Ox-LDL-induced CD80+ macrophages expand pro-atherosclerotic NKT cells via CD1d in atherosclerotic mice and hyperlipidemic patients.

Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear. Our findings demonstrated that there were higher populations of NKT cells and interferon gamma (IFN-γ)-producing NKT cells in the peripheral blood of patients with hyperlipidemia and in the aorta, blood, spleen, and bone marrow of early atherosclerotic mice compared to control groups. Moreover, we discovered that the infiltration of M1 macrophages and CD1d expression on M1 macrophages in atherosclerotic mice climbed remarkably. CD1d expression increased in M1 macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) ex vivo and in vitro. Ex vivo co-culture of macrophages with NKT cells revealed that ox-LDL-induced M1 macrophages presented lipid antigen alpha-galactosylceramide (α-Galcer) to NKT cells via CD1d, enabling NKT cells to express more IFN-γ. Furthermore, a greater proportion of CD1d+monocytes and CD1d+M1 monocytes were found in peripheral blood of hyperlipidemic patients compared with that of healthy donors. Positive correlations were found between CD1d+ M1 monocytes and NKT cells or IFN-γ+ NKT cells in hyperlipidemic patients. Our findings illustrate that M1 macrophages stimulate NKT cells to secret IFN-γ via CD1d presenting α-Galcer, which may accelerate the progression of early atherosclerosis. Inhibiting lipid antigen presentation by M1 macrophages to NKT cells may be a promising immune target for the treatment of early atherosclerosis.

Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics.

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F, in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism. Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10-7 to 1 × 10-5 M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca2+ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension.

How I do it? Preoperative Microsoft HoloLens 2 planning-assisted surgical clipping of a fetal posterior cerebral artery aneurysm.

BACKGROUND: The treatment of intracranial aneurysms has predominantly shifted towards endovascular strategies, but complex cases still necessitate microsurgery. Preoperative stimulation can be beneficial for inexperienced young neurosurgeons in preparing for safe microsurgery. METHOD: A 72-year-old female with a left irregular fetal posterior cerebral artery (PCA) aneurysm underwent clipping repair. Microsoft HoloLens 2, utilizing mixed reality technology, was employed for preoperative stimulation and anatomical study. During the operation, we successfully identified the planned relationship between the aneurysm and the fetal PCA. The patient was cured without any complications. CONCLUSION: We hope that this report will highlight the significance of Microsoft HoloLens 2 in microsurgical planning and education.

Metabolite Neu5Ac triggers SLC3A2 degradation promoting vascular endothelial ferroptosis and aggravates atherosclerosis progression in ApoE-/-mice.

Background: Atherosclerosis (AS) is still the major cause of cardiovascular disease (CVD) as well as stroke. Endothelial metabolic disorder has been found to be activated and then promote endothelial cells (ECs) injury, which is regarded to initiate AS progression. N-acetylneuraminic acid (Neu5Ac), a metabolite produced by hexosamine-sialic acid pathway branching from glucose metabolism, was presented as a notable biomarker of CVD and is positively correlated with ECs function. However, few studies explain whether Neu5Ac regulate AS progression by affecting EC function as well as its involved mechanisms are still unknown. Methods: Here, we mimicked an animal model in ApoE-/- mice which displaying similar plasma Neu5Ac levels with AS model to investigate its effect on AS progression. Results: We found that Neu5Ac exacerbated plaques area and increased lipids in plasma in absence of HFD feeding, and ECs inflammatory injury was supposed as the triggering factor upon Neu5Ac treatment with increasing expression of IL-1ß, ICAM-1, and promoting ability of monocyte adhesion to ECs. Mechanistic studies showed that Neu5Ac facilitated SLC3A2 binding to ubiquitin and then triggered P62 mediated degradation, further leading to accumulation of lipid peroxidation in ECs. Fer-1 could inhibit ECs injury and reverse AS progression induced by Neu5Ac in ApoE-/- mice. Interestingly, mitochondrial dysfunction was also partly participated in ECs injury after Neu5Ac treatment and been reversed by Fer-1. Conclusions: Together, our study unveils a new mechanism by which evaluated metabolite Neu5Ac could promote SLC3A2 associated endothelial ferroptosis to activate ECs injury and AS plaque progression, thus providing a new insight into the role of Neu5Ac-ferroptosis pathway in AS. Also, our research revealed that pharmacological inhibition of ferroptosis may provide a novel therapeutic strategy for premature AS.

