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This study examines the modifications of air-sea coupling processes by dust-radiation-cloud interactions over the North Atlantic Ocean using a high-resolution coupled atmosphere-wave-ocean-dust (AWOD) regional model. The dust-induced mechanisms that are responsible for changes of sea surface temperature (SST) and latent and sensible heat fluxes (LHF/SHF) are also examined. Two 3-month numerical experiments are conducted, and they differ only in the activation and deactivation of dust-radiation-cloud interactions. Model results show that the dust significantly reduces surface downward radiation fluxes (SDRF) over the ocean with the maximum change of 20-30 W m-2. Over the dust plume region, the dust effect creates a low-pressure anomaly and a cyclonic circulation anomaly, which drives a positive wind stress curl anomaly, thereby reducing sea surface height and mixed layer depth. However, the SST change by dust, ranging from -0.5 to 0.5 K, has a great spatial variation which differs from the dust plume shape. Dust cools SST around the West African coast, except under the maximum dust plume ridge, and extends westward asymmetrically along the northern and southern edges of the dust plume. Dust unexpectedly warms SST over a large area of the western tropical North Atlantic and north of the dust plume. These SST changes are controlled by different mechanisms. Unlike the SST change pattern, the LHF and SHF changes are mostly reduced underneath the dust plume region, though they are different in detail due to different dominant factors, and increased south of the dust plume over the tropic.

This study evaluates the impact of assimilating moderate resolution imaging spectroradiometer (MODIS) aerosol optical depth (AOD) data using different data assimilation (DA) methods on dust analyses and forecasts over North Africa and tropical North Atlantic. To do so, seven experiments are conducted using the Weather Research and Forecasting dust model and the Gridpoint Statistical Interpolation analysis system. Six of these experiments differ in whether or not AOD observations are assimilated and the DA method used, the latter of which includes the three-dimensional variational (3D-Var), ensemble square root filter (EnSRF), and hybrid methods. The seventh experiment, which allows us to assess the impact of assimilating deep blue AOD data, assimilates only dark target AOD data using the hybrid method. The assimilation of MODIS AOD data clearly improves AOD analyses and forecasts up to 48 hr in length. Results also show that assimilating deep blue data has a primarily positive effect on AOD analyses and forecasts over and downstream of the major North African source regions. Without assimilating deep blue data (assimilating dark target only), AOD assimilation only improves AOD forecasts for up to 30 hr. Of the three DA methods examined, the hybrid and EnSRF methods produce better AOD analyses and forecasts than the 3D-Var method does. Despite the clear benefit of AOD assimilation for AOD analyses and forecasts, the lack of information regarding the vertical distribution of aerosols in AOD data means that AOD assimilation has very little positive effect on analyzed or forecasted vertical profiles of backscatter.

NK2 Homeobox 1 (NKX2‐1) is a well‐characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2‐1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2‐1 is observed in high‐grade LUAD. Meanwhile, single‐cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell‐cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2‐1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT‐PCR. ATAC‐seq revealed the restrictive regulation of NKX2‐1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2‐1 modulates the infiltration of tumor‐promoting neutrophils by inhibiting CXCLs/CXCR2‐dependent mechanisms. Hence, targeting CXCR2 in NKX2‐1‐low tumors is a potential antitumor therapy that may improve LUAD patient outcomes. [ABSTRACT FROM AUTHOR]

Eye fundus diseases, such as retinal degenerative diseases, which lead to blindness in ≈12% of individuals aged >65 years, cause permanent damage to retinal cells. The antioxidant quercetin (QC) is promising for the effective treatment of eye fundus diseases; however, its poor solubility and low retention rate often limit its clinical application. Herein, an in situ ophthalmic tethered gold yarnball (GY) that doubles as an ocular retention agent and QC reservoir to overcome low fundus drug retention is developed. After intravitreal injection, QC@GYs enhance retinal cell leakage and internal limiting membrane permeability, facilitating the partial penetration of QC@GYs into the intraretinal tissue. The combination of retina‐tethered QC@GY and first‐level sustained release reduces macular degeneration in vivo by effectively regulating oxidative stress. Furthermore, the sustained release of QC preserves the viability of retinal pigment epithelium cells, reduces apoptosis, and suppresses drusen formation. This preservation of retinal morphology and function maximizes the therapeutic impact while minimizing the need for frequent intraocular administration. Overall, the ophthalmic tethered GY platform is a versatile tool for retinal drug delivery for the treatment of eye fundus diseases. [ABSTRACT FROM AUTHOR]

Clathrin heavy chain 22 (CHC22) is an isoform of the well-characterized CHC17 clathrin heavy chain, a coat component of vesicles that mediate endocytosis and organelle biogenesis. CHC22 has a distinct role from CHC17 in trafficking glucose transporter 4 (GLUT4) in skeletal muscle and fat, though its transfection into HEK293 cells suggests functional redundancy. Here, we show that CHC22 is eightfold less abundant than CHC17 in muscle, other cell types have variably lower amounts of CHC22, and endogenous CHC22 and CHC17 function independently in nonmuscle and muscle cells. CHC22 was required for retrograde trafficking of certain cargo molecules from endosomes to the trans-Golgi network (TGN), defining a novel endosomal-sorting step distinguishable from that mediated by CHC17 and retromer. In muscle cells, depletion of syntaxin 10 as well as CHC22 affected GLUT4 targeting, establishing retrograde endosome-TGN transport as critical for GLUT4 trafficking. Like CHC22, syntaxin 10 is not expressed in mice but is present in humans and other vertebrates, implicating two species-restricted endosomal traffic proteins in GLUT4 transport.

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.