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A data-driven energy scan in the immediate vicinity of the τ pair production threshold has been performed using the Beijing Spectrometer at the Beijing Electron-Positron Collider. Approximately 5pb-1 of data, distributed over 12 scan points, have been collected. A previous mass value for the τ lepton, obtained using only the eµ final state, has been published. In this paper, the final BES result on the mass measurement is presented. The analysis is based on the combined data from the ee, eµ, eh, µµ, µh, and hh final states, where h denotes a charged Π or K. A maximum likelihood fit to the τ pair production cross section data yields the value mT=1776.96-0.21 -0.17+0.18+0.25. © 1995 The American Physical Society.

A data-driven energy scan in the immediate vicinity of the τ pair production threshold has been performed using the Beijing Spectrometer at the Beijing Electron-Positron Collider. Approximately 5pb-1 of data, distributed over 12 scan points, have been collected. A previous mass value for the τ lepton, obtained using only the eµ final state, has been published. In this paper, the final BES result on the mass measurement is presented. The analysis is based on the combined data from the ee, eµ, eh, µµ, µh, and hh final states, where h denotes a charged Π or K. A maximum likelihood fit to the τ pair production cross section data yields the value mT=1776.96-0.21 -0.17+0.18+0.25. © 1995 The American Physical Society.

The Beijing Spectrometer (BES) experiment has observed purely leptonic decays of the Ds meson in the reaction e+e-→Ds+Ds- at a c.m. energy of 4.03 GeV. Three events are observed in which one Ds decays hadronically to φπ, K̄*0K, or K̄0K, and the other decays leptonically to μνμ or τντ. With the assumption of μ-τ universality, values of the branching fraction, B(Ds→μνμ)=(1.5-0.6-0.2+1.3+0.3)%, and the Ds pseudoscalar decay constant, fDs=(4.3-1.3-0.4+1.5+0.4)×102 MeV, are obtained. © 1995 The American Physical Society.

For the first time, the dominant magnetoelectric activity of ZIF-67-derived carbonaceous microparticles embedded with Co nanoparticles and distinctive magnetothermal effect of MIL-88B-derived Fe 3 O 4 nanocubes decorated on carbonaceous microrods, respectively, were explored to be controlled by the structure of the MOF-derived electrically conductive carbonaceous matrix and metal nanoparticles.

Background: Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes., Aim: To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment., Methods: Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort., Results: A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit., Conclusion: Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Intra-abdominal infection is a common complication of blunt abdominal trauma. Early detection and intervention can reduce the incidence of intra-abdominal infection and improve patients' prognoses. This study aims to construct a clinical model predicting postsurgical intra-abdominal infection after blunt abdominal trauma., Methods: This study is a retrospective analysis of 553 patients with blunt abdominal trauma from the Department of General Surgery of 7 medical centers (2011-2021). A 7:3 ratio was used to assign patients to the derivation and validation cohorts. Patients were divided into 2 groups based on whether intra-abdominal infection occurred after blunt abdominal trauma. Multivariate logistic regression and least absolute shrinkage and selection operator regression were used to select variables to establish a nomogram. The nomogram was evaluated, and the validity of the model was further evaluated by the validation cohort., Results: A total of 113 were diagnosed with intra-abdominal infection (20.4%). Age, prehospital time, C-reactive protein, injury severity score, operation duration, intestinal injury, neutrophils, and antibiotic use were independent risk factors for intra-abdominal infection in blunt abdominal trauma patients (P < .05). The area under the receiver operating curve (area under the curve) of derivation cohort and validation cohort was 0.852 (95% confidence interval, 0.784-0.912) and 0.814 (95% confidence interval, 0.751-0.902). The P value for the Hosmer-Lemeshow test was .135 and .891 in the 2 cohorts. The calibration curve demonstrated that the nomogram had a high consistency between prediction and practical observation. The decision curve analysis also showed that the nomogram had a better potential for clinical application. To facilitate clinical application, we have developed an online at https://nomogramcgz.shinyapps.io/IAIrisk/., Conclusion: The nomogram is helpful in predicting the risk of postoperative intra-abdominal infection in patients with blunt abdominal trauma and provides guidance for clinical decision-making and treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Objective: The objective of this study was to investigate the influence of mental abacus calculation training (MACT) on subliminal cognitive processes., Methods: Twenty children with intensive MACT (MACT group) and 20 children without MACT (non-MACT group) were selected. The two groups of children were matched in age, sex, handedness and academic grade. The participants were tested with subthreshold arithmetic priming task while their neural activities were recorded with a 32-channel electroencephalogram system., Results: We found that MACT changed the subliminal cognitive mechanism of computational processing, speeding up the computation. MACT affected the computational processing mode. Specifically, in the identification stage, both groups of children adopted the visual space processing mode, while in the computing stage, the MACT group adopted a visual space processing mode, but the non-MACT group adopted a semantic processing mode. Moreover, MACT improved children's executive functions., Conclusion: These results yielded insights into the effect of early abacus training on children's cognitive processing, providing a theoretical basis for the development and promotion of abacus training., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Represented is a CuX 2 - or I 2 -promoted ring-opening dual halogenation of cyclopropenones with saturated oxygen heterocycles, providing an efficient method for the synthesis of 3-haloacrylates. The ring-opening reaction enables the construction of two C-X (X = Cl, Br, or I) bonds and a C-O bond as well as the cleavage of two C-O bonds and a C-C bond in a single step. This protocol is highly atom economical, has an excellent substrate scope, and exhibits the ability for gram-scale reaction.

