All inorganic CsPbBr3 perovskite quantum dots (QDs) are potential emitters for electroluminescent displays. We have developed a facile hot‐injection method to partially replace the toxic Pb2+ with ...highly stable Sn4+. Meanwhile, the absolute photoluminescence quantum yield of CsPb1−xSnxBr3 increased from 45 % to 83 % with SnIV substitution. The transient absorption (TA) exciton dynamics in undoped CsPbBr3 and CsPb0.67Sn0.33Br3 QDs at various excitation fluences were determined by femtosecond transient absorption, time‐resolved photoluminescence, and single‐dot spectroscopy, providing clear evidence for the suppression of trion generation by Sn doping. These highly luminescent CsPb0.67Sn0.33Br3 QDs emit at 517 nm. A device based on these QDs exhibited a luminance of 12 500 cd m−2, a current efficiency of 11.63 cd A−1, an external quantum efficiency of 4.13 %, a power efficiency of 6.76 lm w−1, and a low turn‐on voltage of 3.6 V, which are the best values among reported tin‐based perovskite quantum‐dot LEDs.
Suppressed trion formation: CsPb1−xSnxBr3 quantum dots (QDs) were synthesized by a hot‐injection approach. As trion formation is suppressed by the SnIV substitution, light‐emitting diodes (LEDs) based on these highly luminescent QDs performed very well, with the highest current efficiencies and external quantum efficiencies ever reported for such Sn‐based systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A 3-year-old spayed female domestic short-haired cat presented with a head turning to the left, circling to the right, seizures, and opisthotonos for approximately one month. Neurological examination ...revealed a deficit in the postural reaction of the left limbs and visual abnormalities. Forensic computed tomography revealed a hyperattenuating round mass of 1.3 cm diameter with a hypoattenuating center in the right hemisphere. Histopathology showed multifocal granuloma lesions with the major mass mostly affecting the right basal ganglia. Cryptococcus neoformans variety grubii molecular type VNI/ST31 was isolated from the cryptococcal granulomas. This report highlights the epidemiological distribution and differential diagnosis of a feline central nervous system cryptococcosis caused by C. neoformans that occurred in an Asian country.
SCOPE: We investigated whether rutin, a flavonoid isolated from Toona sinensis Roem, has the ability to enhance insulin‐dependent receptor kinase (IRK) activity and glucose transporter 4 (GLUT4) ...translocation in differentiated myotubes. We also tested the effects of rutin treatment in insulin‐resistant mice using an oral glucose tolerance test (OGTT). METHODS AND RESULTS: Rutin potentiated insulin receptor kinase (IRK) phosphorylation when IRK autophosphorylation was triggered by insulin in differentiated myotubes. Co‐treatment of cells with rutin and insulin attenuated S961‐mediated inhibition of insulin‐dependent GLUT4 translocation. In S961‐treated C57BL/6 mice, an in vivo model of insulin resistance and type 2 diabetes, rutin treatment showed a normoglycemic effect in the OGTT. CONCLUSION: This study shows evidence that rutin may serve as a potential agent for glycemic control through enhancement of IRK activity, thereby inducing the insulin signaling pathway causing increased GLUT4 translocation and increased glucose uptake.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or ...bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
During the past few decades, supercritical fluid (SCF) has emerged as an effective alternative for many traditional pharmaceutical manufacturing processes. Operating active pharmaceutical ingredients ...(APIs) alone or in combination with various biodegradable polymeric carriers in high‐pressure conditions provides enhanced features with respect to their physical properties such as bioavailability enhancement, is of relevance to the application of SCF in the pharmaceutical industry. Herein, recent advances in drug delivery systems manufactured using the SCF technology are reviewed. We provide a brief description of the history, principle, and various preparation methods involved in the SCF technology. Next, we aim to give a brief overview, which provides an emphasis and discussion of recent reports using supercritical carbon dioxide (SC‐CO2) for fabrication of polymeric carriers, for applications in areas related to drug delivery, tissue engineering, bio‐imaging, and other biomedical applications. We finally summarize with perspectives.
The supercritical carbon dioxide technology utilizes carbon dioxide in its supercritical state as it is non‐toxic, cost‐effective, and environmental‐friendly. This green technology produces polymeric carriers in various forms by altering critical conditions such as temperature and pressure during the fabrication process. We provide an overview of the history, principle, and preparation methods involving this versatile technology and its use in fabrication of polymeric carriers for applications in drug delivery and related biomedical areas.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit ...effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective
To evaluate human glymphatics and meningeal lymphatics noninvasively.
Methods
This prospective study implemented 3‐dimensional (3D) isotropic contrast‐enhanced T2 fluid‐attenuated inversion ...recovery (CE‐T2‐FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood–brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol/kg 0.2ml/kg) was administered intravenously in all study subjects.
Results
In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para‐arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase‐ or condition‐specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54 minutes and was completely cleared within 18 hours.
Interpretation
This large‐scale in vivo study successfully demonstrated the putative human para‐arterial glymphatic transports and meningeal lymphatics by clear depiction of para‐arterial, parasinus, and paravenous meningeal contrast enrichment using high‐resolution 3D isotropic CE‐T2‐FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111–124
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Many living organisms undergo conspicuous or abrupt changes in body structure, which is often accompanied by a behavioral change. Inspired by the natural metamorphosis, robotic systems can be ...designed as reconfigurable to be multifunctional. Here, a tissue‐engineered transformable robot is developed, which can be remotely controlled to assume different mechanical structures for switching locomotive function. The soft robot is actuated by a muscular tail fin that emulates the swimming of whales and works as a cellular engine powered by the synchronized contraction of striated cardiac microtissue constructs. For a transition of locomotive behavior, the robot can be optically triggered to transform from a spread to a retracted form, which effectively changes the bending stiffness of the tail fins, thus minimizing the propulsion output from the “tail fin” and effectively switching off the engine. With the unprecedented controllability and responsiveness, the transformable robot is implemented to work as a cargo carrier for programmed delivery of chemotherapeutic agents to selectively eradicate cancer cells. It is believed that the realization of the transformable concept paves a pathway for potential development of intelligent biohybrid robotic systems.
A tissue‐engineered transformable robot is developed, which can be remotely controlled to assume different mechanical structures for switching locomotive functionality. With the unprecedented controllability and responsiveness, the transformable robot can be implemented for programmed eradication of cancer cells for instance. This design concept paves the way for the potential development of intelligent biohybrid robotic systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with ...patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
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•N-linked glycosylation of PD-L1 hinders its recognition by PD-L1 antibodies•Removal of glycosylation enhances anti-PD-L1 signal in a variety of bioassays•Patient sample deglycosylation prevents false-negative detection of PD-L1•Deglycosylated PD-L1 is a more reliable biomarker to guide immunotherapy
Histological detection of PD-L1 may guide therapy with anti-PD-1/PD-L1 antibodies but some PD-L1-negative tumors respond to these treatments. Lee et al. show that enzymatic deglycosylation of tissue sections improves PD-L1 detection and its predictive value, and could potentially impact patient stratification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP