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Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

A mild Ru(0)-catalyzed cleavage of C(aryl)–O bonds enabled by a combination of a Ru3(CO)12 catalyst and an imine auxiliary is reported.

The mechanism and stereoselectivity of the Ni-catalyzed [3 + 3] annulation between donor–acceptor cyclopropanes (DACs) and diaziridines were rationalized by DFT calculations.

Racemate (rac-1) and conglomerate (cong-1) crystals show different phosphorescence behaviour. Rac-1 is a strong excitation-wavelength-tunable photoluminescent material; cong-1 exhibits white-light emission upon temperature change with a CIE 1931 coordinate of (0.33, 0.31).

Severe competition between nanolubricant additives and polar lubricating oil molecules for the formation of lubricant films has been hindering the progress of green and advanced lubricants. In this work, based on the tautomerism of cyanuric acid molecule (trione and triol configurations), two kinds of triazine-based covalent-organic frameworks (COFs), that is, Ton-COFs and Tol-COFs, were synthesized as additives of the polar PEG 400 oil, realizing compromise between them by providing delicate interactions. The triazine matrix bonding with intense polar groups in the framework of additives offers more powerful interactions to competitively form the adsorbed lubricant film on the surface of the metal substrate over PEG 400 oil and also bolts PEG 400 oil molecules by the hydrogen bonding inside the pore of the framework to cooperatively bear against the load. Molecular quantum chemical calculations further confirm that Ton-COFs can produce a more intense interaction with Fe atoms in the form of coordination and ions···π than Tol-COFs, far beyond PEG 400, and the cross-sectional profile of the worn surface definitely exhibits a protective lubricant film only composed of Ton-COFs. Consequently, at the low concentration of 0.3 wt %, the excellent friction reduction (41.2%) and antiwear property (97.4%) are achieved for the Ton-COFs compared to pure PEG 400 oil; moreover, 28.6% and 79.0% for Tol-COFs at the essential concentration of 0.7 wt % are achieved. This finding provides a novel insight from molecules to materials into guiding the development of additives for advanced lubricants.

At present, all kinds of computing models used in human society are based on statistics. Due to the large amount of data, conventional statistical methods cannot solve these problems well. In view of the concealment of data, the processing of large data plays a great role in the rational allocation of human resources, training professional talents, improving the operation of human resources, and improving the use and efficiency of human resources. This paper combines the method of human resource allocation based on recurrent neural network and conventional human resource allocation, in order to find a suitable method for personnel position selection and recommendation in the field of talent work. In terms of algorithm test, the F1 value of the proposed method is 0.823, which is 20.1% and 7.4% higher than the previous two methods, respectively, indicating that the method can effectively improve the hidden features, improve the training effect, and improve the performance of the model.

The present work focuses on a theoretical investigation of mechanistic features, chemoselectivity, regioselectivity, and effect of substituents in the gold-catalyzed reactions of alkynyl thioethers and isoxazoles. The DFT calculations reveal that the nucleophilic attack of isoxazole to a β

ObjectivesWe aim to investigate the genetic basis of a case of late-onset autoinflammatory disease characterised by arthritis, recurrent fever and skin rashes.MethodsWe performed whole-exome/genome sequencing and digital droplet PCR (ddPCR) to identify the pathogenic somatic mutation. We used single-cell RNA sequencing (scRNA-seq), intracellular cytokine staining, quantitative PCR, immunohistochemistry and western blotting to define inflammatory signatures and to explore the pathogenic mechanism.ResultsWe identified a somatic mutation inNLRC4(p.His443Gln) with the highest mosaicism ratio in the patient’s monocytes (5.69%). The somatic mutation resulted in constitutive NLRC4 activation, spontaneous apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) aggregation, caspase-1 hyperactivation and increased production of interleukin (IL)-1β and IL-18. Moreover, we demonstrated effective suppression of inflammatory cytokine production by targeting gasdermin D, an approach that could be considered as a novel treatment strategy for patients withNLRC4-associated autoinflammatory syndrome.ConclusionsWe reported a case of a late-onset autoinflammatory disease caused by a somaticNLRC4mutation in a small subset of leucocytes. We systemically analysed this condition at a single-cell transcriptomic level and revealed specific enhancement of inflammatory response in myeloid cells.

Since first developed, the conducting materials in wireless communication and electromagnetic interference (EMI) shielding devices have been primarily made of metal-based structures. Here, we present a graphene-assembled film (GAF) that can be used to replace copper in such practical electronics. The GAF-based antennas present strong anticorrosive behavior. The GAF ultra-wideband antenna covers the frequency range of 3.7 GHz to 67 GHz with the bandwidth (BW) of 63.3 GHz, which exceed ~110% than the copper foil-based antenna. The GAF Fifth Generation (5G) antenna array features a wider BW and lower sidelobe level compared with that of copper antennas. EMI shielding effectiveness (SE) of GAF also outperforms copper, reaching up to 127 dB in the frequency range of 2.6 GHz to 0.32 THz, with a SE per unit thickness of 6,966 dB/mm. We also confirm that GAF metamaterials exhibit promising frequency selection characteristics and angular stability as flexible frequency selective surfaces.