A facile method is disclosed for the synthesis of α-thio/selenocyanato ketones through regioselective C-H thio/selenocyanation of ketones. The advantages include the use of easily available starting materials, high efficiency, simple operation, and easy scale-up. Control experiments provide evidence that the reaction proceeded via a radical way, while kinetic isotope effect experiments reveal that the cleavage of the C-H bond serves as the rate-limiting step.

Objective: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. Methods: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. Results: We broke down the cohort into 4 groups according to blood (0.3×10 9 /L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. Conclusion: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

Objective: To investigate the clinical efficacy of acellular dermis matrix combined with cervical strap muscle (ADM-CSM) as a composite tissue flap for repairing the laryngeal defect after partial laryngectomy. Methods: The medical records of 33 patients with laryngeal cancer who were diagnosed and treated at the First Affiliated Hospital of Sun Yat-sen University from January 2014 to December 2016 were retrospectively reviewed. The patients consisted of 32 males and 1 female with age range from 39 to 76 years. Laryngeal defects were repaired with ADM-CSM in 14 patients (2 for supraglottic laryngeal cancer, 12 for glottic laryngeal cancer) and with CSM fascial flaps in 19 patients (3 for supraglottic laryngeal cancer, 16 for glottic laryngeal cancer). Kaplan-Meier method was used to calculate the 3-year overall survival and local control rate. The functions of voice and swallowing after operation were evaluated by voice handicap index-30 (VHI-30) and MD Anderson dysphagia inventory. Univariate logistic regression analysis, t -test, and Mann-Whitney U test were used to compare the variables between the two groups. Results: The incidence of laryngeal stenosis was 2/14 in ADM-CSM group and 4/19 in CSM group. In the ADM-CSM group, 3-year overall survival and local control rates were 92.9% and 85.7%, respectively. In the CSM group, 3-year overall survival and local control rates were 78.9% and 84.2%, respectively. The time of operation(3 h vs . 4 h, Z =193.5, P <0.05), time of retaining the feeding tube(14 d vs . 17 d, Z =206.0, P <0.05), and length of stay(18.5 d vs . 22.1 d, t =-2.62, P <0.05) in the ADM-CSM group were significantly less than those in the CSM group. The quality of voice in the CSM group was better than that in the ADM-CSM group (66.85±27.65 vs .45.80±23.19, t =2.19, P <0.05), while swallowing function in the ADM-CSM group was better than that in the ACSM group (80.00[60.00, 80.00] vs .60.00[40.00, 80.00], Z =48.0, P <0.05). Conclusion: ADM-CSM is user-friendly control and safe composite tissue flap for repairing the laryngeal defect after partial laryngectomy, with less scar hyperplasia and higher satisfaction of swallowing function after operation.

