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Dempsey Combs opublikował 1 rok, 3 miesiące temu
These results suggest that a cocktail of IL-18 and IL-22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti-PD-1 immunotherapy. The mechanism of liver metastases-induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen specific and associated with the coordinated activation of regulatory T cells (Tregs) and modulation of intratumoral CD11b+ monocytes. The dysfunctional immune state could not be reversed by anti-PD-1 monotherapy unless Treg cells were depleted (anti-CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding Treg and CD11b+ monocyte targeting agents in combination with anti-PD-1 to treat patients with cancer with liver metastasis.Quantum dots have innate advantages as the key component of optoelectronic devices. For white light-emitting diodes (WLEDs), the modulation of the spectrum and color of the device often involves various quantum dots of different emission wavelengths. Here, we fabricate a series of carbon quantum dots (CQDs) through a scalable acid reagent engineering strategy. The growing electron-withdrawing groups on the surface of CQDs that originated from acid reagents boost their photoluminescence wavelength red shift and raise their particle sizes, elucidating the quantum size effect. These CQDs emit bright and remarkably stable full-color fluorescence ranging from blue to red light and even white light. Full-color emissive polymer films and all types of high-color rendering index WLEDs are synthesized by mixing multiple kinds of CQDs in appropriate ratios. The universal electron-donating/withdrawing group engineering approach for synthesizing tunable emissive CQDs will facilitate the progress of carbon-based luminescent materials for manufacturing forward-looking films and devices.Students who speak English as a second language (ESL) are underserved and underrepresented in postsecondary science, technology, engineering, and math (STEM) fields. To date, most existing research with ESL students in higher education is qualitative. Drawing from this important body of work, we investigate the impact of a social-belonging intervention on anticipated changes in belonging, STEM GPA, and proportion of STEM credits obtained in students’ first semester and first year of college. Using data from more than 12,000 STEM-interested students at 19 universities, results revealed that the intervention increased ESL students’ anticipated sense of belonging and three of the four academic outcomes. Moreover, anticipated changes in belonging mediated the intervention’s effects on these academic outcomes. Robustness checks revealed that ESL effects persisted even when controlling for other identities correlated with ESL status. Overall, results suggest that anticipated belonging is an understudied barrier to creating a multilingual and diverse STEM workforce.Cancer vaccines have been actively pursued to bolster antitumor immunity. Here, we designed nanoscale metal-organic frameworks (nMOFs) as locally activable immunotherapeutics to release danger-associated molecular patterns (DAMPs) and tumor antigens and deliver pathogen-associated molecular patterns (PAMPs) for in situ personalized cancer vaccination. When activated by x-rays, nMOFs effectively generate reactive oxygen species to release DAMPs and tumor antigens while delivering CpG oligodeoxynucleotides as PAMPs to facilitate the maturation of antigen-presenting cells. Together, DAMPs, tumor antigens, and PAMPs expand cytotoxic T cells in tumor-draining lymph nodes to reinvigorate the adaptive immune system for local tumor regression. When treated in combination with an immune checkpoint inhibitor, the local therapeutic effects of nMOF-based vaccines were extended to distant tumors via attenuating T cell exhaustion. Our work demonstrates the potential of nMOFs as x-ray-activable in situ cancer vaccines to awaken the host’s innate and adaptive immune systems for systemic antitumor immunity.Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. The matrix was designed to mimic physical and biomolecular features of tumors present in patients. We included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells. The multicellular constructs supported the formation of tumor spheroids with extensive F-actin networks surrounding the spheroids, enabling cell-cell communication, and comparative cell-matrix interactions and encapsulation response to those observed in Matrigel. We conducted a proof-of-concept study with clinically used chemotherapeutics to validate the functionality of the multicellular constructs. Our study demonstrates that peptide-protein coassembling matrices serve as a defined model of the multicellular tumor microenvironment of primary ovarian tumors.The crusts of the Moon, Mercury, and many meteorite parent bodies are magnetized. Although the magnetizing field is commonly attributed to that of an ancient core dynamo, a longstanding hypothesized alternative is amplification of the interplanetary magnetic field and induced crustal field by plasmas generated by meteoroid impacts. Here, we use magnetohydrodynamic and impact simulations and analytic relationships to demonstrate that although impact plasmas can transiently enhance the field inside the Moon, the resulting fields are at least three orders of magnitude too weak to explain lunar crustal magnetic anomalies. This leaves a core dynamo as the only plausible source of most magnetization on the Moon.Observations of coral reef losses to climate change far exceed our understanding of historical degradation before anthropogenic warming. This is a critical gap to fill as conservation efforts simultaneously work to reverse climate change while restoring coral reef diversity and function. Here, we focused on southern China’s Greater Bay Area, where coral communities persist despite centuries of coral mining, fishing, dredging, development, and pollution. We compared subfossil assemblages with modern-day communities and revealed a 40% decrease in generic diversity, concomitant to a shift from competitive to stress-tolerant species dominance since the mid-Holocene. Regions with characteristically poor water quality-high chl-a, dissolved inorganic nitrogen, and turbidity-had lower contemporary diversity and the greatest community composition shift observed in the past, driven by the near extirpation of Acropora These observations highlight the urgent need to mitigate local stressors from development in concert with curbing greenhouse gas emissions.Wave fields with orbital angular momentum (OAM) have been widely investigated in metasurfaces. By engineering acoustic metasurfaces with phase gradient elements, phase twisting is commonly used to obtain acoustic OAM. However, it has limited ability to manipulate sound vortices, and a more powerful mechanism for sound vortex manipulation is strongly desired. Here, we propose the diffraction mechanism to manipulate sound vortices in a cylindrical waveguide with phase gradient metagratings (PGMs). A sound vortex diffraction law is theoretically revealed based on the generalized conservation principle of topological charge. This diffraction law can explain and predict the complicated diffraction phenomena of sound vortices, as confirmed by numerical simulations. To exemplify our findings, we designed and experimentally verified a PGM based on Helmholtz resonators that support asymmetric transmission of sound vortices. Our work provides previously unidentified opportunities for manipulating sound vortices, which can advance more versatile design for OAM-based devices.Spin electronic devices based on crystalline oxide layers with nanoscale thicknesses involve complex structural and magnetic phenomena, including magnetic domains and the coupling of the magnetism to elastic and plastic crystallographic distortion. The magnetism of buried nanoscale layers has a substantial impact on spincaloritronic devices incorporating garnets and other oxides exhibiting the spin Seebeck effect (SSE). Synchrotron hard x-ray nanobeam diffraction techniques combine structural, elemental, and magnetic sensitivity and allow the magnetic domain configuration and structural distortion to be probed in buried layers simultaneously. Resonant scattering at the Gd L2 edge of Gd3Fe5O12 layers yields magnetic contrast with both linear and circular incident x-ray polarization. Domain patterns facet to form low-energy domain wall orientations but also are coupled to elastic features linked to epitaxial growth. Nanobeam magnetic diffraction images reveal diverse magnetic microstructure within emerging SSE materials and a strong coupling of the magnetism to crystallographic distortion.Do sexual and gender minorities (SGMs) in the United States encounter disproportionate rates of victimization as compared with their cisgender, heterosexual counterparts? Answering this question has proved elusive because nationally representative victimization data have not included victims’ sexual orientation or gender identity. The National Crime Victimization Survey, the nation’s primary source of representative information on criminal victimization, began documenting sexual orientation and gender identity in 2016 and released data publicly for the first time in 2019. We find SGMs disproportionately are victims across a variety of crimes. The rate of violent victimization for SGMs is 71.1 victimizations per 1000 people compared with 19.2 victimizations per 1000 people for those who are not SGMs. SGMs are 2.7 times more likely to be a victim of violent crime than non-SGMs. These findings raise the importance of further considering sexual orientation and gender identity in victimization and interventions.Proteomic profiling of circulating small extracellular vesicles (sEVs) represents a promising, noninvasive approach for early detection and therapeutic monitoring of breast cancer (BC). We describe a relatively low-cost, fast, and reliable method to isolate sEVs from plasma of BC patients and analyze their protein content by semiquantitative proteomics. sEV-enriched fractions were isolated from plasma of healthy controls and BC patients at different disease stages before and after surgery. Proteomic analysis of sEV-enriched fractions using reverse phase protein array revealed a signature of seven proteins that differentiated BC patients from healthy individuals, of which FAK and fibronectin displayed high diagnostic accuracy. The size of sEVs was significantly reduced in advanced disease stage, concomitant with a stage-specific protein signature. Furthermore, we observed protein-based distinct clusters of healthy controls, chemotherapy-treated and untreated postsurgery samples, as well as a predictor of high risk of cancer relapse, suggesting that the applied methods warrant development for advanced diagnostics.