Oscillatory shear stress-mediated aberrant O-GlcNAc SIRT3 accelerates glycocalyx inflammatory injury via LKB1/p47phox/Hyal2 signaling.

Glycocalyx coating on endothelial surface layer helps to sense shear forces and maintain endothelial function. However, the underlying mechanism of endothelial glycocalyx degradation upon disordered shear stress stimulation is not fully understood. SIRT3, a major NAD+-dependent protein deacetylases, is required for protein stability during vascular homeostasis and partly involved in atherosclerotic process. While few studies showed that SIRT3 is responsible for endothelial glycocalyx homeostasis under shear stress, the underlying mechanisms remain largely unknown. Here, we demonstrated that oscillatory shear stress (OSS) induces glycocalyx injury by activating LKB1/p47phox/Hyal2 axis both in vivo and in vitro. And O-GlcNAc modification served to prolong SIRT3 deacetylase activity and stabilized p47/Hyal2 complex. OSS could decrease SIRT3 O-GlcNAcylation to activate LKB1, further accelerated endothelial glycocalyx injury in inflammatory microenvironment. SIRT3Ser329 mutation or inhibition of SIRT3 O-GlcNAcylation strongly promoted glycocalyx degradation. On the contrary, overexpression of SIRT3 reverse glycocalyx damage upon OSS treatment. Together, our findings indicated that targeting O-GlcNAcylation of SIRT3 could prevent and/or treat diseases whereby glycocalyx injured.

Novel Effect of p-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets.

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.

Sialic acids promote macrophage M1 polarization and atherosclerosis by upregulating ROS and autophagy blockage.

Accumulating evidence suggests that sialic acids is closely related to atherosclerosis. However, the effects and underlying mechanisms of sialic acids in atherosclerosis have been not defined. Macrophages are one of the most important cells during plaque progression. In this study, we investigated the role of sialic acids in the M1 macrophage polarization and pathogenesis of atherosclerosis. Here we found that sialic acids can promote the polarization of RAW264.7 cells to the M1 phenotype, thereby promoting the expression of proinflammatory cytokines in vitro. The proinflammatory effect of sialic acids may result from the inhibition of LKB1-AMPK-Sirt3 signaling pathway to upregulate intracellular ROS and impairing autophagy-lysosome system to block autophagic flux. In the APOE-/- mice, sialic acids in plasma increased during the development of atherosclerosis. Moreover, exogenous supplement of sialic acids can promote plaque progression in aortic arch and aortic sinus being accompanied by the differentiation of macrophages into M1 type in peripheral tissues. These studies demonstrated that sialic acids can promote macrophage polarization toward the M1 phenotype to accentuate atherosclerosis via inducing mitochondrial ROS and blocking autophagy, thus providing clue to a novel therapeutic strategy for atherosclerosis.

Hypofucosylation of Unc5b regulated by Fut8 enhances macrophage emigration and prevents atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is the leading underlying cause of the majority of clinical cardiovascular events. Retention of foamy macrophages in plaques is the main factor initiating and promoting the atherosclerotic process. Our previous work showed that ox-LDL induced macrophage retention in plaques and that the guidance receptor Uncoordinated-5 homolog B (Unc5b) was involved in this process. However, little is known about the role of Unc5b in regulating macrophage accumulation within plaques. RESULTS: In the present study, we found that Unc5b controls macrophage migration and thus promotes plaque progression in ApoE-/- mice. The immunofluorescence colocalization assay results first suggested that fucosyltransferase 8 (Fut8) might participate in the exacerbation of atherosclerosis. Animals with Unc5b overexpression showed elevated levels of Fut8 and numbers of macrophages and an increased lesion size and intimal thickness. However, these effects were reversed in ApoE-/- mice with Unc5b knockdown. Furthermore, Raw264.7 macrophages with siRNA-mediated silencing of Unc5b or overexpression of Unc5b were used to confirm the regulatory mechanisms of Unc5b and Fut8 in vitro. In response to ox-LDL exposure, Unc5b and Fut8 were both upregulated, and macrophages showed reduced pseudopod formation and migratory capacities. However, these capacities were restored by blocking Unc5b or Fut8. Furthermore, the IP assay indicated that Fut8 regulated the level of α-1,6 fucosylation of Unc5b, which mainly occurs in the endoplasmic reticulum (ER), and genetic deletion of the main fucosylation sites or Fut8 resulted in hypofucosylation of Unc5b. Moreover, the macrophage migration mediated by Unc5b depended on inactivation of the p-CDC42/p-PAK pathway. Conversely, macrophages with Unc5b overexpression displayed activation of the p-CDC42/p-PAK pathway and decreased migration both in vivo and in vitro. CONCLUSION: These results demonstrated that hypofucosylation of Unc5b regulated by Fut8 is positively associated with the delay of the atherosclerotic process by promoting the migration of foamy macrophages. These findings identify a promising therapeutic target for atherosclerosis.