A straightforward and efficient method for the preparation of 2-aryl-2H-indazoles from ortho-alkyl substituted azoxybenzenes is presented. The reaction proceeds through base-catalyzed benzyl C-H deprotonation and cyclization to afford 2-aryl-2H-indazoles in good yields. This synthetic strategy can be applied to the construction of several fluorescent and bioactive molecules.

We report an Ag-catalyzed one-pot three-component reaction of alkynone o -methyloxime, element selenium, and boronic acid, providing a facile route to selenated isoxazole product. This protocol features high efficiency, wide substrate scope, and the use of selenium powder as the selenium source., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Reported is the AgNO 3 -catalyzed three-component reaction of alkynylaryl esters, selenium powder and ArB(OH) 2 , providing a facile entry to selenated isochromenones. This work highlights the use of selenium powder as a selenium reagent in the synthesis of selenated isochromenones for the first time., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ag2O-promoted ring-opening reactions of cyclopropenones with oximes is disclosed in this work, providing a direct route to 1,3-oxazinones. This method highlights a new reactivity of cyclopropenones which undergo 1,4-addition with oximes followed by β-carbon elimination to in situ generate a α-carbonyl ketene intermediate.

A highly efficient method is disclosed for the synthesis of 1,2-dichalcogen heterocycles via [3 + 2] cycloaddition of cyclopropenone derivatives and elemental chalcogens. Different from other cyclopropenone derivatives, cyclopropenselenones undergo unprecedented rearrangement with elemental sulfur. The features of this protocol include mild reaction conditions, high efficiency, excellent atom economy, gram-scale ability, and good regioselectivity.

Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal-ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.

Background: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication., Objective: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis., Methods: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation., Results: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 μg/ml., Conclusions: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel template-free Cp*Rh-based molecular Solomon link has been established through selection of the flexible ligand L as a linker and the half-sandwich rhodium(III) dinuclear fragment B1 as a rigid capping unit. Furthermore, we demonstrate that the self-assembly of the Solomon link based on the flexible ligand is both solvent- and concentration-dependent: the Solomon link is formed in concentrated methanolic solutions, whereas formation of a dinuclear trapezoidal rectangle is favored at low concentrations or in acetonitrile or DMF solutions. Remarkably, alteration of the solvent or concentration can promote a unique and dynamic interconversion between the two molecular species, accompanying conformational change of the ligand. The synthetic outcomes are supported by single-crystal X-ray diffraction analysis., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Presented in this paper is photoinduced hydroxylation of organic halides, providing a mild access to a range of functionalized phenols and aliphatic alcohols. These reactions generally proceed under mild reaction conditions with no need for a photocatalyst or a strong base and show a wide substrate scope as well as excellent functional group tolerance. This work highlights the unique role of NaI that allows a challenging transformation to proceed under mild reaction conditions.

A template-free Cp*Ir-based molecular Solomon link and an unusual trefoil knot induced by stacking interactions were realized via selection of the nonrigid dipyridyl ligand 4,4'-bis(pyridin-4-ylmethyl)-1,1'-biphenyl ( BpmBp ). In addition, a novel heterobimetallic tetranuclear (Ir III 2 + Ag I 2 ) complex featuring argentophilic interaction was synthesized in high yield. Remarkably, the reversible topological transformation between the Solomon link and an unusual trefoil knot can be achieved by utilizing the chemical reactivity of silver(I) ions under mild conditions, as demonstrated by a detailed X-ray crystallographic study.

Presented in this work is a novel methodology for the synthesis of selenated benzofurans (or benzothiophenes) via AgNO 2 -catalyzed radical cyclization of 2-alkynylanisoles (or 2-alkynylthioanisoles), Se powder, and arylboronic acids. This method enables the construction of a benzofuran (benzothiophene) ring, two C-Se bonds, and a C-O(S) bond as well as the cleavage of a C-O(S) bond in a single step. Preliminary mechanistic studies imply that the AgNO 2 -catalyzed cyclization proceeds via an aryl selenium radical intermediate.

Background: Eosinophilic inflammation is a major phenotype associated with poorly controlled disease in nasal polyp patients. The difference between systemic and local eosinophilia in relation to disease control is poorly understood., Objective: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp., Methods: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European position paper on rhinosinusitis and nasal polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities., Results: We broke down the cohort into 4 groups according to blood (0.3 ​× ​10 9 /L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia., Conclusion: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π-electron-deficient thiazolo[5,4-d]thiazole-derived ligand. We demonstrate that the formation of mono-rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half-sandwich Rh III and Ir III building blocks. Furthermore, a concentration effect or D-A stacking interaction between the pyrene guest and the thiazolo[5,4-d]thiazole-based ligand promotes a unique and reversible conversion between catenane structures and metalla-rectangles. The synthetic results are supported by single-crystal X-ray diffraction analysis., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Acute uncomplicated lower urinary tract infection (UTI) is one of the most common bacterial infections. Patients usually present with dysuria, urinary urgency, urinary frequency, and suprapubic pain or tenderness. Approximately 150 million people are diagnosed with UTI each year worldwide. The high recurrence rate of lower UTI is a common problem of clinical treatment. The misuse of antibiotics has led to the emergence of a number of resistant bacterial strains. Thus, traditional Chinese medicine is considered as an alternative option for treating acute uncomplicated lower UTI. Thus, this study aims to evaluate the efficacy and safety of Sanjin tablets (SJT) for the treatment of acute uncomplicated lower UTI, explore whether SJT can reduce or substitute the use of antibiotics, and reduce the recurrence rate in the treatment of acute uncomplicated lower UTI., Methods/design: In this study, a randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical study will be established. A total of 252 patients with acute uncomplicated lower UTI (syndrome of dampness-heat in the lower jiao) will be randomly allocated in the ratio of 1:1:1 to three groups: experimental group; control group 1; and control group 2. The experimental group receives Sanjin tablets plus levofloxacin tablets (LT) placebo; the control group 1 receives LT plus SJT placebo; and the control group 2 receives SJT plus LT on the first five days, SJT plus LT placebo on the last two days. Each group will be treated for seven days and followed-up 1-2 times. The primary outcome measures of effective rate and recurrence rate are symptoms. Secondary outcome measures of effective rate and recurrence rate are the urine leukocytes, bacteriology examination, and safety assessment. Outcomes will be assessed at baseline and after treatment., Discussion: This study protocol will provide the research data of efficacy and safety of SJT for the treatment of acute uncomplicated lower UTI. The first aim is to determine whether Sanjin tablets can reduce the use of antibiotics; the second aim is to determine whether Sanjin tablets can substitute the use of antibiotics. The recurrence rate will be assessed after cured to determine whether SJT can reduce the recurrence rate. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment., Trial Registration: ClinicalTrials.gov, NCT03658291 . Registered on 4 September 2018.

A series of supramolecular transformation cascades are presented here, employing ligand exchange reactions, concentration-dependent Borromean ring (BR) linking and unlinking, and inverse electron-demand Diels-Alder (IEDDA) reactions. The new family of template-free, tetrazine-edged BRs are constructed by using ligand exchange reactions, and their concentration-dependent linking and unlinking reactions have been observed. Moreover, Borromean precursors have been demonstrated to further undergo supramolecular structural transformations induced by rapid and efficient IEDDA reactions to afford corresponding post-assembly modified architectures. Remarkably, subtle steric increases of the pyridazine fragments obtained by IEDDA reactions is regarded to induce controlled topological transformations in the cascade, unlinking the Borromean structures by using electron-rich dienophiles as triggering signals.

A series of metallosupramolecular architectures have been prepared, including rectangles, prisms and cages, that feature half-sandwich rhodium(III) fragments at the vertices. Remarkably, a stable cage-like heteropolymetallic complex possessing eight rhodium(III) and two silver(I) metal ions (3) has been obtained following a multistep procedure. The Rh III /Ag I mixed macrocage enables the separation of dihalogenated benzene derivatives with high selectivity. Furthermore, a detailed X-ray crystallographic study confirmed that the discriminative encapsulation of para-dihalobenzene (dichlorobenzene, dibromobenzene and diiodobenzene) is favored by Ag-π interactions and steric effects., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A radical cascade cyclization of 2-alkynylthioanisoles with α-oxocarboxylic acids with AgNO3 has been described. This reaction provides a novel route to directly access 3-acylbenzothiophenes from simple chemical feedstocks. In particular, the utility of the approach was demonstrated by its application to the synthesis of a polymerization inhibitor and a raloxifene precursor.

