Background and Aims
Due to their inherent characteristics, the function of group‐2 innate lymphoid cells (ILC2s) varies in a context‐dependent manner. ILC2s are involved in certain liver diseases; ...however, their involvement in HCC is unknown. In the present study, we assessed the role of an HCC‐derived ILC2 population in tumor progression.
Approach and Results
Through FACS and single‐cell RNA sequencing, we discovered that ILC2s were highly enriched in human HCC and correlated significantly with tumor recurrence and worse progression‐free survival as well as overall survival in patients. Mass cytometry identified a subset of HCC‐derived ILC2s that had lost the expression of killer cell lectin‐like receptor subfamily G, member 1 (KLRG1). Distinct from their circulating counterparts, these hepatic ILC2s highly expressed CD69 and an array of tissue resident–related genes. Furthermore, reduction of E‐cadherin in tumor cells caused the loss of KLRG1 expression in ILC2s, leading to their increased proliferation and subsequent accumulation in HCC sites. The KLRG1− ILC2 subset showed elevated production of chemotaxis factors, including C‐X‐C motif chemokine (C‐X‐C motif) ligand (CXCL)‐2 and CXCL8, which in turn recruited neutrophils to form an immunosuppressive microenvironment, leading to tumor progression. Accordingly, restoring KLRG1 in ILC2s, inhibiting CXCL2 in ILC2s, or depleting neutrophils inhibited tumor progression in a murine HCC model.
Conclusions
We identified HCC‐associated ILC2s as an immune regulatory cell type that promotes tumor development, suggesting that targeting these ILC2s might lead to new treatments for HCC.
Background and Purpose
Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro‐immune communication. Neuronal mechanism‐based therapeutic treatments remain ...lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro‐immune mechanism.
Experimental Approach
Pharmacological intervention, immunofluorescence, RNA‐sequencing, genetic modification and immunoassay were performed to dissect the neuro‐immune basis of itch and inflammation in atopic dermatitis‐like mouse model and in patients.
Key Results
Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)‐induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX‐314, a charged NaV blocker that enters through pathologically activated large‐pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV1.8‐expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1‐positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity‐dependent release of calcitonin gene‐related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model.
Conclusion and Implications
NaV1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti‐inflammatory and anti‐pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.
We have discovered a new flex‐activated mechanophore that releases an N‐heterocyclic carbene (NHC) under mechanical load. The mechanophore design is based upon NHC‐carbodiimide (NHC‐CDI) adducts and ...demonstrates an important first step toward flex‐activated designs capable of further downstream reactivities. Since the flex‐activation is non‐destructive to the main polymer chains, the material can be subjected to multiple compression cycles to achieve iterative increases in the activation percentage of mechanophores. Two different NHC structures were demonstrated, signifying the potential modularity of the mechanophore design.
A new kind of flex‐activated mechanophore, N‐heterocyclic carbene–carbodiimide adduct (NHC‐CDI), was developed as a platform to release different NHCs under mechanical load. The polymeric materials containing NHC‐CDI can be subjected to multiple compression cycles and successively release NHCs, which have potential to be utilized as self‐healing, self‐strengthening and self‐reporting materials.
In conventional mobile crowdsensing (MCS) applications, the crowdsensing server (CS-server) needs mobile users’ precise locations for optimal task allocation, which raises privacy concerns. This ...paper proposes a privacy-preserving task allocation framework (called P2TA) for edge computing enhanced MCS, focusing on optimize task acceptance rate while protecting participants’ privacy by introducing edge nodes. The basic idea is that edge nodes act as task assignment agents with privacy protection that prevents an untrusted CS-server from accessing a user’s private data. We begin with a thorough analysis of the limitations of typical task allocation and obfuscation schemes. On this basis, the optimization problem about location obfuscation and task allocation is formulated in consideration of privacy constraints, travel distance and impact of location perturbation. Through problem decomposition, the location obfuscation subproblem is modeled as a leader-follower game between the designer of location obfuscation mechanism and the potential attacker. Against inference attack with background knowledge, a genetic algorithm is introduced to initialize an obfuscation matrix. With the matrix, an edge node makes task allocation decisions that maximize task acceptance rate subject to differential and distortion privacy constraints. The effectiveness and superiority of P2TA compared to exiting task allocation schemes are validated via extensive simulations.
