Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Silicone Bioadhesive with Shear-Stiffening Effect: Rate-Responsive Adhesion Behavior and Wound Dressing Application.

Stimuli-responsive adhesives with on-demand adhesion capabilities are highly advantageous for facilitating wound healing. However, the triggering conditions of stimuli-responsive adhesives are cumbersome, even though some of them are detrimental to the adhesive and adjacent natural tissues. Herein, a novel stimuli-responsive adhesive called shear-stiffening adhesive (SSA) has been created by constructing a poly(diborosiloxane)-based silicone network for the first time, and SSA exhibits a rate-responsive adhesion behavior. Furthermore, we introduced bactericidal factors (PVP-I) into SSA and applied it as a wound dressing to promote the healing of infected wounds. Impressively, the wound dressing not only has excellent biocompatibility and long-term antibacterial properties but also performs well in accelerating wound healing. Therefore, this study provides a new strategy for the synthesis of intelligent adhesives with force rate response, which simplifies the triggering conditions by the force rate. Thus, SSA has great potential to be applied in wound management as an intelligent bioadhesive with on-demand adhesion performance.

Turbocharging as a strategy to boost extended perforator flap vascularity in head and neck reconstruction-A report of two cases.

Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.

Triboelectric Nanogenerators Assembled by Cobalt(II) Coordination Polymer Incorporated Composite Films and their Application for Self-Powered Anticorrosion.

A friction layer with stability and durability is important to promote the practical application of triboelectric nanogenerators (TENGs). In this work, a two-dimensional cobalt coordination polymer (Co-CP) was successfully synthesized using cobalt nitrate, 4,4',4''-tricarboxyltriphenylamine and 2,2'-bipyridine. To clearly clarify the effect of the doping proportions of Co-CP and the types of composite polymers on the output performance of the TENG, Co-CP was combined with two organic polymers having different polarities (polyvinylidene fluoride (PVDF) and ethyl cellulose (EC)) to form a series of composite films, which were used as the friction electrode materials to fabricate TENGs. Electrical characterizations indicated that a high output current and voltage were obtained from the TENG based on 15 wt.% Co-CP incorporated in PVDF (Co-CP@PVDF), which could be further improved by the Co-CP@EC composite film at the same doping ratio. Furthermore, the optimally fabricated TENG was demonstrated to prevent electrochemical corrosion of carbon steel.

Behavioral and brain- transcriptomic synchronization between the two opponents of a fighting pair of the fish Betta splendens.

Conspecific male animals fight for resources such as food and mating opportunities but typically stop fighting after assessing their relative fighting abilities to avoid serious injuries. Physiologically, how the fighting behavior is controlled remains unknown. Using the fighting fish Betta splendens, we studied behavioral and brain-transcriptomic changes during the fight between the two opponents. At the behavioral level, surface-breathing, and biting/striking occurred only during intervals between mouth-locking. Eventually, the behaviors of the two opponents became synchronized, with each pair showing a unique behavioral pattern. At the physiological level, we examined the expression patterns of 23,306 brain transcripts using RNA-sequencing data from brains of fighting pairs after a 20-min (D20) and a 60-min (D60) fight. The two opponents in each D60 fighting pair showed a strong gene expression correlation, whereas those in D20 fighting pairs showed a weak correlation. Moreover, each fighting pair in the D60 group showed pair-specific gene expression patterns in a grade of membership analysis (GoM) and were grouped as a pair in the heatmap clustering. The observed pair-specific individualization in brain-transcriptomic synchronization (PIBS) suggested that this synchronization provides a physiological basis for the behavioral synchronization. An analysis using the synchronized genes in fighting pairs of the D60 group found genes enriched for ion transport, synaptic function, and learning and memory. Brain-transcriptomic synchronization could be a general phenomenon and may provide a new cornerstone with which to investigate coordinating and sustaining social interactions between two interacting partners of vertebrates.

Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.

Galectin-7 promotes proliferation and wound healing capacities in periodontal ligament fibroblasts by activating ERK signaling.

Periodontitis is a progressive inflammation condition and a primary cause of tooth loss in adults. As one of the abundant cell types in the periodontium, periodontal ligament fibroblasts (PDLFs) play an integral role in the maintenance and regeneration of periodontal tissue. Our previous work has shown that the application of Er:YAG laser increased the cell proliferation and migratory capacity of PDLFs via induction of galectin-7. In the present study, we aimed to evaluate if the forced expression of galectin-7 directly affected the cellular phenotypes of PDLFs. Our results showed that the cell proliferation, transwell migration, invasion, and wound healing capacities were all upregulated in PDLFs with the ectopic expression of galectin-7. These results suggest that therapeutic approaches to enhance the expression of galectin-7 in periodontium may accelerate tissue regeneration by recruiting more PDLFs to the injured site.

Dysfunction of the 4-coumarate:coenzyme A ligase 4CL4 impacts aluminum resistance and lignin accumulation in rice.

The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross-link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA-mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4-coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4-coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al-induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall.

Reconstruction of the orbital floor using supercritical CO2 decellularized porcine bone graft.

Orbital floor fractures subsequently lead to consequences such as diplopia and enophthalmos. The graft materials used in orbital floor fractures varied from autografts to alloplastic grafts, which possess certain limitations. In the present study, a novel porcine bone matrix decellularized by supercritical CO2 (scCO2), ABCcolla® Collagen Bone Graft, was used for the reconstruction of the orbital framework. The study was approved by the institutional review board (IRB) of Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH). Ten cases underwent orbital floor reconstruction in KMUH in 2019. The orbital defects were fixed by the implantation of the ABCcolla® Collagen Bone Graft. Nine out of ten cases used 1 piece of customized ABCcolla® Collagen Bone Graft in each defect. The other case used 2 pieces of customized ABCcolla® Collagen Bone Graft in one defect area due to the curved outline of the defect. In the outpatient clinic, all 10 cases showed improvement of enophthalmos on CT (computerized tomography) at week 8 follow-up. No replacement of implants was needed during follow-ups. To conclude, ABCcolla® Collagen Bone Graft proved to be safe and effective in the reconstruction of the orbital floor with high accessibility, high stability, good biocompatibility, low infection rate and low complication rate.

Biomechanical analysis of subcondylar fracture fixation using miniplates at different positions and of different lengths.

BACKGROUND: Many types of titanium plates were used to treat subcondylar fracture clinically. However, the efficacy of fixation in different implant positions and lengths of the bone plate has not been thoroughly investigated. Therefore, the primary purpose of this study was to use finite element analysis (FEA) to analyze the biomechanical effects of subcondylar fracture fixation with miniplates at different positions and lengths so that clinicians were able to find a better strategy of fixation to improve the efficacy and outcome of treatment. METHODS: The CAD software was used to combine the mandible, miniplate, and screw to create seven different FEA computer models. These models with subcondylar fracture were fixed with miniplates at different positions and of different lengths. The right unilateral molar clench occlusal mode was applied. The observational indicators were the reaction force at the temporomandibular joint, von Mises stress of the mandibular bone, miniplate and screw, and the sliding distance on the oblique surface of the fracture site at the mandibular condyle. RESULTS: The results showed the efficacy of fixation was better when two miniplates were used comparing to only one miniplates. Moreover, using longer miniplates for fixation had better results than the short one. Furthermore, fixing miniplates at the posterior portion of subcondylar region would have a better fixation efficacy and less sliding distance (5.46-5.76 µm) than fixing at the anterolateral surface of subcondylar region (6.10-7.00 µm). CONCLUSION: Miniplate fixation, which was placed closer to the posterior margin, could effectively reduce the amount of sliding distance in the fracture site, thereby achieving greater stability. Furthermore, fixation efficiency was improved when an additional miniplate was placed at the anterior margin. Our study suggested that the placement of miniplates at the posterior surface and the additional plate could effectively improve stability.

Hyaluronic Acid-Pluronic®F127-Laden Soft Contact Lenses for Corneal Epithelial Healing: In Vitro and In Vivo Studies.

Hyaluronic acid (HA) is widely used to treat various ocular diseases like dry eye syndrome, keratoconus, and other corneal epithelial injuries. The currently available eye drop solutions need frequent doses affecting the routine life style of patients. In this work, the silicone contact lens was designed to entrap HA and Pluronic®F127 to improve the wettability of the contact lens to treat various ocular diseases. The soaking method (HA-SM) was compared with the direct entrapment (DL-HA-PI) technique. The HA-Pluronic®F127-laden contact lenses (DL-HA-PI) showed acceptable optical transmittance with improved swelling (water content) properties. The in vitro release data showed high burst release with HA-SM contact lenses (12-36 h), while DL-HA-PI contact lenses showed prolong release up to 96 h. The in vivo release in the rabbit tear fluid showed high HA concentration (tear fluid) with DL-HA-PI contact lenses in comparison to the HA-SM contact lenses. The DL-HA-PI-3 batch with Pluronic®F127 showed more promising results in schirmer strip study in comparison to DL-HA-3 batch (without Pluronic®F127). The presence of Pluronic®F127 with HA showed high potential to improve hydration property of the contact lens. The corneal healing model showed reduction in the ocular inflammatory symptoms with DL-HA-PI-3 batch, thus demonstrating the potential of HA and Pluronic®F127 to be used in various ocular diseases.

New ingol-type diterpenes from the latex of Euphorbia resinifera.

Two new ingol-type diterpenes, euphoresins A-B (1-2), have been isolated from the methanol extract of Euphorbium, the latex of Euphorbia resinifera Berg. Their structures were established on the basis of extensive analyses of their HR-ESI-MS, IR, UV, 1D, and 2D NMR spectra. The absolute configurations were confirmed by Mosher's method and circular dichroism (CD) analyses. The two compounds were tested for their cytotoxic activities against MCF-7, U937, and C6 cancer cell lines, but they both exhibited little cytotoxic effect.

Synthetic Polymer Affinity Ligand for Bacillus thuringiensis ( Bt) Cry1Ab/Ac Protein: The Use of Biomimicry Based on the Bt Protein-Insect Receptor Binding Mechanism.

We report a novel strategy for creating abiotic Bacillus thuringiensis ( Bt) protein affinity ligands by biomimicry of the recognition process that takes place between Bt Cry1Ab/Ac proteins and insect receptor cadherin-like Bt-R1 proteins. Guided by this strategy, a library of synthetic polymer nanoparticles (NPs) was prepared and screened for binding to three epitopes 280FRGSAQGIEGS290, 368RRPFNIGINNQQ379 and 436FRSGFSNSSVSIIR449 located in loop α8, loop 2 and loop 3 of domain II of Bt Cry1Ab/Ac proteins. A negatively charged and hydrophilic nanoparticle (NP12) was found to have high affinity to one of the epitopes, 368RRPFNIGINNQQ379. This same NP also had specific binding ability to both Bt Cry1Ab and Bt Cry1Ac, proteins that share the same epitope, but very low affinity to Bt Cry2A, Bt Cry1C and Bt Cry1F closely related proteins that lack epitope homology. To locate possible NP- Bt Cry1Ab/Ac interaction sites, NP12 was used as a competitive inhibitor to block the binding of 865NITIHITDTNNK876, a specific recognition site in insect receptor Bt-R1, to 368RRPFNIGINNQQ379. The inhibition by NP12 reached as high as 84%, indicating that NP12 binds to Bt Cry1Ab/Ac proteins mainly via 368RRPFNIGINNQQ379. This epitope region was then utilized as a "target" or "bait" for the separation and concentration of Bt Cry1Ac protein from the extract of transgenic Bt cotton leaves by NP12. This strategy, based on the antigen-receptor recognition mechanism, can be extended to other biotoxins and pathogen proteins when designing biomimic alternatives to natural protein affinity ligands.

Dual-Responsive SPMA-Modified Polymer Photonic Crystals and Their Dynamic Display Patterns.

Light and electrothermal responsive polymer photonic crystals (PCs) modified with 1'-acryloyl chloride-3',3'-dimethyl-6-nitro-spiro(2H-1-benzopyran-2,2'-indoline) (SPMA) are proposed, and their dynamic display patterns are achieved through the combination of the SPMA-modified PCs and a patterned graphite layer. These PCs exhibit fluorescence under UV light irradiation because of the isomerization of the SPMA, which is restricted in the shell of the polymer colloidal spheres. After a voltage is applied to the patterned graphite layer, the fluorescence of PCs in the specific area disappears, and dynamic display patterns are obtained. Under UV light irradiation, the PCs change from the "partial-fluorescence" state to the initial "fluorescence" state, and the patterns disappear. Using this technique, the PC pattern "M L N" on the glass substrate and PC patterns from "0" to "9" on the paper substrate are fabricated. Thus, these dual-responsive PCs have potential applications in information recording, anticounterfeiting, dynamic display, and photoelectric devices.

[Triterpenoids from Uygur medicine latex of Euphorbia resinifera].

Ten triterpenes compounds were isolated from the methanol extraction of the latex of Euphorbia resinifera by means of various chromatographic methods such as silica gel, ODS and semi-preparative HPLC, Their structures were identified by spectroscopic methods and physicochemical properties. These isolated compounds were identified as 3ß-hydroxy-25,26,27-trinor eupha-8-ene-24-oate (1), iso-maticadienediol (2), 25,26,27-trinorTirucall-8-ene-3ß-ol-4-acid (3), dammarendiol Ⅱ (4), eupha-8,24-diene-3-ol-26-al (5), lnonotusane C (6), eupha-8,24-diene-3ß-ol-7,11-dione (7), inoterpene A (8), inoterpene B (9), and eupha-24-methylene-8-ene-3ß-ol-7,11-dione (10). Among them, compound 1 was a new natural product, compounds 2-4 were firstly isolated from the Euphorbiaceae and compounds 5 and 6 were isolated from the genus Euphorbia for the first time. The cytotoxicity of the compounds 1-10 against MCF-7, U937 and C6 cancer cell lines was evaluated, but none of the compounds was active.

Manganese-enhanced degradation of lignocellulosic waste by Phanerochaete chrysosporium: evidence of enzyme activity and gene transcription.

Lignolytic fungi initiate lignocellulose decay by producing extracellular oxidative enzymes. For better understanding the enzymatic degradation of lignocellulose by white-rot fungi, we investigated the effect of manganese on the organic matter loss, manganese peroxidase (MnP) activity, and manganese peroxidase gene (mnp) transcription levels during solid-state fermentation of rice straw with Phanerochaete chrysosporium. The results showed that the addition of manganese improved MnP activity and made it reach the peak earlier, promoted fungal growth at the early period (0-9 days), and enhanced the degradation of lignocellulosic waste. The total organic matter loss had a good correlation with fungal biomass during 30 days of cultivation, and manganese amendment promoted the ability of P. chrysosporium to degrade lignocellulose. Quantitative real-time RT-PCR revealed the differential expression of mnp1, mnp2, and mnp3: manganese amendment increased the transcription of mnp1 and mnp2 but not mnp3. The results indicated that manganese stimulated mnp transcription levels and played a post-transcriptional role in MnP production. These findings provide opportunity of development in enzymatic degradation of lignocellulosic waste by P. chrysosporium amended with manganese.

Extraction and characterization of wax from sugarcane bagasse and the enzymatic hydrolysis of dewaxed sugarcane bagasse.

Extraction of high-value products from agricultural wastes is an important component for sustainable bioeconomy development. In this study, wax extraction from sugarcane bagasse was performed and the beneficial effect of dewaxing pretreatment on the enzymatic hydrolysis was investigated. About 1.2% (w/w) of crude sugarcane wax was obtained from the sugarcane bagasse using the mixture of petroleum ether and ethanol (mass ratio of 1:1) as the extraction agent. Results of Fourier-transform infrared characterization and gas chromatography-mass spectrometry qualitative analysis showed that the crude sugarcane wax consisted of fatty fractions (fatty acids, fatty aldehydes, hydrocarbons, and esters) and small amount of lignin derivatives. In addition, the effect of dewaxing pretreatment on the enzymatic hydrolysis of sugarcane bagasse was also investigated. The digestibilities of cellulose and xylan in dewaxed sugarcane bagasse were 18.7 and 10.3%, respectively, compared with those of 13.1 and 8.9% obtained from native sugarcane bagasse. The dewaxed sugarcane bagasse became more accessible to enzyme due to the disruption of the outermost layer of the waxy materials.

Efficient bioconversion from acid hydrolysate of waste oleaginous yeast biomass after microbial oil extraction to bacterial cellulose by Komagataeibacter xylinus.

Biomass acid hydrolysate of oleaginous yeast Trichosporon cutaneum after microbial oil extraction was applied as substrate for bacterial cellulose (BC) production by Komagataeibacter xylinus (also named as Gluconacetobacter xylinus previously) for the first time. BC was synthesized in static culture for 10 days, and the maximum BC yield (2.9 g/L) was got at the 4th day of fermentation. Most carbon sources in the substrate (glucose, mannose, formic acid, acetic acid) can be utilized by K. xylinus. The highest chemical oxygen demand (COD) removal (40.7 ± 3.0%) was obtained at the 6th day of fermentation, and then the COD increased possibly due to the degradation of BC. The highest BC yield on COD consumption was 38.7 ± 4.0% (w/w), suggesting that this is one efficient bioconversion for BC production. The BC structure was affected little by the substrate by comparison with that generated in classical HS medium using field-emission scanning electron microscope (FE-SEM), Fourier transform infrared, and X-ray diffraction. Overall, this technology can both solve the issue of waste oleaginous yeast biomass and produce valuable biopolymer (BC).

Bacterial cellulose production from the litchi extract by Gluconacetobacter xylinus.

Although litchi has both nutrient and edible value, the extremely short preservation time limited its further market promotion. To explore processed litchi products with longer preservation time, litchi extract was selected as an alternative feedstock for production of bacterial cellulose (BC). After 2 weeks of static fermentation, 2.53 g/L of the BC membrane was obtained. The trace elements including magnesium (Mg) and sodium (Na) in the litchi extract were partly absorbed in the BC membrane, but no potassium (K) element was detected in it, curiously. Scanning electron microscope (SEM) photographs exhibited an ultrafine network nanostructure for the BC produced in the litchi extract. Analysis of the fourier-transform infrared spectroscopy (FTIR) confirmed the pellicles to be a cellulosic material. Interestingly, X-ray diffraction (XRD) results showed the BC membrane obtained from litchi extract had higher crystallinity of 94.0% than that from HS medium. Overall, the work showed the potential of producing high value-added polymer from litchi resources.

High Performance Photoluminescent Carbon Dots for In Vitro and In Vivo Bioimaging: Effect of Nitrogen Doping Ratios.

Photoluminescent carbon dots (CDs) have received ever-increasing attention in the application of optical bioimaging because of their low toxicity, tunable fluorescent properties, and ultracompact size. We report for the first time on enhanced photoluminescence (PL) performance influenced by structure effects among the various types of nitrogen doped (N-doped) PL CDs. These CDs were facilely synthesized from condensation carbonization of linear polyethylenic amine (PEA) analogues and citric acid (CA) of different ratios. Detailed structural and property studies demonstrated that either the structures or the molar ratio of PEAs altered the PL properties of the CDs. The content of conjugated π-domains with C═N in the carbon backbone was correlated with their PL Quantum Yield (QY) (up to 69%). The hybridization between the surface/molecule state and the carbon backbone synergistically affected the chemical/physical properties. Also, long-chain polyethylenic amine (PEA) molecule-doped CDs exhibit increasing photostability, but at the expense of PL efficiency, proving that the PL emission of high QY CDs arise not only from the sp(2)/sp(3) carbon core and surface passivation of CDs, but also from the molecular fluorophores integrated in the CDs. In vitro and in vivo bioimaging of these N-doped CDs showed strong photoluminescence signals. Good biocompatibility demonstrates their potential feasibility for bioimaging applications. In addition, the overall size profile of the as-prepared CDs is comparable to the average size of capillary pores in normal living tissues (∼5 nm). Our study provides valuable insights into the effects of the PEA doping ratios on photoluminescence efficiency, biocompatibility, cellular uptake, and optical bioimaging of CDs.