Towards carbon neutrality: A study on China's long-term low-carbon transition pathways and strategies.

As the world's biggest carbon dioxide (CO2) emitter and the largest developing country, China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years. This study fully considered the carbon-neutrality goal and the temperature rise constraints required by the Paris Agreement, by developing six long-term development scenarios, and conducting a quantitative evaluation on the carbon emissions pathways, energy transformation, technology, policy and investment demand for each scenario. This study combined both bottom-up and top-down methodologies, including simulations and analyses of energy consumption of end-use and power sectors (bottom-up), as well as scenario analysis, investment demand and technology evaluation at the macro level (top-down). This study demonstrates that achieving carbon neutrality before 2060 translates to significant efforts and overwhelming challenges for China. To comply with the target, a high rate of an average annual reduction of CO2 emissions by 9.3% from 2030 to 2050 is a necessity, which requires a huge investment demand. For example, in the 1.5 °C scenario, an investment in energy infrastructure alone equivalent to 2.6% of that year's GDP will be necessary. The technological pathway towards carbon neutrality will rely highly on both conventional emission reduction technologies and breakthrough technologies. China needs to balance a long-term development strategy of lower greenhouse gas emissions that meets both the Paris Agreement and the long-term goals for domestic economic and social development, with a phased implementation for both its five-year and long-term plans.

Antigen-Presenting Cell-Like Neutrophils Foster T Cell Response in Hyperlipidemic Patients and Atherosclerotic Mice.

Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis. The roles of APC-like neutrophils and relevant mechanisms were investigated in hyperlipidemic patients and atherosclerotic mice. Higher percentages of neutrophils and APC-like neutrophils were found in peripheral blood of hyperlipidemic patients than that of healthy donors. Meanwhile, we also identified higher infiltration of neutrophils and APC-like neutrophils in atherosclerotic mice. Ox-LDL induced Phorbol-12-myristate-13-acetate (PMA)-activated neutrophils to acquire the APC-like phenotype. Importantly, upon over-expression of APC-like markers, neutrophils acquired APC functions to promote the proliferation and interferon-γ production of CD3+ T cells via HLA-DR/CD80/CD86. In accordance with what found in vitro, positive correlation between neutrophils and CD3+ T cells was observed in hyperlipidemic patients. In conclusion, our work identifies a proinflammatory neutrophil subset in both hyperlipidemic patients and atherosclerotic mice. This unique phenotype of neutrophils could activate the adaptive immune response to promote atherosclerosis progression. Thus, this neutrophil subset may be a new target for immunotherapy of atherosclerosis.

Multicolor Light Mixing in Optofluidic Concave Interfaces for Anticounterfeiting with Deep Learning Authentication.

Anticounterfeiting technology has received tremendous interest for its significance in daily necessities, medical industry, and high-end products. Confidential tags based on photoluminescence are one of the most widely used approaches for their vivid visualization and high throughput. However, the complexity of confidential tags is generally limited to the accessibility of inks and their spatial location; generating an infinite combination of emission colors is therefore a challenging task. Here, we demonstrate a concept to create complex color light mixing in a confined space formed by microscale optofluidic concave interfaces. Infinite color combination and capacity were generated through chaotic behavior of light mixing and interaction in an ininkjet-printed skydome structure. Through the chaotic mixing of emission intensity, wavelength, and light propagation trajectories, the visionary patterns serve as a highly unclonable label. Finally, a deep learning-based machine vision system was built for the authentication process. The developed anticounterfeiting system may provide inspiration for utilizing space color mixing in optical security and communication applications.

