Abciximab, a derivative of the murine mAb 7E3, protects against ischemic complications of percutaneous coronary interventions by inhibiting ligand binding to the ␣IIb␤3 receptor. In this study we identified regions on integrin ␤3 that control 7E3 binding. Murine͞ human amino acid substitutions were created in two regions of the ␤A domain that previous studies found to influence 7E3 binding: the C177-C184 loop and K125-N133. The T182N substitution and a K125Q mutation reduced 7E3 binding to human ␤3 in complex with ␣IIb. The introduction of both the human C177-C184 region and human W129 into murine ␤3 was necessary and sufficient to permit 7E3 binding to the human ␣IIb͞murine ␤3 complex. Although we cannot exclude allosteric effects, we propose that 7E3 binds between C177-C184 and W129, which are within 15 Å of each other in the crystal structure and close to the ␤3 metal ion-dependent adhesion site. We previously demonstrated that 7E3 binds more rapidly to activated than unactivated platelets. Because it has been proposed that ␣IIb␤3 changes from a bent to an extended conformation upon activation, we hypothesized that 7E3 binds less well to the bent than the extended conformation. In support of this hypothesis we found that 7E3 bound less well to an ␣IIb␤3 construct locked in a bent conformation, and unlocking the conformation restored 7E3 binding. Thus, our data are consistent with ␣IIb␤3 existing in variably bent conformations in equilibrium with each other on unactivated platelets, and activation resulting in ␣IIb␤3 adopting a more extended conformation.T he integrin ␣IIb␤3 and ␣V␤3 receptors are important in a number of physiologic and pathologic phenomena, including hemostasis, thrombosis, tumor angiogenesis, and bone resorption (1, 2). The murine mAb 7E3 (3) blocks ligand binding to both ␣IIb␤3 and ␣V␤3 receptors (4, 5). Abciximab is a mouse͞ human chimeric Fab fragment of the mAb 7E3 that inhibits ␣IIb␤3-mediated platelet aggregation and is approved for human use to prevent the ischemic complications associated with percutaneous coronary interventions (6).Previous studies of 7E3 binding to cells expressing recombinant ␣IIb␤3 receptors demonstrated that: (i) swapping select murine for human ␣IIb sequences does not decrease 7E3 binding (7), (ii) removing the specificity determining loop (SDL) (K156-G189 sequence) from ␤3 results in loss of 7E3 binding (8), (iii) swapping the murine for human C177-C184 sequence within the SDL region in ␤3 results in loss of 7E3 binding (7), and (iv) swapping the murine S129-T133 sequence for the human W129-N133 sequence results in partial loss of 7E3 binding (7).The above human͞mouse swapping studies identified regions within ␤3 that affect 7E3 binding, but the biochemical and functional properties of these chimeric receptors were not characterized. In addition, the W129-N133 region contains two amino acid differences between human ␤3 (␤3Hu) and mouse ␤3 (␤3M) and the C177-C184 region contains three amino acid differences (Table 1). To define further the regions on ␣IIb␤3 th...

Background: Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. Methods: We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990-2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. Results: Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] − 0.03 to 0.08), but the agestandardized death (EAPC = − 0.34, 95%CI − 0.38 to − 0.3) and DALY rate decreased generally (EAPC = − 0.74, 95%CI − 0.8 to − 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 − 69 years.

Living organisms in nature have amazing control over their color, shape, and morphology in response to environmental stimuli for camouflage, communication, or reproduction. Inspired by the camouflage of the octopus via the elongation or contraction of its pigment cells, oblate cholesteric liquid crystal droplets are dispersed in a polymer matrix, serving as the role of pigment cells and showing structural color due to selective Bragg reflection by their periodic helical structure. The color of 3D‐printed biomimetic systems can be tuned by changing the helical pitch via the chiral dopant concentration or temperature. When the oblate liquid crystal droplets are heated up to isotropic, the opaque and colored biomimetic systems become transparent and colorless. Meanwhile, the isotropic liquid crystal droplets tend to become spherical, causing volume contraction along the film plane and volume dilation in the perpendicular direction. The internal strain combined with the gradient distribution of the oblate isotropic liquid crystal droplets result in corresponding shape transformations. The camouflage of a biomimetic octopus and the blossom of a biomimetic flower, both of which show synergetic color and shape responses, are demonstrated to inspire the design of functional materials and intelligent devices.

Properties of emulsions highly depend on the interdroplet interactions and, thus, engineering interdroplet interactions at molecular scale are essential to achieve desired emulsion systems. Here, attractive Pickering emulsion gels (APEGs) are designed and prepared by bridging neighboring particle‐stabilized droplets via telechelic polymers. In the APEGs, each telechelic molecule with two amino end groups can simultaneously bind to two carboxyl functionalized nanoparticles in two neighboring droplets, forming a bridged network. The APEG systems show typical shear‐thinning behaviors and their viscoelastic properties are tunable by temperature, pH, and molecular weight of the telechelic polymers, making them ideal for direct 3D printing. The APEGs can be photopolymerized to prepare APEG‐templated porous materials and their microstructures can be tailored to optimize their performances, making the APEG systems promising for a wide range of applications.

Key Points Question What are the temporal trends and epidemiological distribution of mesothelioma, and have cases of mesothelioma increased worldwide since 1990? Findings In this cross-sectional study of 21 regions comprising 195 countries and territories, global mesothelioma cases continuously increased, with more than 50% of cases recorded in regions with high sociodemographic index levels; in recent years, incidence and mortality also increased, especially among female individuals, in regions with low sociodemographic index levels. Meaning This study found that incident mesothelioma cases and deaths associated with mesothelioma have continuously increased worldwide, especially in resource-limited regions in which a complete and immediate ban on asbestos use may be warranted.

Concentrating a trace amount of molecules from liquids, solid objects, or the gas phase and delivering them to a localized area are crucial for almost any trace analyte detection device. Analytes within a liquid droplet resting on micro/nanostructured surfaces with liquid-repellent coatings can be concentrated during solvent evaporation. However, these coatings suffer from complex manufacturing procedures, poor versatility, and limited analyte enrichment efficiency. Here, we report on the use of an acoustic levitation platform to losslessly concentrate the analyte molecules dissolved in any volatile liquid, attached to solid objects, or spread in air. Gold nanoparticles can be simultaneously concentrated with the analytes in different phases, realizing sensitive, surface-enhanced Raman scattering detection even at attomolar (10−18 mol/L) concentration levels. The acoustic levitation platform-enabled, lossless analyte enrichment can significantly increase the analytical performance of many conventional microsensing techniques.

Glanzmann thrombasthenia (GT) is an inherited disorder where an absence of platelet aggregation is associated with quantitative or qualitative abnormalities of the alphaIIbbeta3 integrin. In rare patients, amino acid substitutions have provided information on the functional significance of specific domains within alphaIIb or beta3. We now report an elderly male GT patient (R.M.) from the south west of France whose platelets possess a small residual expression of alphaIIbbeta3. Furthermore, the integrin failed to undergo the necessary conformational changes following platelet activation to permit the binding of fibrinogen or activation-dependent monoclonal antibodies despite the presence of an RGD-binding site. Screening of the alphaIIb and beta3 genes by PCR-SSCP revealed a heterozygous mutation at position 685 in exon 5 of the beta3 gene leading to a 196Leu to Pro substitution. 196Leu is a highly conserved amino acid of beta3. The other beta3 allele appeared to be silent. This mutation, inherited from his mother and present in other family members with intermediate levels of alphaIIbbeta3, was close to the MIDAS-like domain of beta3, a fact that appears to explain its effect on alphaIIbbeta3 activation and fibrinogen binding.

Objective Cell‐free circular RNAs (circRNAs) are stable and abundantly exist in body fluids. In this study, we aimed to investigate plasma cell‐free circRNAs as a novel class of biomarkers for the diagnosis of breast cancer (BC). Methods Differentially expressed circRNAs from 6 normal and 6 BC plasma samples were detected by microarray. Hsa_circ_0008673 was then screened and validated in the plasma of 102 normal and 378 BC samples. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The correlations between hsa_circ_0008673 expression and demographic characteristics, tumor features, and prognosis were analyzed. The effects of hsa_circ_0008673 on BC cell proliferation and metastasis were also measured. Results Of the top ten up‐regulated (hsa_circ_0008673, hsa_circ_0008500, hsa_circ_0005260, hsa_circ_0003423, hsa_circ_0119881, hsa_circ_0000987, hsa_circ_0007386, hsa_circ_0000091, hsa_circ_0016601, and hsa_circ_0008549) and top ten down‐regulated (hsa_circ_0000826, hsa_circ_0072697, hsa_circ_0004587, hsa_circ_0000471, hsa_circ_0007786, hsa_circ_0001417, hsa_circ_0005982, hsa_circ_0001566, hsa_circ_0003823, and hsa_circ_0003823) circRNAs from microarray, hsa_circ_0008673 was the most significantly up‐regulated circRNA in BC, and represented a good diagnostic value. Hsa_circ_0008673 was remarkably down‐regulated after breast mastectomy. Hsa_circ_0008673 expression was associated with larger tumor size, distant metastasis, positive estrogen receptor (ER) status, and positive progesterone receptor (PR) status. Additionally, hsa_circ_0008673 could serve as a prognostic predicator of overall survival (OS) and disease‐specific survival (DSS). Cell assays proved that hsa_circ_0008673 knockdown contributed to inhibition of tumor cell proliferation and migration. Conclusion Plasma cell‐free hsa_circ_0008673 was up‐regulated in BC, which was associated with poorer prognosis and promoted tumor proliferation and metastasis. Hsa_circ_0008673 is a promising biomarker for tumor diagnosis and prognostic assessment of BC patients.