Capsaicin is a capsaicinoid in hot chili peppers, with excellent antibacterial and antimicrobial activities and a good safety profile, but its poor solubility and instability restrict its effectiveness. This limitation may be mitigated by encapsulation. Herein, capsaicin microcapsules (CCMs) were prepared through layer-by-layer self-assembly, using chitosan and carboxymethyl chitosan as shell materials. The chemical and microstructure structural characterization was evaluated by the methods of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The SEM indicated the microcapsules were irregular in shape with an average size of about 100 μm. The encapsulation had a high loading efficiency of 64.31%. FTIR and XRD revealed the absence of the interaction between the core and shell materials and the amorphous nature of the CCMs. The analysis results of the microcapsules’ release behavior showed the burst release of capsaicin in 7 days and a slow progression afterward in three solutions, with the highest release properties in a basic solution, followed by acidic and neutral salt solutions. The entomotoxicity of CCMs was conducted against Tribolium castaneum (Herbst), and its efficacy was compared with pure capsaicin. The CCMs were found to be highly effective against this pest. The LC50 value for capsaicin and its microcapsules was 31.37 and 29.75 mg/kg on adults, respectively. According to these values, T. castaneum’s development and reproduction were significantly inhibited compared with the control group. The excellent physicochemical characteristics and insecticidal performance show a high application value for integrated pest control.

Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function mutations in ADA2, characterized by systemic inflammation, vasculitis, immunodeficiency, and/or hematologic abnormalities. Methods: A retrospective analysis of patients with DADA2 diagnosed by whole exome sequencing at 17 rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype and treatment responses were analyzed.Results Thirty patients with DADA2 were enrolled in this cohort between January 2015 and December 2021. Median age at onset was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects in the cohort died from DADA2-related complications. The patients presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient with pure red cell aplasia (PRCA) and bone marrow failure (BMF) with variable cytopenia was observed in our cohort. Twenty-three (76.7%) patients received TNF inhibitors and all achieved clinical remission. Homozygous variants and compound heterozygous variants were identified in 5 and 25 patients, respective. Two patients received hematopoietic stem cell transplantation (HSCT), and both got remission. Among 39 unique variants in our cohort, six is novel.Conclusion: In order to establish the diagnosis early and prevent devastating clinical outcomes, genetic screening and/ or testing of adenosine deaminase enzymatic activity should be performed in patients with suspected clinical features. TNF inhibitors can be first line drug for patients with vasculitic DADA2. HSCT is an alternative choice for patients with refractory to TNF inhibitors or hematological disorders.

Background: Self-efficacy has been inconsistently operationalized in diabetes, with measures often failing to focus on confidence in one’s capacity to perform self-care. Measures that focus on confidence have been shown to be closely associated with self-care behaviors, but received limited psychometric evaluation and have not been examined in relation to diabetes distress. Methods: We examined the reliability and factor structure of a previously published 8-item scale evaluating self-efficacy for diabetes self-care activities adapted by Sarkar and colleagues in 2006. We assessed cross-sectional relationships in baseline data with overall diabetes self-care, medication adherence, and diabetes distress among 812 predominantly Latino adults with T2D. They participated in a self-management support trial (Female = 56.9%; Latino = 86.5%) ; Mean (SD) Age and A1C = 59.2 (10.8) , 9.3 (1.8) , respectively. Results: The scale demonstrated good internal reliability in the overall sample (α = .80) and among English (n = 179, α = .77) and Spanish (n = 633, α = .80) speakers. Exploratory factor analysis yielded a single factor, explaining 42% of the variance in self-efficacy scores. After adjusting for covariates, higher self-efficacy was independently associated with better diabetes self-care (β = .56, p < .001) , better medication adherence (β = .30, p < .001) , and lower diabetes distress (β = -.42, p < .001) . Moderation analyses suggested consistency in these relationships across age, gender, SES, language, health literacy and numeracy. Conclusions: To our knowledge, the factor structure of this diabetes self-efficacy scale has not been previously evaluated. Findings suggest self-efficacy is a robust correlate of T2D self-care, medication adherence, and distress. The scale is appropriate for predominantly disadvantaged English and Spanish speakers with varying health literacy and numeracy levels. Disclosure R.Fang: None. C.J.Hoogendoorn: None. L.D.Pappalardo: None. H.Mendez-rodriguez: None. E.A.Walker: None. J.S.Gonzalez: Consultant; Virta Health Corp. Funding National Institutes of Health (R18 DK098742) National Institutes of Health (RDK104845) National Institutes of Health (RDK121298) National Institutes of Health (RDK121896) Einstein-Mount Sinai Diabetes Research Center (P30 DK020541) New York Regional Center for Diabetes Translation Research (P30 DK111022)

Objectives: Diabetes self-efficacy (confidence in ability to perform diabetes self-care) and personal control (perceived ability to influence diabetes outcomes) have been associated with better T2D self-care and health outcomes. Social cognitive theory posits that both beliefs are necessary for optimal initiation and maintenance of behavior change. However, their independent effects are unclear in T2D, especially in relation to dietary behaviors. We examined the independent associations of self-efficacy and personal control with junk food dietary patterns (JFDP) among predominantly Latino and disadvantaged adults with T2D and explored potential mediating effects. Methods: Adults with T2D (N = 812; Age = 59.2 (10.8) ; F = 57%; A1C = 9.3 (1.8) ; Latino = 86%; Spanish-speakers = 78.0%) enrolled in a trial of telephonic self-management support, completed self-report measures of diet (Starting the Conversation-STC) , diabetes self-efficacy, and diabetes personal control at baseline. A 5-item JFDP sub-scale of the 8-item STC was supported by factor analysis. Results: Unlike personal control (r = 0.10, 95% CI = -0.06, 0.08) , self-efficacy was inversely correlated with JFDP (r = -0.16, 95% CI = -0.23, -0.10) . In multivariable analysis, higher self-efficacy had a small independent association with less JFDP (b = -0.02, SE = 0.003, 95% CI = -0.02, -0.01) but perceived control did not (b = -0.04, SE = 0.15, 95% CI = -0.35, 0.29) . Mediation analyses showed no evidence for personal control as a mediator of the relationship between self-efficacy and JFDP. Conclusion: Among a predominantly Latino, disadvantaged adults with sub-optimally controlled T2D, diabetes self-efficacy was associated with lower reported consumption of junk foods, whereas no effect was observed for personal control. If these associations reflect causal relationships, interventions aiming to reduce junk food consumption in this vulnerable population may have more of an impact by targeting self-efficacy beliefs. Disclosure H.Mendez-rodriguez: None. V.H.Jonas: None. L.D.Pappalardo: None. R.Fang: None. C.Schechter: None. E.A.Walker: None. C.J.Hoogendoorn: None. J.S.Gonzalez: Consultant; Virta Health Corp. Funding National Institute of Health's National Institute of Diabetes Digestive and Kidney Diseases (1R18DK098742-01A1)

Objectives: Physical symptoms (SXS) are commonly reported among adults with T2D and have a significant impact on functioning and self-management. Although there is evidence that symptom reporting is closely linked to the experience of negative affect (NA) , the directionality of this relationship remains unclear. This study used EMA to evaluate bidirectional temporal associations between SXS and NA in adults with sub-optimally controlled T2D. Methods: Adults with T2D (N = 61; Age = 55 (10) yrs; Women = 64.5%; Black = 61%; Latino = 36%; A1C = 8.5 (2.3) completed smartphone EMA of SXS and NA 3 x daily over a 14-day period. Linear mixed effect models were used to assess associations of total number of SXS reported (0-13) and subsequent levels of NA (0-5) , and vice-versa. Results: There were significant within- and between-person bidirectional associations between SXS and NA. Within-persons, a 1-point increase in SXS from one’s personal mean was associated with a 0.03-point increase in subsequent NA (95%CI: 0.01-0.04, p = .008) and a 1-point increase in NA from one’s personal mean was associated with a 0.39-point increase in subsequent SXS (95%CI: 0.27-0.50, p < .0001) . Between-persons, a 1-point increase in SXS personal mean was associated with a 0.18-point increase in subsequent NA (95%CI: 0.12-0.26, p < .0001) and a 1-point increase in one’s NA personal mean was associated with a 1.8-point increase in SXS (95%CI: 1.15-2.46, p < .0001) . Conclusion: Results showed bidirectional relations between SXS and NA, observed both within- and between-persons over the course of a day, among predominantly ethnic minority adults with T2D. If these patterns reflect causal associations, they suggest that interventions that reduce negative affect would also reduce the experience of physical symptoms, and vice versa. Given prior evidence linking these factors to self-management, functioning, and health outcomes in T2D, such interventions could have substantial impact. Disclosure S.R.Fishman: None. J.S.Gonzalez: Consultant; Virta Health Corp. C.J.Hoogendoorn: None. C.Wang: None. S.A.Mulvaney: None. V.H.Jonas: None. H.Mendez-rodriguez: None. R.Fang: None. C.A.Solon: None. J.P.Crandall: Research Support; Abbott Diabetes. Funding NIH P30 DK111022

Objective: Although following a healthy diet is a key aspect of diabetes self-care, few brief, validated dietary measures exist. The 8-item Starting the Conversation (STC) questionnaire shows promise but has limited validation, particularly among Latinos, who are disproportionately impacted by T2D. Methods: We assessed the STC’s factor structure in English and Spanish, convergent and divergent validity, and internal reliability at baseline using data from 812 predominantly Latino adults with T2D who participated in a trial of telephonic self-management support (Female = 56.9%; Latino = 85.8%; Mean (SD) Age and A1C = 59.2 (10.8) , 9.3 (1.8) , respectively) . We also examined the STC’s sensitivity to this intervention over 12 months. Results: Exploratory factor analysis yielded 2 factors: Junk Food and Healthy Food. When 3 items were excluded due to low loadings, a single Junk Food factor was retained, explaining 40% of variance in STC scores. Cronbach’s alphas for the 5-item Junk Food scale were similar in Spanish (α = .61) and English (α = .57) at baseline. The Junk Food scale demonstrated convergent validity with BMI (r = .13, p < .001) and self-reported diabetes self-care (r = -.33, p < .001) , but not with A1C (r = .04, p = .328) , systolic BP (r = -.09, p = .011) , or diastolic BP (r = -.04, p = .312) . Demonstrating divergent validity, the Junk Food scale did not correlate with 4 scales assessing beliefs about medication (rs ≤ .06; ps ≥ .103) . There was no significant difference in change in Junk Food scores over time between the intervention and control arms (DID = -.02, SE = .03, , 95% CI [-.08, .04]) . Conclusions: Although the Junk Food scale demonstrates mixed evidence for convergent validity, this 5-item measure may provide a useful assessment of unhealthy food consumption among English- and Spanish-speakers with T2D. To our knowledge, this is the first study to investigate the factor structure of the STC, which may inform its utility for research and practice. Disclosure L.D.Pappalardo: None. C.Schechter: None. R.Fang: None. C.J.Hoogendoorn: None. J.S.Gonzalez: Consultant; Virta Health Corp. E.A.Walker: None. Funding National Institutes of Health (R18 DK098742) Einstein–Mount Sinai Diabetes Research Center (P30 DK020541) New York Regional Center for Diabetes Translation Research (P30 DK111022)

A DFT study was carried out to investigate a zirconium-catalyzed hydroaminoalkylation of alkenes with N-silylated benzylamine. A global reactivity index (GRI) analysis showed that that substrates act as electrophiles while the active zirconaaziridine behaves as a nucleophile. Furthermore, the distortion/interaction analysis unveiled the role of the distortion and interaction energies in controlling the regioselectivity and diastereoselectivity when different alkene substrates are used. These results provide an in-depth analysis on how the substrate type influences the product selectivity.

The origin of chemoselectivity and the mechanism of the Au(I)-catalyzed [2,3]-sigmatropic rearrangement/cyclopropanation or C–H functionalization of diazoesters with allyl-functionalized sulfides, selenides, amines, or ethers as the second reactant were fully rationalized by density functional theory (DFT). The obtained results clearly indicate that the first step involves the formation of a gold carbene complex via the reaction of a Au(I) precursor with a diazoacetate substrate. In the major reaction pathway, the allyl-functionalized sulfides or selenides undergo a [2,3]-sigmatropic rearrangement via a free ylide intermediate. With an allyl amine as the second reactant, the main pathway is a selective para-C–H functionalization. However, an allyl ether as the second reactant mainly forms a cyclopropanation product through a concerted [2 + 1] cycloaddition reaction. Furthermore, the global reactivity index (GRI) analysis shows that the S or Se atoms of allyl sulfides or selenides possess a higher nucleophilicity index Nk compared to the O or N atoms of allyl ether or amine reactants, thus leading to distinct reaction pathways among the four model processes studied. In addition, the calculation results confirm that the [2,3]-sigmatropic rearrangement preferably occurs via a free ylide intermediate. This study provides novel synthetic possibilities and improves the reaction predictability when exploring the related types of Au-catalyzed organic transformations.

Location selection of emergency facilities is a vital issue in the disaster management, which can be considered as a multi-criteria decision making problem with uncertainty. In this regard, the evidential reasoning (ER) approach can be used for such a multiple criteria analysis with uncertain information. However, the original ER approach neither took into account the bounded rationality of experts, nor examined the information at different time nodes, which may not conform to the actual situation of location selection. To solve this problem, we propose a time-series-based ER approach under the bounded rationality of experts to make full use of all evidence. Firstly, we propose a prospect-theory-based modification function to adjust the evidence given by experts and reduce the corresponding subjectivity. Considering the information at different time, we then propose a time-series-based ER approach to generate the comprehensive evidence of each alternative over the whole period. Besides, a VIKOR-based ranking method is proposed to improve the way to rank alternatives in the original ER approach. Finally, the proposed method is applied in the location selection of the emergency material reserve and the corresponding comparative analyses are given to show the rationality of the proposed method.

To model and deal with complex decision-making problems, many methods have been proposed in the past decades. However, how to deal with probabilistic uncertainty is still an open question. In this regard, this paper introduces a prospect theory-based evidential reasoning (ER) approach to process such uncertainty in multi-expert multi-criteria decision-making. Firstly, we introduce a novel way to model the uncertainty by assigning the uncertain belief to the envelope of evidence, which makes the expression consistent with experts’ perceptions. The ER approach is used to aggregate individual decision-making matrices with probabilistic uncertainty to obtain a collective matrix. Then, the ER approach is applied again on the obtained collective matrix to aggregate the evaluations under different criteria to generate the comprehensive evaluation of each alternative. Given that the decision-maker may have different risk preferences to gain and loss from those of the experts, we introduce a prospect function of evaluation grades to rank alternatives. In this way, we can obtain the ranking of alternatives which considers both the evaluations of experts and the risk preference of the decision-maker. The advantages of this method are highlighted by a case study concerning the evaluation of sustainable development ability of enterprises.

This study analyzed the characteristics of 133 Haemophilus parasuis isolates in southern China. These isolates belonged to eleven serovars (1, 2, 4-10, 13 and 15) with 12.0% of them being characterised as non-typable. A relatively high level in resistance was encountered for trimethoprim + sulfamethoxazole (89.9%), tetracycline (75.3%), amoxicillin (69.1%), streptomycin (63.6%), carbenicillin (60.2%), kanamycin (46.6%) and ampicillin (45.6%). A total of 60% of the isolates were negative for group 1 virulence-associated autotransporters (vtaA). All group 1 vtaA negative isolates fell into polyacrylamide gel electrophoresis (PAGE) type I, while all group 1 vtaA positive isolates were classified as PAGE type II. The results of Multi-locus sequence typing (MLST) indicated a high degree of variation, 45 isolates in the study were assigned into 31 sequence types with 28 of these being new (not found in the MLST database). Antimicrobial resistance was observed in every serovar, there was no statistically significant correlation between the antimicrobial resistance and the serovars. The isolates allocated to clade 2 (based on MLST target sequences) showed the molecular characteristics of highly pathogenic strains in whole-cell protein profiling, vtaA groups 1, superoxide dismutase (sodA) sequence and MLST.

The flexible radio frequency (RF) wireless antennas used as sensors, which can detect signal variation resulting from the deformation of the antenna, have attracted increasing attention with the development of wearable electronic devices and the Internet of Things (IoT). However, miniaturization and sensitivity issues restrict the development of flexible RF sensors. In this work, we demonstrate the application of a flexible and highly conductive graphene-assembled film (GAF) for antenna design. The GAF with a high conductivity of 106 S/m has the advantages of light weight, high flexibility, and superb mechanical stability. As a result, a small-size (50 mm × 50 mm) and flexible GAF-based antenna operating at 3.13–4.42 GHz is achieved, and this GAF antenna-based wireless wearable sensor shows high strain sensitivities of 34.9 for tensile bending and 35.6 for compressive bending. Furthermore, this sensor exhibits good mechanical flexibility and structural stability after a 100-cycle bending test when attached to the back of the hand and the wrist, which demonstrates broad application prospects in health-monitoring devices, electronic skins, and smart robotics.

The mechanism, stereoselectivity, and regioselectivity in the Au- and Pt-catalyzed cycloadditions of indolyl-allenes were explored by density functional theory (DFT). Three different catalytic syst...

OBJECTIVE: To study the clinical features of children with colorectal polyps and the efficacy of endoscopic treatment. METHODS: A retrospective analysis was performed on the medical data of 1 351 children with colorectal polyps who were admitted and received colonoscopy and treatment in the past 8 years, including clinical features and the pattern and outcomes of endoscopic treatment. RESULTS: Among the 1 351 children, 893 (66.10%) were boys and 981 (72.61%) had an age of 2

Over the last 20 years, N-heterocyclic carbenes (NHCs) have emerged as a dominant direction in ligand development in transition metal catalysis. In particular, strong σ-donation in combination with tunable steric environment make NHCs to be among the most common ligands used for C–C and C–heteroatom bond formation. Herein, we report the study on steric and electronic properties of thiazol-2-ylidenes. We demonstrate that the thiazole heterocycle and enhanced π-electrophilicity result in a class of highly active carbene ligands for electrophilic cyclization reactions to form valuable oxazoline heterocycles. The evaluation of steric, electron-donating and π-accepting properties as well as structural characterization and coordination chemistry is presented. This mode of catalysis can be applied to late-stage drug functionalization to furnish attractive building blocks for medicinal chemistry. Considering the key role of N-heterocyclic ligands, we anticipate that N-aryl thiazol-2-ylidenes will be of broad interest as ligands in modern chemical synthesis.

Inflammation response is a complex physiological process and suppression of inflammation activated in macrophages induced by LPS is an important target for treatment of various chronic diseases. A crude extract produced by Streptomyces ssp. (R31 crude extract) which was isolated from a mangrove sediment showed a significant inhibitory effect in LPS-stimulated inflammatory response. In this study, R31 crude extract decreased the NO production dose-dependently. The release of IL-6 and IL-10 in macrophages were reduced upon pretreatment of R31 crude extract. In addition, R31 crude extract treatment inhibited the translocation of NF-κB and NFAT into the nucleus and the phosphorylation of MAPKs as well as AKT. On the other hand, R31 crude extract induced HO-1 expression in LPS-stimulated macrophage. Collectively, these findings indicate that R31 crude extract exhibited an anti-inflammatory effect and is a potential therapeutic candidate for the treatment of inflammatory diseases.

Mast cells are important immune cells that primarily localize in the interface between the host and external environment, and protect us from pathogen infection. However, they are also involved in the pathology of allergic diseases such as asthma and atopic dermatitis. A novel S phase kinase-associated protein 1 (SKP1) inhibitor 6-O-angeloylplenolin (6-OAP), was studied with its potential ability to alleviate the anti-IgE-induced inflammatory responses of primary human cultured mast cells (HCMCs) and LAD2 cell line.We isolated the HCMCs from the buffy coat of voluntary blood donors. The effects of 6-OAP on mast cell activation were evaluated by measuring degranulation, cytokine release, migration, calcium influx, and ERK phosphorylation using spectro-fluorescence assay, multiplex cytometric bead assay/ELISA, migration assay, Fluo-4 calcium flux assay, and western blot, respectively.It was found that 6-OAP exerted anti-inflammatory effects on human mast cells by dose-dependently suppressing the anti-IgE-mediated degranulation and release of cytokines such as proinflammatory cytokines (IL-8 and TNF-α), growth factors (GM-CSF, VEGF, and FGF), and chemokines (CCL2 and CCL3) in HCMC and LAD2 cells. It also suppressed the migration of immature HCMCs induced by CXCL12. Moreover, the process of calcium influx and ERK phosphorylation in activated HCMC cells were inhibited by 6-OAP administration.Our results showed that 6-OAP inhibited anti-IgE-induced inflammatory responses of human mast cells via suppressing calcium influx and ERK phosphorylation.

Over the last 20 years, N-heterocyclic carbenes (NHCs) have emerged as a dominant direction in ligand development in transition-metal-catalysis. In particular, strong σ-donation in combination with tunable steric environment make NHCs to be among the most common ligands used for C–C and C–heteroatom bond formation. Thus far, NHC ligand development has been almost exclusively limited to N-aryl-imidazolylidenes, such as IPr, prepared by deprotonation of symmetrical imidazolium salts. However, the molecular structure of imidazolylidene systems is constrained by the substitution with two nitrogen atoms, a limitation that prohibits the development of more active carbene 2 analogues. Herein, we report the first study on steric and electronic properties of thiazol-2-ylidenes. We demonstrate that the ring dissymmetry and enhanced 𝝅-electrophilicity result in a class of highly active carbene ligands for electrophilic cyclization reactions to form valuable oxazoline heterocycles. The evaluation of steric, electron-donating and 𝝅-accepting properties as well as structural characterization and coordination chemistry is presented. This mode of catalysis can be applied to late-stage drug functionalization to furnish attractive building blocks for medicinal chemistry. Considering the key role of N-heterocyclic ligands, we anticipate that N-aryl thiazol-2-ylidenes will be of broad interest as ligands in modern chemical synthesis.

