candida albicans burden upon chemical induction. Elevated C. albicans load triggered glycolysis in macrophages and interleukin-7 (IL-7) secretion. IL-7 induced IL-22 production in RORγt+ (group 3) innate lymphoid cells (ILC3s) via aryl hydrocarbon receptor and STAT3. Consistently, IL-22 frequency in tumor tissues of colon cancer patients positively correlated with fungal burden, indicating the relevance of this regulatory axis in human disease. These results establish a C. albicans-driven crosstalk between macrophages and innate lymphoid cells in the intestine and expand our understanding on how commensal mycobiota regulate host immunity and promote tumorigenesis.

Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome.

The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.

Halogen-bonding boosting the high performance X-ray imaging of organic scintillators.

Organic scintillators with efficient X-ray excited luminescence are essential for medical diagnostics and security screening. However, achieving excellent organic scintillation materials is challenging due to low X-ray absorption coefficients and inferior radioluminescence (RL) intensity. Herein, supramolecular interactions are incorporated, particularly halogen bonding, into organic scintillators to enhance their radioluminescence properties. By introducing heavy atoms (X = Cl, Br, I) into 9,10-bis(4-pyridyl)anthracene (BPA), the formation of halogen bonding (BPA-X) enhances their X-ray absorption coefficient and restricts the molecular vibration and rotation, which boosts their RL intensity. The RL intensity of BPA-Cl and BPA-Br fluorochromes increased by over 2 and 6.3 times compared to BPA, respectively. Especially, BPA-Br exhibits an ultrafast decay time of 8.25 ns and low detection limits of 25.95 ± 2.49 nGy s-1. The flexible film constructed with BPA-Br exhibited excellent X-ray imaging capabilities. Furthermore, this approach is also applicable to organic phosphors. The formation of halogen bonding in bromophenyl-methylpyridinium iodide (PYI) led to a fourfold increase in RL intensity compared to bromophenyl-methyl-pyridinium (PY). It suggests that halogen bonding serves as a promising and effective molecular design strategy for the development of high-performance organic scintillator materials, presenting new opportunities for their applications in radiology and security screening.

Enhanced Horizontal Dipole Orientation by Novel Penta-Helicene Anthracene-Based Host for Efficient Blue Fluorescent OLEDs.

Due to the relatively low photoluminescence quantum yield (PLQY) and horizontal dipole orientation of doped films, anthracene-based fluorescent organic light-emitting diodes (F-OLEDs) have faced a great challenge to achieve high external quantum efficiency (EQE). Herein, a novel approach is introduced by incorporating penta-helicene into anthracene, presented as linear-shaped 3-(4-(10-phenylanthracen-9-yl)phenyl)dibenzo[c,g]phenanthrene (BABH) and 3-(4-(10-(naphthalen-2-yl)anthracen-9-yl)phenyl)dibenzo[c,g]phenanthrene (NABH). These blue hosts exhibit minimal intermolecular overlap of π-π stacking, effectively suppressing excimer formation, which facilitates the effective transfer of singlet energy to the fluorescent dopant for PLQY as high as 90%. Additionally, the as-obtained two hosts of BABH and NABH have effectively demonstrated major horizontal components transition dipole moments (TDM) and high thermal stability with glass transitional temperature (Tg) surpassing 188 °C, enhancing the horizontal dipole orientation of their doped films to be 89% and 93%, respectively. The OLEDs based on BABH and NABH exhibit excellent EQE of 10.5% and 12.4% at 462 nm and device lifetime up to 90% of the initial luminance over 4500 h at 100 cd m-2, which has firmly established them as among the most efficient blue F-OLEDs based on anthracene to date to the best knowledge. This work provides an instructive strategy to design an effective host for highly efficient and stable F-OLEDs.

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Mitochondria-mediated ferroptosis induced by CARD9 ablation prevents MDSCs-dependent antifungal immunity.

BACKGROUND: Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive. METHODS: The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot. RESULTS: CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis. CONCLUSIONS: Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.

The Long COVID Symptoms and Severity Score: Development, Validation, and Application.

OBJECTIVES: The primary focus of this research is the proposition of a methodological framework for the clinical application of the long COVID symptoms and severity score (LC-SSS). This tool is not just a self-reported assessment instrument developed and validated but serves as a standardized, quantifiable means to monitor the diverse and persistent symptoms frequently observed in individuals with long COVID. METHODS: A 3-stage process was used to develop, validate, and establish scoring standards for the LC-SSS. Validation measures included correlations with other patient-reported measures, confirmatory factor analysis, Cronbach's α for internal consistency, and test-retest reliability. Scoring standards were determined using K-means clustering, with comparative assessments made against hierarchical clustering and the Gaussian Mixture Model. RESULTS: The LC-SSS showed correlations with EuroQol 5-Dimension 5-Level (rs = -0.55), EuroQol visual analog scale (rs = -0.368), Patient Health Questionnaire-9 (rs = 0.538), Beck Anxiety Inventory (rs = 0.689), and Insomnia Severity Index (rs = 0.516), confirming its construct validity. Structural validity was good with a comparative fit index of 0.969, with Cronbach's α of 0.93 indicating excellent internal consistency. Test-retest reliability was also satisfactory (intraclass correlation coefficient 0.732). K-means clustering identified 3 distinct severity categories in individuals living with long COVID, providing a basis for personalized treatment strategies. CONCLUSIONS: The LC-SSS provides a robust and valid tool for assessing long COVID. The severity categories established via K-means clustering demonstrate significant variation in symptom severity, informing personalized treatment and improving care quality for patients with long COVID.

