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Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage. [ABSTRACT FROM AUTHOR]

Eosinophils are important immune effector cells that affect T cell‐mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the outcome of cancer immunotherapies. We herein report an eosinophil‐activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T‐cell immunity for activated cancer photo‐immunotherapy. SPNe comprises an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2‐cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe generates 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe‐mediated photo‐immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Precise control of dispersion output holds paramount significance across domains such as optical fiber communication, time stretching, and spectral interferometric ranging. In comparison to other dispersion elements, like prisms, gratings are widely applied in the field of dispersion control due to their advantages of broad spectral range, tunability, and high resolution. Moreover, linear dispersion is the most desired characteristic by designers in most cases. Here, we develop a dispersion model for grating groups to determine the optimal structural parameters for achieving linear dispersion in high-order grating arrays. Based on our model, we provide corresponding parameter selection methods that allow for quantitative design of the size and slope of output dispersion by adjusting input parameters such as angle, distance, and parallelism. Additionally, we experimentally establish a dispersion interferometry structure based on the grating ensemble that validates our proposed approach's capability for linear dispersion output (linearity better than 0.9998). We believe that our approach is universally significant and contributes to enhancing the performance of dispersion interferometric measurement systems, chirp amplification systems, and other related systems. [ABSTRACT FROM AUTHOR]

The efficacy of combination immunotherapy has been limited by tumor specificity and immune‐related adverse events (irAEs). Herein, we report the development of polymeric STING pro‐agonists (PSPA), whose sono‐immunotherapeutic efficacy is activated by sono‐irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA‐2) via the GSH‐activatable linkers. Under sono‐irradiation, PSPA serves as a sonosensitizer to generate 1O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA‐2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off‐target side effects. The activation of the STING pathway elevates the interferon‐β level and synergizes with SDT to enhance the anti‐tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono‐immunotherapy. [ABSTRACT FROM AUTHOR]

InGaN red light emitting diode (LED) is one of the crucial bottlenecks that must be broken through to realize high‐resolution full‐color mini/micro‐LED displays. The efficiency of InGaN LEDs drops rapidly as the emission spectra go from blue/green to red range due to the poor quality of high‐indium‐content InGaN materials. Here, high‐performance InGaN red LEDs on sapphire grown by metal–organic chemical vapor deposition through strain modulation are reported. A composite buffer layer is proposed to increase the surface lattice constant of GaN and hence successfully enhances the indium incorporation efficiency of the following InGaN active layers. Consequently, a high‐efficiency InGaN red mini‐LED chip (mesa area: 100 × 200 µm2) with a peak wavelength of 629 nm and an external quantum efficiency of 7.4% is realized. Finally, a full‐color nitride mini‐LED display panel with 74.1% coverage of Rec.2020 color gamut by using the InGaN red mini‐LED chips is fabricated. The study signifies the great potentials of full‐nitrides high‐resolution full‐color mini/micro‐LED displays. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer‐based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer‐specific inhibition of collagen‐crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo‐immunotherapy. SPNcb is self‐assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β‐aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)‐cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor‐overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis. [ABSTRACT FROM AUTHOR]