Background: Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP., Methods: Samples were collected from 30 NP patients and 16 control subjects recruited prospectively. The mRNA expression of cytokines, including TSLP, IL-25 and IL-33, as well as interferon (IFN)-γ, IL-4, IL-5, IL-13 and IL-17A in NP and control tissues was examined by qualitative polymerase chain reaction (qPCR). The expression of IL-17RB, ST2 and TSLPR as well as other surface markers on myeloid DCs (mDCs) was examined by flow cytometry., Results: Increased numbers of total and activated mDCs were found in NP patients. mDCs demonstrated significantly higher expression of IL-17RB, ST2 and TSLPR than those in control tissues. The activated mDCs exhibited up-regulations of OX40L and ICOSL, but down-regulation of PDL1 in NP. Moreover, the IL-17RB, ST2 and TSLPR levels on mDCs were positively correlated with IL-25, IL-33 and TSLP mRNA levels, respectively, in NP. Furthermore, IL-17RB and ST2 expressions on mDCs were correlated with the IL-5 mRNA level as well as eosinophil number in NP. Importantly, the IL-17RB expression on mDCs and the OX40L expression on activated mDCs in NP were positively correlated with CT score and total nasal symptom score., Conclusions: Increased expressions of IL-17RB and ST2 on mDCs are associated with enhanced local Th2 inflammation in NP, suggesting that mDCs might play a role in IL-25- and IL-33-induced type 2 responses and eosinophilic inflammation in NP.

Background: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease (COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia tolerance., Methods: We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time (ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time (STT) and adjusted standard hypoxia tolerance time (ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, respectively., Results: Since mice were grouped according to either body weight (BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT method., Conclusion: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.

A novel metal-free reduction system, in which H 2 Se (or HSe - ) produced in situ from Se/DMF/H 2 O acts as the active reducing species, has been developed. By using water as an inexpensive, safe, and environmentally friendly surrogate as the hydrogen donor, this new reduction system incorporating Se/DMF/H 2 O displayed high selectivity and good activity in the reduction of α,β-unsaturated ketones and alkynes. Therefore, this reduction system has great potential to be a general and practical reduction methodology in organic transformation.

Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) represent a promising cell source for patient-specific cell therapy. We previously demonstrated that they display an immunomodulatory effect on allergic airway inflammation. Glucocorticoids are powerful anti-inflammatory compounds and widely used in the therapy of allergic diseases. However, the effect of glucocorticoids on the immunomodulatory function of iPSC-MSCs remains unknown. This study aimed to determine the effect of dexamethasone (Dex) on the immunomodulatory function of iPSC-MSCs in vitro and in vivo. A total of three human iPSC-MSC clones were generated from amniocyte-derived iPSCs. Anti-CD3/CD28-induced peripheral blood mononuclear cell (PBMC) proliferation was used to assess the effect of Dex on the immunoinhibitory function of iPSC-MSCs in vitro. Mouse models of contact hypersensitivity (CHS) and allergic airway inflammation were induced, and the levels of inflammation in mice were analyzed with the treatments of iPSC-MSCs and Dex, alone and combined. The results showed that Dex did not interfere with the immunoinhibitory effect of iPSC-MSCs on PBMC proliferation. In CHS mice, simultaneous treatment with Dex did not affect the effect of iPSC-MSCs on the inflammation, both in regional draining lymph nodes and in inflamed ear tissue. In addition, co-administration of iPSC-MSCs with Dex decreased the local expression of interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears of CHS mice. In the mouse model of allergic airway inflammation, iPSC-MSC treatment combined with Dex resulted in a similar extent of reduction in pulmonary inflammation as iPSC-MSCs or Dex treatment alone. In conclusion, Dex does not significantly affect the immunomodulatory function of iPSC-MSCs both in vitro and in vivo. These findings may have implications when iPSC-MSCs and glucocorticoids are co-administered.

Acute lung injury (ALI) is characterized by non-cardiogenic diffuse alveolar damage and often leads to a lethal consequence, particularly when hypoxia coexists. The treatment of ALI remains a challenge: pulmonary inflammation and hypoxia both contribute to its onset and progression and no effective prevention approach is available. Here, we aimed to investigate the underlying mechanism of hypoxia interaction with inflammation in ALI and to evaluate hypoxia-inducible factor 1 alpha (HIF-1α)-the crucial modulator in hypoxia-as a potential therapeutic target against ALI. First, we developed a novel ALI rat model induced by a combined low-dose of lipopolysaccharides (LPS) with acute hypoxia. Second, we used gene microarray analysis to evaluate the inflammatory profiles of bronchi alveolar lavage fluid cells of ALI rats. Third, we employed an alveolar macrophage cell line, NR8383 as an in vitro system together with a toll-like receptor 4 (TLR4) antagonist TAK-242, to verify our in vivo findings from ALI animals. Finally, we tested the therapeutic effects of HIF-1α augmentation against inflammation and hypoxia in ALI. We demonstrated that (i) LPS upregulated inflammatory genes, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), in the alveolar macrophages of ALI rats, which were further enhanced when ALI combined with hypoxia; (ii) hypoxia exposure could further enhance the upregulation of alveolar macrophageal TLR4 that was noticed in LPS-induced inflammatory ALI, conversely, TLR4 antagonist TAK-242 could suppress the macrophageal expression of TLR4 and inflammatory cytokines, including TNF-α, IL-1β, and IL-6, suggesting that the TLR4 signaling pathway as a central link between inflammation and hypoxia in ALI; (iii) manipulation of HIF-1α in vitro could suppress TLR4 expression induced by combined LPS and hypoxia, via suppressing promoter activity of the TLR4 gene; (iv) preconditioning augmentation of HIF-1α in vivo by HIF hydroxylase inhibitor, DMOG excreted protection against inflammatory, and hypoxic processes in ALI. Together, we see that hypoxia can exacerbate inflammation in ALI via the activation of the TLR4 signaling pathway in alveolar macrophages and predispose impairment of the alveolar-capillary barrier in the development of ALI. Targeting HIF-1α can suppress TLR4 expression and macrophageal inflammation, suggesting the potential therapeutic and preventative value of HIF-1α/TLR4 crosstalk pathway in ALI.

A series of bimetallic and trimetallic complexes has been prepared by N-alkylation of mononuclear half-sandwich rhodium and iridium di-NHC complexes featuring bidentate chelate ligands composed of a classical NHC and a C-azolato donor. The shape and the separation between metal centers in the obtained complexes are highly dependent on the alkylating agent used. While the polynuclear complexes were formed as diastereomeric mixtures according to NMR spectroscopy, X-ray diffraction analysis revealed their remarkable preference to crystallize as meso compounds. The reactivity of the bimetallic, olefin-bridged complexes in electrophilic addition reactions has been investigated.

Three aromatic ligands containing carboxyl- or nitrogen-substituted groups were employed in the construction of half-sandwich complexes via C-H activation-directed assembly, leading to the construction of eleven multinuclear organometallic iridium or rhodium complexes, including those of bi-, tetra-, hexa- and octanuclear, under mild conditions, with the help of N-donor linkers. These complexes were characterized by proton NMR, IR spectroscopy, elemental analysis, electrospray ionization (ESI) mass spectrometry and single-crystal X-ray diffraction analysis. In these complexes, two complexes were observed to exist as isomers, and several racemic enantiomers can be found. X-ray crystal structure determinations show that a series of supramolecular tunnel architectures are formed by stacking through hydrogen-bond interactions, and solvent or trifluoromethylsulfonate anion guests were found to be located in certain parts of the channels. This work represents the first successful construction of octanuclear half-sandwich complexes based on the cleavage of C-H bonds.