The design and research of luminescent and volatile organic compound (VOC) fluorescent sensing materials are of great significance and challenge. We report herein the ligand substitution reaction and ...VOC sensing of new heteroleptic Cu(P
˄
P)N
2
+
type copper(I) complexes. Firstly, three new complexes
1
–
3
were designed by utilizing a chelate diphosphine ligand 4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene (Xantphos) and synthesized by the substitution reaction of different N‐containing ligands of 4‐PBO (
1
), 3‐PBO (
2
), and 4,4′‐Bipy (
3
) (4‐PBO = 2‐(4′‐pyridyl)‐benzoxazole, 3‐PBO = 2‐(3′‐pyridyl)‐benzoxazole, 4,4′‐Bipy = 4,4′‐bipyridine), respectively. Three complexes were characterized by elemental analysis, spectroscopic analysis (IR, UV–Vis), single‐crystal X‐ray diffraction (SCXRD), and photoluminescence study. The SCXRD study revealed that complexes
1
and
2
both exhibit a molecular structure with tetrahedral copper(I) complex cation and hexafluorophosphate anion, while complex
3
differs in that its cation is a binuclear copper(I) structure bridged by 4,4′‐bipyridine. Three complexes
1
–
3
present supramolecular ribbon, supramolecular dimer, and supramolecular framework structure, respectively. Some differences of their UV–Vis absorption spectra were explained by TD‐DFT calculation and wavefunction analysis. It is found that
1
has an abnormal luminescence blue shift, and a luminescence mechanism through the high‐energy T
2
excited state is proposed by TD‐DFT calculation. Based on
3
, a fluorescent test strip was developed, and its fast and selective fluorescent sensing of pyridine vapor through quenching mechanism was successfully realized. The fluorescent quenching mechanism of the material was also studied, and it was proposed that the quenching should be attributed to the photoinduced electron transfer (PET) mechanism.
Three new heteroleptic Cu(NN)P2+ type cuprous complexes 1–3 were designed and synthesized by utilizing a diimine ligand 5‐methyl‐2‐(2′‐pyridyl)‐benzoxazole (MePBO) and different phosphine ligands ...PPh3 (1), m‐Tol3P (2) and POP (3), (PPh3=triphenylphosphine, m‐Tol3P=tris(3‐methylphenyl)phosphine, POP=bis2‐(diphenylphosphino)phenylether), respectively. All complexes were characterized by single‐crystal X‐ray diffraction, spectroscopic analysis (IR, UV‐Vis), elemental analysis, and photoluminescence study. Single‐crystal X‐ray diffraction revealed that complexes 1–3 all adopt discrete cation complex structure with a tetrahedral CuN2P2 coordination geometry with diverse P−Cu−P angles. Their UV‐Vis absorption spectra exhibit a blue‐shift sequence under the enlarging of P−Cu−P angle from 3 to 2 then to 1. The PL emission peak wavelengths of 1–3 also present similar blue‐shift sequence (3→1/2). Their microsecond PL lifetime indicates that their PL behavior belongs to phosphorescence. TD‐DFT calculation and wavefunction analysis illuminate that the S1 and T1 states of 1–3 should all be assigned as (ML+L′L)CT states. Their UV‐Vis absorption and phosphorescence should be attributed to the charge transfer from the P−Cu−P segment to the MePBO ligand. Therefore, as P−Cu−P angle increases (lower HOMO), the energy of S1 and T1 states also increase, following the change of PL color. Additionally, the steric hindrance from substituents of phosphine ligand, as well as extra strong intra‐molecular π−π stacking interactions should effectively inhibit nonradiative decay so that an abnormal PL emission blue‐shift is observed from 1 to 2.
The rapid and accurate detection of ammonia is very important for manufacture and environmental monitoring, which needs to be developed urgently. Herein, a thin film‐based fluorescence sensor is ...fabricated by using a ternary europium (III) complex probe for ammonia. The new complex Eu(TPM)3(2‐PBO) (1) was designed and synthesized by utilizing a trifluoromethyl substituted β‐diketone ligand TPM and a diimine ligand 2‐PBO (TPM = 1,1,1‐trifluoro‐5,5‐dimethyl‐2,4‐hexanedione, 2‐PBO = 2‐(2′‐pyridyl)‐benzoxazole). This complex probe was synthetically characterized by elemental analysis, crystallographic and spectroscopic analysis, and photoluminescence (PL) study. The crystallographic analysis revealed complex 1 as a neutral complex structure with the Eu(III) center in a distorted square antiprism EuO6N2 coordination polyhedron. Based on this complex probe, a thin film fluorescence sensor with highly sensitive and selective response to ammonia was developed by polymethyl methacrylate (PMMA): complex composite and cellulose paper support. When the paper‐based sensor was exposed to ammonia, its PL emission showed a sensing behavior of rapid quenching. Surprisingly, this new method can achieve excellent limit of detection as low as 2.740 × 10−6 ppm.
In this paper, the results of a bibliometric and visual analysis of geo-ontology research articles collected from the Web of Science (WOS) database between 1999 and 2014 are presented. The numbers of ...national institutions and published papers are visualized and a global research heat map is drawn, illustrating an overview of global geo-ontology research. In addition, we present a chord diagram of countries and perform a visual cluster analysis of a knowledge co-citation network of references, disclosing potential academic communities and identifying key points, main research areas, and future research trends. The International Journal of Geographical Information Science, Progress in Human Geography, and Computers & Geosciences are the most active journals. The USA makes the largest contributions to geo-ontology research by virtue of its highest numbers of independent and collaborative papers, and its dominance was also confirmed in the country chord diagram. The majority of institutions are in the USA, Western Europe, and Eastern Asia. Wuhan University, University of Munster, and the Chinese Academy of Sciences are notable geo-ontology institutions. Keywords such as “Semantic Web,” “GIS,” and “space” have attracted a great deal of attention. “Semantic granularity in ontology-driven geographic information systems, “Ontologies in support of activities in geographical space” and “A translation approach to portable ontology specifications” have the highest cited centrality. Geographical space, computer-human interaction, and ontology cognition are the three main research areas of geo-ontology. The semantic mismatch between the producers and users of ontology data as well as error propagation in interdisciplinary and cross-linguistic data reuse needs to be solved. In addition, the development of geo-ontology modeling primitives based on OWL (Web Ontology Language）and finding methods to automatically rework data in Semantic Web are needed. Furthermore, the topological relations between geographical entities still require further study.
•Geo-ontology is quantitatively analyzed using bibliometrics.•The national and institutional features of geo-ontology research are analyzed.•References with the highest centrality are analyzed and clustered.•The relationships of co-citation of references are revealed.•The current research focuses of geo-ontology are revealed.
Four new heteroleptic Cu(NN)P2+‐type cuprous complexes—1‐TPP, 2‐POP, 3‐Xantphos, and 4‐DPPF—were designed and synthesized using a diimine ligand 2‐(2′‐pyridyl)benzoxazole (2‐PBO) and different ...phosphine ligands (TPP, triphenylphosphine; POP, bis2‐(diphenylphosphino)phenylether; Xantphos, 4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene; DPPF, 1,1′‐bis(diphenylphosphino)‐ferrocene). All complexes were characterized using single‐crystal X‐ray diffraction, spectroscopic analysis (infrared, UV–Vis.), elemental analysis, and photoluminescence (PL). Single‐crystal X‐ray diffraction revealed complexes 1–4 as isolated cation complex structures with a tetrahedral CuN2P2 coordination geometry and diverse P–Cu–P angles. Their UV–Vis. absorption spectra exhibited a blue‐shift sequence in wavelength with an enlarged P–Cu–P angle from 4 to 2 then to 3 and then to 1. The PL emission peaks of 1–3 also exhibited a similar blue‐shift sequence (2 → 3 → 1). Their PL lifetime in microseconds (~7.5, 5.1, and 4.7 μs for 1, 2, and 3, respectively) indicated that their PL behavior represents phosphorescence. Time‐dependent density functional theory (TD‐DFT) calculation and wavefunction analysis revealed that S1 and T1 states of 1–3 should be assigned as metal–ligand and ligand–ligand charge‐transfer (ML + L'L)CT states. Their UV–Vis. absorption and phosphorescence should be attributed to the charge transfer from the P–Cu–P segment to the 2‐PBO ligand. Therefore, as the P–Cu–P angle increased (lower HOMO), the energy of S1 and T1 states also increased, following the change of PL color.
Four new Cu(NN)P2+type complexes are constructed by 2‐PBOand different phosphine ligands, TPP(1), POP(2), Xantphos(3), and DPPF(4). Obvious wavelength shifts (color change) are observed in their UV and PL spectra of 1–3. TD‐DFT calculation and wavefunction analysis visually reveal their absorption and phosphorescence transitions should be assigned as 1(ML + LL)CT (S1) and 3(ML + LL)CT (T1) excited states, meanwhile, the wavelength shifts are successfully clarified using a positive correlation of P–Cu–P angle and excited‐state (S1/T1) state energy.
PDF