The work was supported by the National Natural Science Foundation of China (71971145, 71771156, 72171158), the Andalusian Government under Project P20-00673, and also by the Spanish State Research Agency under Project PID2019-103880RB-I00/AEI/10.13039/501100011033., Risk assessment is a vital part in project management. It is possible that experts may provide comprehensive linguistic preference information in distinct forms with respect to different aspects of the risk assessment problem in investment management. It is a challenge to model and deal with comprehensive linguistic preference assessments in multiple forms given by experts. In this regard, this paper defines the generalised probabilistic linguistic preference relation (GPLPR) to represent different forms of linguistic preference information in a unified structure. Then, a probability cutting method is proposed to simplify the representation of a GPLPR. Afterwards, a graph-theory-based method is developed to improve the consistency degree of a GPLPR. A group decision making method with GPLPRs is then proposed to carry on the risk assessment in project management. Discussions regarding the comparative analysis and managerial insights are given., National Natural Science Foundation of China (NSFC) 71971145 71771156 72171158, Andalusian Government P20-00673, Spanish Government PID2019-103880RB-I00/AEI/10.13039/501100011033

Since first developed, the conducting materials in wireless communication and electromagnetic interference (EMI) shielding devices have been primarily made of metal-based structures. Here, we present a highly conductive and corrosion-resistant graphene assembled film (GAF) that can be used to fabricate multi-band 5G wireless communication electronics and EMI protection at frequencies ranging from tens of MHz to THz to demonstrate its potential in metal replacement in practical electronics. The GAF based antennas (dipole antenna, ultra-wideband antenna and 5G wireless communication antenna array) are comparable with metal-based antennas in terms of performance and device complexity. The EMI shielding effectiveness of GAF can reach up to 127 dB in the frequency range of 2.6 GHz - 0.32 THz, and a maximum shielding effectiveness per unit thickness is of 6966 dB/mm. Furthermore, the GAF metamaterials exhibit promising frequency selection characteristics and angular stability as flexible frequency selective surfaces that can work at 3.5 GHz and 60 GHz respectively.

Description, Deubiquitination of proteasome subunits by OTULIN regulates type I IFN production., OTULIN is a linear deubiquitinase that negatively regulates the nuclear factor κB (NF-κB) signaling pathway. Patients with OTULIN deficiency, termed as otulipenia or OTULIN-related autoinflammatory syndrome, present with early onset severe systemic inflammation due to increased NF-κB activation. We aimed to investigate additional disease mechanisms of OTULIN deficiency. Our study found a remarkable activation of type I interferon (IFN-I) signaling in whole blood, peripheral blood mononuclear cells, monocytes, and serum from patients with OTULIN deficiency. We observed similar immunologic findings in OTULIN-deficient cell lines generated by CRISPR. Mechanistically, we identified proteasome subunits as substrates of OTULIN deubiquitinase activity and demonstrated proteasome dysregulation in OTULIN-deficient cells as the cause of IFN-I activation. These results reveal an important role of linear ubiquitination in the regulation of proteasome function and suggest a link in the pathogenesis of proteasome-associated autoinflammatory syndromes and OTULIN deficiency.

Cohesive non-swelling soil (CNS) cushion technology is widely used to solve swelling deformation problems in expansive soil areas. However, the swelling inhibition mechanism is still not fully understood. In this study, the inhibition effect on expansive soil using a CNS layer was studied by performing five types of laboratory model tests under unidirectional seepage. The results showed that CNS cushion technology produced a sound inhibition effect on the swelling characteristics of expansive soil. It was shown that the cations in the CNS layer moved downward and accumulated on the surface of solids and produced an electrical environment inside the expansive soil. In this process, the adsorbed hydrated cations participated in ion exchange with the expansive soil, leading to the modification effect on its swelling potential. Meanwhile, the adsorbed water membrane surrounding the expansive soil aggregates formed by the hydrated cations obstructed further adsorption of water molecules, which inhibited the swelling development of expansive soil. Therefore, the swelling inhibition mechanism can be attributed to three factors: (i) modification effect, (ii) electrical environment, and (iii) deadweight of the CNS layer. The combined contribution of modification effect and electrical environment can be considered as an electric charge effect, which mainly controls the swelling characteristics of expansive soil. Keywords: Cohesive non-swelling soil (CNS), Expansive soil, Unidirectional seepage, Electric charge effect, Swelling inhibition mechanism

The first total synthesis of the Euphorbia diterpenoid pepluanol B in both racemic and enantioenriched form involves 20 steps from a known bicyclic diol. This synthesis features an unprecedented bromo-epoxidation to control the eight-membered-ring conformation. In addition, salient reactions for the construction of the tetracyclic backbone include a sterically challenging aldol reaction to establish the quaternary center, a ring closing metathesis (RCM) to forge the eight-membered ring, and a diastereoselective cyclopropanation to assemble the embedded cyclopropane motif.

The present work focuses on a theoretical investigation of the plausible mechanism, determination of catalytically active species, and understanding of the regioselectivity in the InCl3-catalyzed cycloaddition of N-tosyl formaldimine with alkenes or allenes. InCl3 and InCl2+ coordinated by dichloroethane (InCl2+-DCE) were investigated as model catalytic systems. DFT data supported that InCl2+-DCE represent the plausible in situ generated catalytic species. The catalytic cycle starts from the coordination of N-tosyl formaldimine to InCl2+-DCE, generating an In-complexed iminium intermediate. This then undergoes intermolecular reaction (aza-Prins) with alkene substrate to form a carbocation intermediate, which is chemoselectively attacked by the second N-tosyl formaldimine molecule to form a formaldiminium intermediate. In a final step, this intermediate undergoes the ring closure, leading to hexahydropyrimidine along with the regeneration of catalyst. In addition, our DFT results indicate that N-tosyl formaldimine not only acts as a reactant but also accelerates the 1,3-H-shift as a proton acceptor, giving an experimentally observed allylamide product. Also, the "iminium/alkene/imine" path was supported by calculation results for diastereoselective [2 + 2 + 2] reaction using an internal alkene. Finally, the regioselectivity of the InCl3-catalyzed cycloaddition using allenes along with N-tosyl formaldimine was also analyzed.

A strategy for the synthesis of 2,3-disubstituted indoles from 2-allyl-2-(2-nitrophenyl)cyclohexane-1,3-dione has been developed. A wide array of 2,3-disubstituted indoles were accessed in modest to good yields via a tandem reduction/condensation/fragmentation/cyclization sequence. The utility of this strategy was exemplified in the formal syntheses of leucomidine A and goniomitine. The mechanism was confirmed by experiments and density functional theory (DFT) calculations. Differential fragmentation made the reaction more complicated.

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.

As a multi-criteria decision-making (MCDM) method, the evidential reasoning (ER) approach can deal with uncertainties that are resulted from the limited knowledge and experience of experts. Due to the lack of information in the decision-making process, experts usually cannot give quantitative evaluations, but can only express their views with linguistic terms. It is usually impossible for experts to give accurate linguistic terms since they may hesitate among several linguistic terms or interval ones. In addition, experts may have different preferences for different linguistic evaluations. To fully express the evaluations, the probability can be introduced to model the preferences of experts. In this study, we propose the generalized probabilistic linguistic term set (G-PLTS) to represent the evaluation information with various linguistic forms. Then, the ER approach is investigated in the environment with G-PLTSs. Besides, a gained and lost dominance score (GLDS) method is utilized to rank the alternatives, forming an integrated method, which we call the generalized probabilistic linguistic evidential reasoning (GPLER) approach, to solve the MCDM problems with several uncertainties. Finally, we apply this method to the screening of high-risk population of lung cancer to verify the effectiveness of the proposed method.Keywords: General probabilistic linguistic term set; evidential reasoning approach; gained and lost dominance score method; screening of high-risk population for lung cancer

In order to evaluate the traffic-load-induced cumulative deformation of road high liquid limit subgrade soil, a series of laboratory tests are performed to determine the physical and mechanical properties of high liquid limit soil. A cumulative deformation model is then developed with consideration of the effects of dynamic deviator stress, the number of repeated loadings, and the material properties of subgrade soil. Based on Lu’s vehicle-road-ground coupling model, the traffic-load-induced stress, which is very important in predicting cumulative settlement of the subgrade, is calculated explicitly. The layerwise summation method is used to evaluate the traffic-load-induced cumulative deformation. Moreover, a parametric study is conducted using numerical computation and the results show that the traffic-load-induced cumulative deformation is mainly generated from the shallow soil, and the additional dynamic load plays an important role in analyzing the traffic-load-induced settlement.

A cyclization of propargylic alcohols with tert-butyl nitrite at room temperature in air was achieved using Pd(OAc)2 as catalyst. The first reported 4-oxoisoxazoline N-oxides could be directly accessed from a range of multisubstituted propargylic alcohols in moderate to excellent yields under mild conditions. Density functional theory calculations indicated that the reaction proceeds through a palladium-catalyzed NO2 addition that efficiently generates a ketoxime radical, which eventually produces 4-oxoisoxazoline N-oxide.

The frost heave and thaw settlement caused by freeze-thaw cycles will seriously affect the engineering properties of soil. This paper attempts to comparatively investigate the deterioration effect of freeze-thaw cycles on the mechanical properties of compacted clay in closed and open systems. The specimens were frozen and thawed from the top to bottom in two systems. The moisture contents and deformations after freeze-thaw cycles were measured. Mechanical parameters of soil were examined through triaxial compression tests. Results show that the moisture content and deformation of soil change evidently with the increase of freeze-thaw cycles in the open system, while these parameters in the closed system change little. In the open system, the attenuation rate of failure strength, elastic modulus, and angle of internal friction of soil subjected to 7 freeze-thaw cycles are all about 2 times as large as that in the closed system and the attenuation rate of cohesion is even 4 times of that in the closed system. These differences reveal that the deterioration effect of freeze-thaw cycles on soil strength is aggravated after water supply. These findings indicate that soil structure damage and moisture content increase is the dominant factor affecting engineering properties of the soil in the open system.