Although reversible photo-dimerization or oxygenation of anthracene and its derivatives is a common reaction, light-initiated reversible conversion of endoperoxide organometallic frameworks has only rarely been addressed. Herein, a series of tetranuclear organometallic macrocycles, [Cp* 2 Rh 2 (μ-C 2 O 4 -κO)] 2 (BP4VA) 2 (OTf) 4 (4), [Cp* 2 Rh 2 (BiBzIm)] 2 (BP4VA) 2 (OTf) 4 (5), and [Cp* 2 Rh 2 (DHBQ)] 2 (BP4VA) 2 (OTf) 4 (6), were obtained in good yields from the reactions of the binuclear half-sandwich rhodium precursors [Cp* 2 Rh 2 (μ-C 2 O 4 -κO)Cl 2 ] (1), [Cp* 2 Rh 2 (BiBzIm)Cl 2 ] (2), and [Cp* 2 Rh 2 (DHBQ)Cl 2 ] (3) with the 9,10-bis((E)-2-(pyrid-4-yl)vinyl)anthracene (BP4VA) ligand. The photochemical reaction of these metallarectangles was investigated by NMR and UV/vis spectroscopy. We have demonstrated that complexes 4, 5, and 6 can be reversibly and nearly quantitatively converted to the macrocyclic endoperoxides 4-O2, 5-O2, and 6-O2. Meanwhile, the structure of the endoperoxide photoproducts was unambiguously confirmed by 1 H/ 13 C NMR spectroscopy, IR spectroscopy, elemental analyses, and X-ray crystallography.

Template-free molecular Borromean rings (BRs) and open-ended molecular capsules were realized by strategic selection of the polypyridyl ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TPPHZ) with a large surface area and specific geometry. The topology of these intricate architectures was constructed via precisely controlled stacking interactions, as evidenced from single-crystal X-ray analysis.

Different types of multinuclear half-sandwich rhodium macrocycles and cages were designed and synthesized by using two similar multifunctional hydroxamate ligands (pyrazine-2-hydroxamic acid (NaHL 1 ) and 4,4'-bipyridine-2-hydroxamic acid (KHL 2 )) featuring one monodentate site and two pairs of chelating sites. The Rh III -Pd II heterometallic macrocycles were constructed by using the semi-open palladium(II) source [Pd(en)Cl 2 ] with two free acceptor sites. However, only one kind of macrocycle was found when the shorter ligand L 1 was used, while in for the larger ligand, various spectroscopic techniques demonstrated the coexistence of hexanuclear and octanuclear macrocycles in solution and the proportions of both components depended on concentration and temperature. The palladium salt Pd(NO 3 ) 2 , as a source of "naked" Pd 2+ , was introduced to assemble the cuboid-shaped cage composed of two types of metal ions and three types of organic ligands. In addition, two silver(I)-containing mixed-metal complexes bridged by pyrazine were obtained, in which two forms of decanuclear complex with C 2v and C 2h point symmetry cocrystallized-one is a polymeric structure and the other is a discrete cage. However, the third form, with D 2 point symmetry, was found in the larger cage., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein we describe how to take advantage of a multifunctional ligand to conveniently control the shapes and sizes of different types of discrete organometallic assemblies. Using a versatile ligand 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylate (HL 2- ), which features three kinds of chelating sites, together with half-sandwich rhodium fragments, a series of discrete organometallic complexes with tetranuclear parallelogram and hexanuclear trigonal prism shapes were achieved. The isomerization of the hexanuclear assemblies was confirmed by single-crystal X-ray diffraction analysis. The results also reiterate that pyridyl-substituted imidazole-4,5-dicarboxylate ligands can be used as multifunctional organic scaffolds in the construction of elegant architectures.

Background: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation., Objective: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance T H 2 responses., Methods: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c + monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4 + T cells, and cytokine production by these T cells was determined by intracellular flow cytometry., Results: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86 + mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86 + mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4 + T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4 + T cells to produce higher level of IL-4 but lower level of IFN-γ., Conclusion: Atopic IL-17RB + DCs can be up-regulated by LPS and promote a T H 2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs., Methods: Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production., Results: In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism., Conclusions: Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.

Background: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear., Methods: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro. Total RNA from the lungs and separated T cells were processed with an lncRNA/mRNA microarray. A series of bioinformatics technologies were used to screen the target lncRNAs., Results: iPSC-MSCs significantly prevented asthma inflammation and decreased the Th2 cytokine levels. Over 1300 lncRNAs were differentially expressed after the induction of asthma, and 846 or 4176 lncRNAs were differentially expressed with iPSC-MSC treatment in mice or in vitro, respectively. After overlapping the differentially expressed lncRNAs produced in a similar manner in mice and in vitro, 23 lncRNAs and 96 mRNAs were selected, in which 58 protein-coding genes were predicted to be potential targets of the 23 lncRNAs. Furthermore, using a series of bioinformatics technologies, 9 lncRNAs co-expressed with the most differentially expressed mRNAs, which were enriched in terms of the immune response, were screened out via Pearson's correlation coefficient with mRNAs that were involved with inflammatory cytokines and receptors. lncRNAs MM9LINCRNAEXON12105+ and AK089315 were finally emphasized via quantitative real-time PCR validation., Conclusions: Our results suggested that aberrant lncRNA profiles were present after asthma induction and iPSC-MSC treatment, suggesting potential targets of allergic inflammation and iPSC-MSC-mediated immunomodulation.

Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa.

Background: Chronic rhinosinusitis (CRS) is defined as a condition of inflammation in the paranasal sinus mucosa persisting for more than 12 weeks. We previously reported that the prevalence of CRS was about 8 % in China. Here, we aim to investigate the occupational and environmental risk factors associated with CRS., Methods: Data were collected from seven Chinese cities: Urumqi, Changchun, Beijing, Wuhan, Chengdu, Huaian and Guangzhou. CRS was diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP(3)OS) document. Participants were asked to complete a standardized questionnaire, which was developed by the Global Allergy and Asthma European Network (GA(2)LEN) project and covered sociodemographic characteristics, CRS-related symptoms and occupational and environmental exposures. We evaluated the association between CRS and various occupational and environmental factors using odds ratios (ORs) and 95 % confidence intervals (95 % CIs)., Results: The total study population consisted of 10,633 subjects, 850 (7.99 %) of whom were defined as having CRS according to the EP(3)OS criteria. We found that there were significant associations between occupational and environmental factors and CRS. Specifically, having a clearance-related job, occupational exposure to dust, occupational exposure to poisonous gas, a pet at home or carpet at home or at the workplace were risk factors for CRS. Additionally, the method used to keep warm in winter, the duration of time spent using air conditioning in summer and the frequency of exposure to mouldy or damp environments were significantly different in subjects with and without CRS., Conclusions: Our data showed that some occupational and environmental exposures are strongly associated with CRS, which aids in understanding the epidemiology of CRS.

Adult mesenchymal stem cells (MSCs) are immunoprivileged cells due to the low expression of major histocompatibility complex (MHC) II molecules. However, the expression of MHC molecules in human-induced pluripotent stem cells (iPSCs)-derived MSCs has not been investigated. Here, we examined the expression of human leukocyte antigen (HLA) in human MSCs derived from iPSCs, fetuses, and adult bone marrow (BM) after stimulation with interferon-γ (IFN-γ), compared their repair efficacy, cell retention, inflammation, and HLA II expression in immune humanized NOD Scid gamma (NSG) mice of hind limb ischemia. In the absence of IFN-γ stimulation, HLA-II was expressed only in BM-MSCs after 7 days. Two and seven days after stimulation, high levels of HLA-II were observed in BM-MSCs, intermediate levels were found in fetal-MSCs, and very low levels in iPSC-MSCs. The levels of p-STAT1, interferon regulatory factor 1, and class II transactivator exhibited similar phenomena. Moreover, p-STAT1 antagonist significantly reversed the high expression of HLA-II in BM-MSCs. Compared to adult BM-MSCs, transplanting iPSC-MSCs into hu-PBMNC NSG mice revealed markedly more survival iPSC-MSCs, less inflammatory cell accumulations, and better recovery of hind limb ischemia. The expression of HLA-II in MSCs in the ischemia limbs was detected in BM-MSCs group but not in iPSC-MSCs group at 7 and 21 days after transplantation. Our results demonstrate that, compared to adult MSCs, human iPSC-MSCs are insensitive to proinflammatory IFN-γ-induced HLA-II expression and iPSC-MSCs have a stronger immune privilege after transplantation. It may attribute to a better therapeutic efficacy in allogeneic transplantation., (© 2015 The Authors. STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)