Liquid crystal-amplified optofluidic biosensor for ultra-highly sensitive and stable protein assay.

Protein assays show great importance in medical research and disease diagnoses. Liquid crystals (LCs), as a branch of sensitive materials, offer promising applicability in the field of biosensing. Herein, we developed an ultrasensitive biosensor for the detection of low-concentration protein molecules, employing LC-amplified optofluidic resonators. In this design, the orientation of LCs was disturbed by immobilized protein molecules through the reduction of the vertical anchoring force from the alignment layer. A biosensing platform based on the whispering-gallery mode (WGM) from the LC-amplified optofluidic resonator was developed and explored, in which the spectral wavelength shift was monitored as the sensing parameter. The microbubble structure provided a stable and reliable WGM resonator with a high Q factor for LCs. It is demonstrated that the wall thickness of the microbubble played a key role in enhancing the sensitivity of the LC-amplified WGM microcavity. It is also found that protein molecules coated on the internal surface of microbubble led to their interactions with laser beams and the orientation transition of LCs. Both effects amplified the target information and triggered a sensitive wavelength shift in WGM spectra. A detection limit of 1 fM for bovine serum albumin (BSA) was achieved to demonstrate the high-sensitivity of our sensing platform in protein assays. Compared to the detection using a conventional polarized optical microscope (POM), the sensitivity was improved by seven orders of magnitude. Furthermore, multiple types of proteins and specific biosensing were also investigated to verify the potential of LC-amplified optofluidic resonators in the biomolecular detection. Our studies indicate that LC-amplified optofluidic resonators offer a new solution for the ultrasensitive real-time biosensing and the characterization of biomolecular interactions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43074-021-00041-1.

Topological Encoded Vector Beams for Monitoring Amyloid-Lipid Interactions in Microcavity.

Lasers are the pillars of modern photonics and sensing. Recent advances in microlasers have demonstrated its extraordinary lasing characteristics suitable for biosensing. However, most lasers utilized lasing spectrum as a detection signal, which can hardly detect or characterize nanoscale structural changes in microcavity. Here the concept of amplified structured light-molecule interactions is introduced to monitor tiny bio-structural changes in a microcavity. Biomimetic liquid crystal droplets with self-assembled lipid monolayers are sandwiched in a Fabry-Pérot cavity, where subtle protein-lipid membrane interactions trigger the topological transformation of output vector beams. By exploiting Amyloid ß (Aß)-lipid membrane interactions as a proof-of-concept, it is demonstrated that vector laser beams can be viewed as a topology of complex laser modes and polarization states. The concept of topological-encoded laser barcodes is therefore developed to reveal dynamic changes of laser modes and Aß-lipid interactions with different Aß assembly structures. The findings demonstrate that the topology of vector beams represents significant features of intracavity nano-structural dynamics resulted from structured light-molecule interactions.

Light-Harvesting in Biophotonic Optofluidic Microcavities via Whispering-Gallery Modes.

Phycobiliproteins are a class of light-harvesting fluorescent proteins existing in cyanobacteria and microalgae, which harvest light and convert it into electricity. Owing to recent demands on environmental-friendly and renewable apparatuses, phycobiliproteins have attracted substantial interest in bioenergy and sustainable devices. However, converting energy from biological materials remains challenging to date. Herein, we report a novel scheme to enhance biological light-harvesting through light-matter interactions at the biointerface of whispering-gallery modes (WGMs), where phycobiliproteins were employed as the active gain material. By exploiting microdroplets as a carrier for light-harvesting biomaterials, strong local electric field enhancement and photon confinement at the cavity interface resulted in significantly enhanced bio-photoelectricity. A threshold-like behavior was discovered in photocurrent enhancement and the WGM modulated fluorescence. Systematic studies of biologically produced photoelectricity and optical mode resonance were carried out to illustrate the impact of the cavity quality factor, structural geometry, and refractive indices. Finally, a biomimetic system was investigated by exploiting cascade energy transfer in phycobiliprotein assembly composed of three light-harvesting proteins. The key findings not only highlight the critical role of optical cavity in light-harvesting but also offer deep insights into light energy coupling in biomaterials.

