A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy.

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated AKT, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of mitophagy through the AKT/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

The interactions between CpG oligodeoxynucleotides and Toll-like receptors in Pacific white shrimp Litopenaeus vannamei.

CpG oligodeoxynucleotides (ODNs), as a novel type of adjuvant with immunomodulatory effects, are recognized by Toll-like receptors (TLRs) in Litopenaeus vannamei. In the present study, eleven LvTLRs-pCMV recombinants (rLvTLRs) were constructed to investigate the relationships between various CpG ODNs and different LvTLRs in human embryonic kidney 293T (HEK293T) cells, which was further confirmed by bio-layer interferometry (BLI) technique. The results of dual luciferase reporter assay showed that every LvTLR could activate multiple downstream genes, mainly including NF-κB, CREB, ISRE, IL-6-promoter, TNF-α-promoter and Myc, thereby inducing main signaling pathways in shrimps. Most CpG ODNs possessed affinities to more than one LvTLR, while each LvTLR could recognize multiple CpG ODNs, and the widely recognized ligands within CpG ODNs are A-class and B-class. Moreover, BLI analysis showed that CpG 2216, Cpg 2006, CpG 2143 and CpG 21425 exhibited dose-dependent affinity to the expressed TLR protein, which were consistent with the results in HEK293T cells. It suggested that the interactions of CpG ODNs with LvTLRs were indispensable for the immune regulation triggered by CpG ODNs, and these findings would lay foundations for studying the activations of LvTLRs to immune signaling pathways and shedding lights on the immune functions and mechanisms of CpG ODNs.

Tobacco toxins induce osteoporosis through ferroptosis.

Clinical epidemiological studies have confirmed that tobacco smoking disrupts bone homeostasis and is an independent risk factor for the development of osteoporosis. The low viability and inferior osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) are important etiologies of osteoporosis. However, few basic studies have elucidated the specific mechanisms that tobacco toxins devastated BMSCs and consequently induced or exacerbated osteoporosis. Herein, our clinical data showed the bone mineral density (BMD) values of femoral neck in smokers were significantly lower than non-smokers, meanwhile cigarette smoke extract (CSE) exposure led to a significant decrease of BMD in rats and dysfunction of rat BMSCs (rBMSCs). Transcriptomic analysis and phenotype experiments suggested that the ferroptosis pathway was significantly activated in CSE-treated rBMSCs. Accumulated intracellular reactive oxygen species activated AMPK signaling, furtherly promoted NCOA4-mediated ferritin-selective autophagic processes, increased labial iron pool and lipid peroxidation deposition, and ultimately led to ferroptosis in rBMSCs. Importantly, in vivo utilization of ferroptosis and ferritinophagy inhibitors significantly alleviated BMD loss in CSE-exposed rats. Our study innovatively reveals the key mechanism of smoking-related osteoporosis, and provides a possible route targeting on the perspective of BMSC ferroptosis for future prevention and treatment of smoking-related bone homeostasis imbalance.

Quercetin promotes autophagy to alleviate cigarette smoke-related periodontitis.

BACKGROUND AND OBJECTIVES: Cigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke-related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant-derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism. METHODS: The cigarette smoke-related ligature-induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro-computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit-8, and oxidative stress levels were tested by 2,7-dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism. RESULTS: Alveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin-1 thus to promote autophagy and reduce oxidative stress damage. CONCLUSION: Our results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE-induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.

Molecular cloning and characterization of a thioredoxin-like protein gene in rotifer Brachionus plicatilis.

The thioredoxin-like protein exists widely, in various organisms, as a regulator of redox homeostasis. In this study, the full-length cDNA of a thioredoxin-like protein gene from rotifer Brachionus plicatilis (designated as BpTXNL) was obtained by 5' rapid amplification of cDNA end (RACE) technology. The complete cDNA of BpTXNL was 1111 bp, and contained a 5' untranslated region (UTR) of 69 bp, a 3' UTR of 163 bp with a polyadenylate additional signal and a polyadenylation site (PAS), and an open reading frame (ORF) of 878 bp, encoding 292 amino acids. The calculated molecular weight and the theoretical isoelectric point (pI) of the deduced BpTXNL peptide were 32.7 kDa and 4.97, respectively. The deduced protein sequence of BpTXNL contained a thioredoxin domain with the conserved redox-active site at 33CGPC36 and a proteasome-interacting thioredoxin (PITH) domain. Phylogenetic analysis demonstrated that BpTXNL was clustered with TXNLs of Strongyloides ratti and Caenorhabditis elegans. The temporal mRNA expression level of BpTXNL significantly decreased at 6 h, then increased to the peak 24h after the 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) challenge, while the mRNA transcripts of BpTXNL significantly increased and reached the peaks twice, at 6 h and 24 h after the lipopolysaccharide (LPS) challenge. The recombinant BpTXNL protein quickly exhibited a concentration-dependent antioxidant capacity and the peak occurred at 55 min in the 20 µM group. All these results showed that BpTXNL possesses an antioxidant capacity, and that it may be involved in the regulation of excessive reactive oxygen species (ROS) during environmental stress or pathogen invading.

Cellular Features Revealed by Transverse Laser Modes in Frequency Domain.

Biological lasers which utilize Fabry-Pérot (FP) cavities have attracted tremendous interest due to their potential in amplifying subtle biological changes. Transverse laser modes generated from cells serve as distinct fingerprints of individual cells; however, most lasing signals lack the ability to provide key information about the cell due to high complexity of transverse modes. The missing key, therefore, hinders it from practical applications in biomedicine. This study reveals the key mechanism governing the frequency distributions of transverse modes in cellular lasers. Spatial information of cells including curvature can be interpreted through spectral information of transverse modes by means of hyperspectral imaging. Theoretical studies are conducted to explore the correlation between the cross-sectional morphology of a cell and lasing frequencies of transverse modes. Experimentally, the spectral characteristics of transverse modes are investigated in live and fixed cells with different morphological features. By extracting laser modes in frequency domain, the proposed concept is applied for studying cell adhesion process and cell classification from rat cortices. This study expands a new analytical dimension of cell lasers, opening an avenue for subcellular analysis in biophotonic applications.

Enzyme-Programmable Microgel Lasers for Information Encoding and Anti-Counterfeiting.

Microscale laser emissions have emerged as a promising approach for information encoding and anti-counterfeiting for their feature-rich spectra and high sensitivity to the surrounding environment. Compared with artificial materials, natural responsive biomaterials enable a higher level of complexity and versatile ways for tailoring optical responses. However, precise control of lasing wavelengths and spatial locations with biomolecules remains a huge challenge. Here, a biologically programmable laser, in which the lasing can be manipulated by biomolecular activities at the nanoscale, is developed. Tunable lasing wavelengths are achieved by exploiting the swelling properties of enzyme-responsive hydrogel droplets in a Fabry-Pérot microcavity. Both experimental and theoretical means demonstrate that inner 3D network structures and external curvature of the hydrogel droplets lead to different lasing thresholds and resonance wavelengths. Finally, inkjet-printed multiwavelength laser encoding and anti-counterfeiting are showcased under different scalabilities and environments. Hyperspectral laser images are utilized as an advanced feature for a higher level of security. The biologically encoded laser will provide a new insight into the development of biosynthetic and bioprogrammable laser devices, offering new opportunities for secure communication and smart sensing.

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.

Imaging-Based Optofluidic Biolaser Array Encapsulated with Dynamic Living Organisms.

Optofluidic biolasers have emerged as promising tools for biomedical analysis due to their strong light-matter interactions and miniaturized size. Recent developments in optofluidic lasers have opened a new Frontier in monitoring biological processes. However, most biolasers require precise recording of the lasing spectrum at the single cavity level, which limits its application in high-throughput applications. Herein, a microdroplet laser array encapsulated with living Escherichia coli was printed on highly reflective mirrors, where laser emission images were employed to reflect the dynamic changes in living organisms. The concept of image-based lasing analysis was proposed by quantifying the integrated pixel intensity of the lasing image from whispering-gallery modes. Finally, dynamic interactions between E. coli and antibiotic drugs were compared under fluorescence and laser emission images. The amplification that occurred during laser generation enabled the quantification of tiny biological changes in the gain medium. Laser imaging presented a significant increase in integrated pixel intensity by 2 orders of magnitude. Our findings demonstrate that image-based lasing analysis is more sensitive to dynamic changes than fluorescence analysis, paving the way for high-throughput on-chip laser analysis of living organisms.

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.

DNA Self-Switchable Microlaser.

Advances in switchable microlasers have emerged as a building block with immense potential in controlling light-matter interactions and integrated photonics. Compared to artificially designed interfaces, a stimuli-responsive biointerface enables a higher level of functionalities and versatile ways of tailoring optical responses at the nanoscale. However, switching laser emission with biological recognition has yet to be addressed, particularly with reversibility and wavelength tunability over a broad spectral range. Here we demonstrate a self-switchable laser exploiting the biointerface between label-free DNA molecules and dye-doped liquid crystal matrix in a Fabry-Perot microcavity. Laser emission switching among different wavelengths was achieved by utilizing DNA conformation changes as the switching power, which alters the orientation of the liquid crystals. Our findings demonstrate that different concentrations of single-stranded DNA lead to different temporal switching of lasing wavelengths and intensities. The lasing wavelength could be reverted upon binding with the complementary sequence through DNA hybridization process. Both experimental and theoretical studies revealed that absorption strength is the key mechanism accounting for the laser shifting behavior. This study represents a milestone in achieving a biologically controlled laser, shedding light on the development of programmable photonic devices at the sub-nanoscale by exploiting the complexity and self-recognition of biomolecules.

Microalgae living sensor for metal ion detection with nanocavity-enhanced photoelectrochemistry.

Metal ions are known to play various roles in living organisms; therefore, the detection of metal ions in water resources is essential for monitoring health and environmental conditions. In contrast to artificially fabricated materials and devices, biological-friendly materials such as microalgae have been explored for detecting toxic chemicals by employing fluorescence emissions and biophotovoltaic fuel cells. However, complicated fabrication, long measurement time, and low sensitivity remain the greatest challenge due to the minimal amount of bioelectricity generated from whole-cell microalgae. Herein we report the novel concept of a microalgae living biosensor by enhancing photocurrent through nanocavities formed between copper (Cu) nanoparticles and the Cu-electrode beneath. The strong energy coupling between plasmon cavity modes and excited photosynthetic fluorescence from Chlorella demonstrated that photoelectrical efficiency could be significantly amplified by more than two orders of magnitude through nanocavity confinement. Simulation results reveal that substantial near-field enhancements could help confine the electric field to the electrodes. Finally, the microalgae sensor was exploited to detect various light and heavy metal ions with a breakthrough detection limit of 50 nM. This study is envisioned to provide inspirational insights on nanocavity-enhanced electrochemistry, opening new routes for biochemical detection, water monitoring, and sustainable optoelectronics.

Bio-electrostatic sensitive droplet lasers for molecular detection.

Electrostatics plays a critical function in most biomolecules, therefore monitoring molecular electrostatic interactions at the biointerface can provide the basis in diagnosis and biomedical science. Herein we report a bioelectrostatic responsive microlaser based on liquid crystal (LC) droplets and explored its application for the ultrasensitive detection of negatively charged biomolecules. A whispering gallery mode (WGM) laser from positively charged LC microdroplets was designed as the optical resonator, in which the lasing wavelength shift was employed as the sensing parameter. We verified that molecular electrostatic changes at the biointerface of the droplet trigger a wavelength shift in laser spectra. Compared to a conventional polarized optical microscope, a significantly improved sensitivity and dynamic range by four orders of magnitude were achieved. Our results helped discover that the surface-to-volume ratio plays a critical role in the detection sensitivity in WGM laser-based microsensors. Finally, bovine serum albumin and specific biosensing were exploited to demonstrate the potential applications of microlasers with a detection limit in the order of 1 pM, thus offering new alternatives for ultrasensitive label-free biosensing and monitoring of molecular interactions.