Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through ...expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.
Abstract
Strong many-body interaction in two-dimensional transitional metal dichalcogenides provides a unique platform to study the interplay between different quasiparticles, such as prominent ...phonon replica emission and modified valley-selection rules. A large out-of-plane magnetic field is expected to modify the exciton-phonon interactions by quantizing excitons into discrete Landau levels, which is largely unexplored. Here, we observe the Landau levels originating from phonon-exciton complexes and directly probe exciton-phonon interaction under a quantizing magnetic field. Phonon-exciton interaction lifts the inter-Landau-level transition selection rules for dark trions, manifested by a distinctively different Landau fan pattern compared to bright trions. This allows us to experimentally extract the effective mass of both holes and electrons. The onset of Landau quantization coincides with a significant increase of the valley-Zeeman shift, suggesting strong many-body effects on the phonon-exciton interaction. Our work demonstrates monolayer WSe
2
as an intriguing playground to study phonon-exciton interactions and their interplay with charge, spin, and valley.
Objective
This study aimed to explore the characteristics of the top 100 influential manuscripts on obstructive sleep apnea (OSA).
Methods
All manuscripts in English were searched from the Thomson ...Reuters Web of Science database by using OSA-related terms and ranked based on citation frequency. The top 100 influential manuscripts were selected and further analyzed by author, subject, journal, year of publication, country of origin, and institution.
Results
A total of 42,878 manuscripts were searched from the Web of Science. The top 100 influential manuscripts were published from 2005 to 2017, with a total citation frequency of 38,463 and a median citation frequency of 303 (range: from 210 to 2, 707). The
American Journal of Respiratory and Critical Care Medicine
published the largest number of manuscripts from the top 100 (
n
= 18; 5340 citations), followed by
Sleep
(
n
= 11; 3516 citations) and
Chest
(
n
= 7; 1784 citations). The most cited manuscript (Marin, J.M et al.,
Lancet
2005; 2707 citations) mainly analyzed long-term cardiovascular outcomes in men with OSA with/without continuous positive airway pressure. The most prevalent subject was associated diseases (
n
= 41), followed by treatments (
n
= 40). Most of the manuscripts were original articles (
n
= 63) based on observational clinical studies and published from American institutions (
n
= 60).
Conclusions
Our study identified the top 100 influential manuscripts on OSA and provides insights into the characteristics of the most highly cited manuscripts to improve our understanding and management of OSA.
Abstract
Moiré coupling in transition metal dichalcogenides (TMDCs) superlattices introduces flat minibands that enable strong electronic correlation and fascinating correlated states, and it also ...modifies the strong Coulomb-interaction-driven excitons and gives rise to moiré excitons. Here, we introduce the layer degree of freedom to the WSe
2
/WS
2
moiré superlattice by changing WSe
2
from monolayer to bilayer and trilayer. We observe systematic changes of optical spectra of the moiré excitons, which directly confirm the highly interfacial nature of moiré coupling at the WSe
2
/WS
2
interface. In addition, the energy resonances of moiré excitons are strongly modified, with their separation significantly increased in multilayer WSe
2
/monolayer WS
2
moiré superlattice. The additional WSe
2
layers also modulate the strong electronic correlation strength, evidenced by the reduced Mott transition temperature with added WSe
2
layer(s). The layer dependence of both moiré excitons and correlated electronic states can be well described by our theoretical model. Our study presents a new method to tune the strong electronic correlation and moiré exciton bands in the TMDCs moiré superlattices, ushering in an exciting platform to engineer quantum phenomena stemming from strong correlation and Coulomb interaction.
Transition metal dichalcogenide (TMDC) moiré superlattices, owing to the moiré flatbands and strong correlation, can host periodic electron crystals and fascinating correlated physics. The TMDC ...heterojunctions in the type-II alignment also enable long-lived interlayer excitons that are promising for correlated bosonic states, while the interaction is dictated by the asymmetry of the heterojunction. Here we demonstrate a new excitonic state, quadrupolar exciton, in a symmetric WSe
-WS
-WSe
trilayer moiré superlattice. The quadrupolar excitons exhibit a quadratic dependence on the electric field, distinctively different from the linear Stark shift of the dipolar excitons in heterobilayers. This quadrupolar exciton stems from the hybridization of WSe
valence moiré flatbands. The same mechanism also gives rise to an interlayer Mott insulator state, in which the two WSe
layers share one hole laterally confined in one moiré unit cell. In contrast, the hole occupation probability in each layer can be continuously tuned via an out-of-plane electric field, reaching 100% in the top or bottom WSe
under a large electric field, accompanying the transition from quadrupolar excitons to dipolar excitons. Our work demonstrates a trilayer moiré system as a new exciting playground for realizing novel correlated states and engineering quantum phase transitions.
CsPbBr3 nanoplates (NPs) have shown great potential in diverse optoelectronic applications. Despite the wonderful luminescence properties, the inherent instability of these NPs hinders their use in ...practical situations. Herein, a facile water‐assisted strategy is reported to synthesize highly stable blue emission CsPbBr3 NPs encapsulated in PbBr(OH). The introduction of water directly into the reaction mixture is pivotal, as it triggers the transformation of bulk CsPbBr3 nanocubes into 2‐D CsPbBr3 NPs within the PbBr(OH) matrix, resulting in the formation of CsPbBr3@PbBr(OH) microbricks. Remarkably, the water content in the reaction mixture allows the control of the number of perovskite layers in the NPs, thus enabling the emission color to be tuned from deep blue to green. The unconventional approach presented herein not only offers a cost‐effective pathway to synthesize blue‐emitting perovskites which are highly stable in a wide variety of polar and non‐polar solvents, but also holds immense potential for propelling the advancement of high‐performance LEDs and other optoelectronic devices. The findings underscore the significance of water in dictating the growth dynamics and emission characteristics of perovskite NPs, paving the way for their practical application.
Water slowly dissolves the CsPbBr3 nanocrystals and creates a Cs‐deficit environment for the subsequent growth of blue‐emitting CsPbBr3 NPs, which are eventually embedded inside a large PbBr(OH) matrix. This 3‐step process effectively favors the formation of NPs in which the number of layers and the emission wavelength can be manipulated with the water content.
Permeation grouting is widely used in grouting engineering because of its low grouting pressure and minor disturbance to the stratum. However, influenced by the complex properties of sand layer and ...slurry, an accurate prediction of the groutability of the sand layer remains to be a hard work. In this paper, the permeability of sand layer is studied based on a self-designed permeation grouting test device, which considers the different sand particle size, relative density of sand layer, slurry water-cement ratio, and clay content. The influencing factors of sand layer groutability are analyzed, and the different parameters that affect the grouting of sand layer are evaluated, thus proposing a new approach to predict the groutability of sand layer. Results show that the sand particle size and slurry water-cement ratio are positively related to the groutability of sand layer, and the relative density and clay content of sand layer are negatively correlated with the groutability of sand layer. The proposed alternative empirical formula to estimate the groutability of sand layer will help predict the groutability of sand layer with a higher degree of accuracy, which can provide a certain reference for engineering.
Oxidative potential (OP) reflects integratedtoxicity of PM2.5. Therefore, OP of PM2.5 samples collected from traditional central and suburban areas (Gulou and Xianlin) in Nanjing, a megacity of ...China, from Jan. 2020 to Jun. 2021 was analyzed by using two abiotic assays, DTT and AA assays (OPDTT and OPAA). Values of OPDTTv and OPAAv were 0.82 ~ 3.82 and 0.15 ~ 2.22 nmol/min/m3, respectively. The OP values of PM2.5 samples collected from the Xianlin were higher than those from the Gulou by using both the DTT assay and the AA assay in this study, suggesting the seasonal and spatial variation. Moreover, OP values analyzed by using DTT assay were higher than those by using AA assay. Based on Positive Matrix Factorization (PMF), the major pollution source of the OP of PM2.5 in Nanjing was combustion source. This study may be helpful for evaluating adverse health risks of PM2.5 in a megacity.
DNAX-activating protein of 12 kDa (DAP12) is a signaling adapter protein expressed in cells that participate in innate immune responses. By pairing with different triggering receptors expressed on ...myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular responses. In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator. TREM2 has also been shown to stimulate the phagocytosis of apoptotic neurons and define the barrier function in microglia. Notably, loss-of-function mutations of either
or
result in a disorder known as Nasu-Hakola disease (NHD); and mutations of these genes have been associated with the risk for Alzheimer's disease (AD), suggesting that TREM2 and DAP12 may regulate common signaling pathways in the disease pathogenesis. In this study, we demonstrated an anti-inflammatory role of DAP12 in murine microglia that depends on the presence of TREM2. We also uncovered the JNK signaling pathway as the underlying molecular mechanism by which the TREM2/DAP12 complex suppresses the hyperactivation of microglia upon LPS stimulation. Interestingly, LPS down-regulates the expression of
via the activation of JNK and NF-κB signaling pathways, resulting in a vicious cycle that synergistically promotes the inflammatory responses. Our study provides insights into mechanism-based therapy for neuroinflammatory disorders.
Abstract
Background
Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress ...affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females.
Method/Results
Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors.
Conclusions
Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.
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