Mechanochemical Synthesis of Cuprous Complexes for X-ray Scintillation and Imaging.

Cuprous complex scintillators show promise for X-ray detection with abundant raw materials, diverse luminescent mechanisms, and adjustable structures. However, their synthesis typically requires a significant amount of organic solvents, which conflict with green chemistry principles. Herein, we present the synthesis of two high-performance cuprous complex scintillators using a simple mechanochemical method for the first time, namely [CuI(PPh3)2R] (R = 4-phenylpyridine hydroiodide (PH, Cu-1) and 4-(4-bromophenyl)pyridine hydroiodide (PH-Br, Cu-2). Both materials demonstrated remarkable scintillation performances, exhibiting radioluminescence (RL) intensities 1.52 times (Cu-1) and 2.52 times (Cu-2) greater than those of Bi4Ge3O12 (BGO), respectively. Compared to Cu-1, the enhanced RL performance of Cu-2 can be ascribed to its elevated quantum yield of 51.54%, significantly surpassing that of Cu-1 at 37.75%. This excellent luminescent performance is derived from the introduction of PH-Br, providing a more diverse array of intermolecular interactions that effectively constrain molecular vibration and rotation, further suppressing the nonradiative transition process. Furthermore, Cu-2 powder can be prepared into scintillator film with excellent X-ray imaging capabilities. This work establishes a pathway for the rapid, eco-friendly, and cost-effective synthesis of high-performance cuprous complex scintillators.

Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study.

PURPOSE: We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). METHOD: We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. RESULTS: Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). CONCLUSION: Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.

Effects of Sjogren's syndrome and high sugar diet on oral microbiome in patients with rampant caries: a clinical study.

OBJECTIVE: The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. PATIENTS AND METHODS: Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren's syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray-Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05). RESULTS: OTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries. CONCLUSION: Both salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries. CLINICAL RELEVANCE: This study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.

Trimethoprim-sulfamethoxazole prevents interstitial pneumonitis in B-cell lymphoma patients receiving chemotherapy: a propensity score matching analysis.

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.

Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study.

OBJECTIVES: To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population. METHODS: We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression. RESULTS: A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, p = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, p = 0.69), which does not provide evidence of the presence of horizontal pleiotropy. CONCLUSIONS: Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.

The natural compound Sanggenon C inhibits PRRSV infection by regulating the TRAF2/NF-κB signalling pathway.

Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease and one of the major causes of death in the global pig industry. PRRS virus (PRRSV) strains have complex and diverse genetic characteristics and cross-protection between strains is low, which complicates vaccine selection; thus, the current vaccination strategy has been greatly compromised. Therefore, it is necessary to identify effective natural compounds for the clinical treatment of PRRS. A small molecule library composed of 720 natural compounds was screened in vitro, and we found that Sanggenon C (SC) was amongst the most effective natural compound inhibitors of PRRSV infection. Compared with ribavirin, SC more significantly inhibited PRRSV infection at both the gene and protein levels and reduced the viral titres and levels of protein expression and inflammatory cytokine secretion to more effectively protect cells from PRRSV infection and damage. Mechanistically, SC inhibits activation of the NF-κB signalling pathway by promoting TRAF2 expression, thereby reducing PRRSV replication. In conclusion, by screening natural compounds, we found that SC suppresses PRRSV infection by regulating the TRAF2/NF-κB signalling pathway. This study contributes to a deeper understanding of the therapeutic targets and pathogenesis of PRRSV infection. More importantly, our results demonstrate that SC has potential as a candidate for the treatment of PRRS.

All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway.

BACKGROUND: M2-type macrophages are inflammation-suppressing cells that are differentiated after induction by cytokines such as IL-4 or IL-13, which play an important regulatory role in inflammation and influence the regression of inflammation-related diseases. All-trans retinoic acid (ATRA) has an important role in suppressing immune-mediated inflammatory responses but the effect and underlying mechanism of ATRA on the polarization of M2 macrophages remains unclear. METHODS: Macrophages were isolated from peritoneal wash fluid, and IL-4 (20 ng/mL) was used to construct a m2-type macrophage polarization model. The model was incubated with different concentrations of ATRA (15 µg/ml, 30 µg/ml, 45 µg/ml) for 24 h, and pretreated macrophages with p38MAPKα inhibitor SB202190 (20 µM). MTT, Trypan blue staining, Annexin V-PE/7-AAD staining, flow cytometry, real-time PCR and western blotting were used to investigate the effect and mechanism of ATRA on the polarization of M2 macrophages. RESULTS: Compared with the IL-4 group, the proportion of F4/80+CD206+ M2-type macrophages was significantly higher in the ATRA group (P < 0.01). mRNA and protein expression levels of Arg-1, IL-10 and TGF-ß1 were as significantly higher (P < 0.01) in the ATRA group as phosphorylation levels of STAT6 and p38MAPK (P < 0.01). After pretreatment with the addition of the inhibitor SB202190, M2-type macrophages proportion and their associated factors expression were significantly (P < 0.01) reduced, as compared with those in the ATRA group, but they were comparable (P > 0.05) with the IL-4 group. CONCLUSION: The combination of ATRA and IL-4 activated the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages.

Theoretical insights into the catalytic mechanism of propylene hydroformylation over Co-N-C materials.

M-N-C was recently reported to be a high activity catalyst for hydroformylation compared with a metal nanocluster. However, the nature of M-N-C sites and the dominant path of propylene hydroformylation on M-N-C sites with different structures are poorly understood. In this work, five different Co-N-C models (Co-N3-C, Co-N4-C, 0N-bridged Co2-N6-C, 1N-bridged Co2-N7-C and 2N-bridged Co2-N6-C) were constructed to simulate the Co active sites with different coordination that may exist on the surface of MOF-derived Co-based carbon materials. DFT combined with kinetic Monte Carlo (kMC) methods were used to study the catalytic performance for hydroformylation of different Co-N-C models. The results of the DFT calculations show that the coordination number and mode of N atoms could regulate the electronic density of the Co sites. The electronic density of the Co sites further affects the catalytic activity. The higher the electronic density is, the lower the energy barrier for partial hydrogenation of propylene and CO insertion reactions. Besides, the catalytic activity is also affected by the strong interaction in closer neighboring Co atoms in some Co2-Nx-C models. The strong interaction affects the adsorption state and energy of species, which also reduces the overall reaction energy barrier. The kMC simulation results further showed that the dominant path of propylene hydroformylation was the n-butylaldehyde path for the 0N-bridged model, and the isobutylaldehyde path for Co-N3-C and 2N-bridged models.

A Mechanistic Study of HZSM-5-Catalyzed Guaiacol Amination Using Photoionization Time-of-Flight Mass Spectrometry.

Thermal-catalytic conversion and amination (TCC-A) of lignin and lignin derivates over zeolites is a promising and renewable method to produce aromatic amines, but suffers from product diversity. Currently, no unambiguous mechanism could fully describe the chemistry of this process. In this work, the TCC-A mechanism of guaiacol, a typical lignin model compound, with ammonia over HZSM-5 was investigated by online photoionization time-of-flight mass spectrometry combined with density functional theory. Various products including amines, pyrroles, and pyridines were identified. The formation of methylamine and aminophenol below 400 °C via nucleophilic substitutions is attributed to the strong adsorption of ammonia on the active site of HZSM-5. Aniline is the major product above 400 °C coproduced with pyrroles and pyridines. It is suggested that the reactions among radical intermediates (•CH3 and •NH2) and molecules (guaiacol and catechol) lead to poor aniline selectivity via transmethylation, amination, and partial deoxygenation reactions. Hydroamination is proposed as the main formation mechanism of pyrroles and pyridines. The maximum yield of aniline can be achieved at 650 °C owing to the enhancement of amination and deoxygenation and the suppression of transmethylation reactions.

Prevalence of and factors associated with alexithymia among patients with chronic obstructive pulmonary disease in China: a cross-sectional study.

BACKGROUND: Alexithymia is a common psychological disorder. However, few studies have investigated its prevalence and predictors in patients with chronic obstructive pulmonary disease (COPD). Therefore, we aimed to determine the prevalence and predictors of alexithymia in Chinese patients. METHODS: This cross-sectional study included 842 COPD patients to assess the prevalence and predictors of alexithymia using the 20-item Toronto Alexithymia Scale (TAS-20). We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, the modified British Medical Research Council dyspnea Rating Scale (mMRC) to assess dyspnea, St. George's Respiratory Questionnaire (SGRQ) to assess quality of life, and the age-adjusted Charlson comorbidity index (ACCI) to assess comorbidities. Alexithymia-related predictors were identified using univariate and multivariate logistic regression analyses. RESULTS: The prevalence of alexithymia in COPD patients was 23.6% (199/842). Multivariate analysis showed that age [odds ratio (OR) 0.886; 95% confidence interval (CI) 0.794-0.998], body mass index (OR 0.879; 95% CI 0.781-0.989), HADS-anxiety (OR 1.238; 95% CI 1.097-1.396), HADS-depression (OR 1.178; 95% CI 1.034-1.340), mMRC (OR 1.297; 95% CI 1.274-1.320), SGRQ (OR 1.627; 95% CI 1.401-1.890), ACCI (OR 1.165; 95% CI 1.051-1.280), and GOLD grade (OR 1.296; 95% CI 1.256-1.337) were independent predictors for alexithymia in patients with COPD. CONCLUSIONS: The prevalence of alexithymia was high in Chinese COPD patients. Anxiety, depression, dyspnea, quality of life, comorbidities, and disease severity are independent risk factors, and age and BMI are predictive factors for alexithymia in COPD patients.