Programmable Rainbow-Colored Optofluidic Fiber Laser Encoded with Topologically Structured Chiral Droplets.

Optofluidic lasers are emerging building blocks with immense potential in the development of miniaturized light sources, integrated photonics, and sensors. The capability of on-demand lasing output with programmable and continuous wavelength tunability over a broad spectral range enables key functionalities in wavelength-division multiplexing and manipulation of light-matter interactions. However, the ability to control multicolor lasing characteristics within a small mode volume with high reconfigurability remains challenging. The color gamut is also restricted by the number of dyes and emission wavelength of existing materials. In this study, we introduce a fully programmable multicolor laser by encapsulating organic-dye-doped cholesteric liquid crystal microdroplet lasers in an optofluidic fiber. A mechanism for tuning laser emission wavelengths was proposed by manipulating the topologically induced nanoshell structures in microdroplets with different chiral dopant concentrations. Precision control of distinctive lasing wavelengths and colors covering the entire visible spectra was achieved, including monochromatic lasing, dual-color lasing, tri-color lasing, and white colored lasing with tunable color temperatures. Our findings revealed a CIE color map with 145% more perceptible colors than the standard RGB space, shedding light on the development of programmable lasers, multiplexed encoding, and biomedical detection.

Stimulated Chiral Light-Matter Interactions in Biological Microlasers.

Chiral light-matter interactions have emerged as a promising area in biophysics and quantum optics. Great progress in enhancing chiral light-matter interactions have been investigated through passive resonators or spontaneous emission. Nevertheless, the interaction between chiral biomolecules and stimulated emission remains unexplored. Here we introduce the concept of a biological chiral laser by amplifying chiral light-matter interactions in an active resonator through stimulated emission process. Green fluorescent proteins or chiral biomolecules encapsulated in Fabry-Perot microcavity served as the gain material while excited by either left-handed or right-handed circularly polarized pump laser. Owing to the nonlinear pump energy dependence of stimulated emission, significant enhancement of chiral light-matter interactions was demonstrated. Detailed experiments and theory revealed that a lasing dissymmetry factor is determined by molecular absorption dissymmetry factor at its excitation wavelength. Finally, chirality transfer was investigated under a stimulated emission process through resonance energy transfer. Our findings elucidate the mechanism of stimulated chiral light-matter interactions, providing better understanding of light-matter interaction in biophysics, chiral sensing, and quantum biophotonics.

Interleukin-17-Producing CD4+ T Cells Promote Inflammatory Response and Foster Disease Progression in Hyperlipidemic Patients and Atherosclerotic Mice.

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE-/- mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE-/- mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.

Bioresponsive microlasers with tunable lasing wavelength.

Lasing particles are emerging tools for amplifying light-matter interactions at the biointerface by exploiting its strong intensity and miniaturized size. Recent advances in implementing laser particles into living cells and tissues have opened a new frontier in biological imaging, monitoring, and tracking. Despite remarkable progress in micro- and nanolasers, lasing particles with surface functionality remain challenging due to the low mode-volume while maintaining a high Q-factor. Herein, we report the novel concept of bioresponsive microlasers by exploiting interfacial energy transfer based on whispering-gallery-mode (WGM) microdroplet cavities. Lasing wavelengths were manipulated by energy transfer-induced changes of a gain spectrum resulting from the binding molecular concentrations at the cavity surface. Both protein-based and enzymatic-based interactions were demonstrated, shedding light on the development of functional microlasers. Finally, tunable lasing wavelengths over a broad spectral range were achieved by selecting different donor/acceptor pairs. This study not only opens new avenues for biodetection, but also provides deep insights into how molecules modulate laser light at the biointerface, laying the foundation for the development of smart bio-photonic devices at the molecular level.

Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation.

Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP's protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx.