Sensory nerve regulates progenitor cells via FGF-SHH axis in tooth root morphogenesis.

Nerves play important roles in organ development and tissue homeostasis. Stem/progenitor cells differentiate into different cell lineages responsible for building the craniofacial organs. The mechanism by which nerves regulate stem/progenitor cell behavior in organ morphogenesis has not yet been comprehensively explored. Here, we use tooth root development in mouse as a model to investigate how sensory nerves regulate organogenesis. We show that sensory nerve fibers are enriched in the dental papilla at the initiation of tooth root development. Through single cell RNA-sequencing analysis of the trigeminal ganglion and developing molar, we reveal several signaling pathways that connect the sensory nerve with the developing molar, of which FGF signaling appears to be one of the important regulators. Fgfr2 is expressed in the progenitor cells during tooth root development. Loss of FGF signaling leads to shortened roots with compromised proliferation and differentiation of progenitor cells. Furthermore, Hh signaling is impaired in Gli1-CreER;Fgfr2fl/fl mice. Modulation of Hh signaling rescues the tooth root defects in these mice. Collectively, our findings elucidate the nerve-progenitor crosstalk and reveal the molecular mechanism of the FGF-SHH signaling cascade during tooth root morphogenesis.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Comparative transcriptomic analysis of salivary glands between the zoophytophagous Cyrtorhinus lividipennis and the phytozoophagous Apolygus lucorum.

BACKGROUND: Saliva plays a crucial role in shaping the feeding behavior of insects, involving processes such as food digestion and the regulation of interactions between insects and their hosts. Cyrtorhinus lividipennis serves as a predominant natural enemy of rice pests, while Apolygus lucorum, exhibiting phytozoophagous feeding behavior, is a destructive agricultural pest. In this study, a comparative transcriptome analysis, incorporating the published genomes of C.lividipennis and A.lucorum, was conducted to reveal the role of salivary secretion in host adaptation. RESULTS: In contrast to A.lucorum, C.lividipennis is a zoophytophagous insect. A de novo genome analysis of C.lividipennis yielded 19,706 unigenes, including 16,217 annotated ones. On the other hand, A.lucorum had altogether 20,111 annotated genes, as obtained from the published official gene set (20,353 unigenes). Functional analysis of the top 1,000 salivary gland (SG)-abundant genes in both insects revealed that the SG was a dynamically active tissue engaged in protein synthesis and secretion. Predictions of other tissues and signal peptides were compared. As a result, 94 and 157 salivary proteins were identified in C.lividipennis and A.lucorum, respectively, and were categorized into 68 and 81 orthogroups. Among them, 26 orthogroups were shared, potentially playing common roles in digestion and detoxification, including several venom serine proteases. Furthermore, 42 and 55 orthogroups were exclusive in C.lividipennis and A.lucorum, respectively, which were exemplified by a hyaluronidase in C.lividipennis that was associated with predation, while polygalacturonases in A.lucorum were involved in mesophyll-feeding patterns. CONCLUSIONS: Findings in this study provide a comprehensive insight into saliva secretions in C.lividipennis and A.lucorum via a transcriptome approach, reflecting the intricate connections between saliva secretions and feeding behaviors. It is found that conserved salivary secretions are involved in shaping the overlapping feeding patterns, while a plethora of unique salivary secretions may drive the evolution of specific feeding behaviors crucial for their survival. These results enhance our understanding of the feeding mechanisms in different insects from the perspective of saliva and contribute to future environmentally friendly pest control by utilizing predatory insects.

Falcon Probe: A High-Pressure and Robust Sampling Interface for Coupling Lossless Liquid Chromatography Injection with In Situ Nanoliter-Scale Sample Pretreatment.

With the increasing demand for trace sample analysis, injecting trace samples into liquid chromatography-mass spectrometry (LC-MS) systems with minimal loss has become a major challenge. Herein, we describe an in situ LC-MS analytical probe, the Falcon probe, which integrates multiple functions of high-pressure sample injection without sample loss, high-efficiency LC separation, and electrospray. The main body of the Falcon probe is made of stainless steel and fabricated by the computer numerical control (CNC) technique, which has ultrahigh mechanical strength. By coupling a nanoliter-scale droplet reactor made of polyether ether ketone (PEEK) material, the Falcon probe-based LC-MS system was capable of operating at mobile-phase pressures up to 800 bar, which is comparable to those of conventional ultraperformance liquid chromatography (UPLC) systems. Using the probe pressing microamount in situ (PPMI) injection approach, the Falcon probe-based LC-MS system showed high separation efficiency and good repeatability with relative standard deviations (RSDs) of retention time and peak area of 1.8% and 9.9%, respectively, in peptide mixture analysis (n = 6). We applied this system to the analysis of a trace amount of 200 pg of HeLa protein digest and successfully identified an average of 766 protein groups (n = 5). By combining in situ sample pretreatment at the nanoliter range, we further applied the present system in single-cell proteomic analysis, and 241 protein groups were identified in single 293 cells, which preliminarily demonstrated its potential in the analysis of trace amounts of samples with complex compositions.

Banana MaNAC1 activates secondary cell wall cellulose biosynthesis to enhance chilling resistance in fruit.

Chilling injury has a negative impact on the quantity and quality of crops, especially subtropical and tropical plants. The plant cell wall is not only the main source of biomass production, but also the first barrier to various stresses. Therefore, improving the understanding of the alterations in cell wall architecture is of great significance for both biomass production and stress adaptation. Herein, we demonstrated that the cell wall principal component cellulose accumulated during chilling stress, which was caused by the activation of MaCESA proteins. The sequence-multiple comparisons show that a cold-inducible NAC transcriptional factor MaNAC1, a homologue of Secondary Wall NAC transcription factors, has high sequence similarity with Arabidopsis SND3. An increase in cell wall thickness and cellulosic glucan content was observed in MaNAC1-overexpressing Arabidopsis lines, indicating that MaNAC1 participates in cellulose biosynthesis. Over-expression of MaNAC1 in Arabidopsis mutant snd3 restored the defective secondary growth of thinner cell walls and increased cellulosic glucan content. Furthermore, the activation of MaCESA7 and MaCESA6B cellulose biosynthesis genes can be directly induced by MaNAC1 through binding to SNBE motifs within their promoters, leading to enhanced cellulose content during low-temperature stress. Ultimately, tomato fruit showed greater cold resistance in MaNAC1 overexpression lines with thickened cell walls and increased cellulosic glucan content. Our findings revealed that MaNAC1 performs a vital role as a positive modulator in modulating cell wall cellulose metabolism within banana fruit under chilling stress.

Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Injectable hydrogel encapsulating siMMP13 with anti-ROS and anti-apoptotic functions for osteoarthritis treatment.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential. RESULTS: In this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers. CONCLUSION: In summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

Pharmacokinetics and pharmacodynamic evaluation of hyaluronic acid-modified imatinib-loaded PEGylated liposomes in CD44-positive Gist882 tumor-bearing mice.

To develop a PEGylated and CD44-targeted liposomes, enabled by surface coating with hyaluronic acid (HA) via amide bond to improve the efficacy of imatinib mesylate (IM), for tumor-targeted cytoplasmic drug delivery. HA was covalently grafted on DSPE-PEG2000-NH2 polymer. HA-modified or unmodified PEGylated liposomes were prepared with ethanol injection method, and the stability, drug release, and cytotoxicity of these liposomes were studied. Meanwhile, intracellular drug delivery efficiency, antitumor efficacy, and pharmacokinetics were also investigated. Ex vivo fluorescence biodistribution was also detected by small animal imaging. In addition, endocytosis mechanism was also explored HA-coated PEGylated liposomes (137.5 nm ± 10.24) had a negative zeta potential (-29.3 mV ± 5.44) and high drug loading (27.8%, w/w). The liposomes were stable with cumulative drug leakage (<60%) under physiological conditions. Blank liposomes were nontoxic to Gist882 cells, and IM-loaded liposomes had higher cytotoxicity to Gist882 cells. HA-modified PEGylated liposomes were internalized more effectively than non-HA coating via CD44-mediated endocytosis. Besides, the cellular uptake of HA-modified liposomes also partly depends on caveolin-medicated endocytosis and micropinocytosis. In rats, both liposomes produced a prolonged half-life of IM (HA/Lp/IM: 14.97h; Lp/IM: 11.15h) by 3- to 4.5-folds compared with the IM solution (3.61h). HA-decorated PEGylated liposomes encapsulated IM exhibited strong inhibitory effect on tumor growth in Gist882 cell-bearing nude mice and formation of 2D/3D tumor spheroids. The Ki67 immunohistochemistry result was consistent with the above results. IM-loaded PEGylated liposomes modified with HA exerted the excellent anti-tumor effect on tumor-bearing mice and more drugs accumulated into the tumor site.

A Novel Quercetin Encapsulated Glucose Modified Liposome and Its Brain-Target Antioxidative Neuroprotection Effects.

Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU-Glu-Lip), aiming not only to overcome QU's poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU-Glu-Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116-124 nm), small PDI value (<0.3), zeta value -1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood-brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU-Glu-Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU-Glu-Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU-Glu-Lip application for more effective treatment of NDDs.

Prevalence and risk factors of dental fluorosis among children aged 8-12 years in Shandong province of China.

This study was to investigate the prevalence and severity of children's dental fluorosis (DF) in Shandong and identified the potential risk factors for DF. A total of 87 villages in Shandong were investigated to calculate the prevalence of DF and Community Fluorosis Index (CFI) in 2018-2019. Six hundred and seventy children were enrolled to identify the potential risk factors using univariate and multivariate logistic regressions. Goodman-Kruskal Gamma was used to explore the factors related to the severity of DF. In 87 villages, 1249 of 8700 (14.36%) children still have DF. The prevalence of DF in most villages was below 40% in 2018-2019. Water fluorine concentration when selected for the study and urinary fluorine concentration were related to the risk of DF (P < 0.001). Some eating habits, like lower frequency of eating fresh vegetables, eggs, and beans, were associated with the risk of DF (P < 0.001). The high water fluorine concentration, and lower frequency of eating fresh vegetables, eggs, and beans were also related to the severity of DF (P < 0.001). DF in children in Shandong province is still a common endemic disease. This study tries to provide a useful guide for the prevention and control of DF.

Therapeutic effects of curcumin liposomes and nanocrystals on inflammatory osteolysis: In vitro and in vivo comparative study.

Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent than that of Cur-NCs, both in vitro and in vivo, although the cellular uptake of Cur-NCs was quicker. In conclusion, the results demonstrate that Cur-LPs have great potential for the clinical treatment of inflammatory osteolysis and that the therapeutic effect is closely related to the liposomal dosage form.

Photoresponsive Diarylethene-Containing Polymers: Recent Advances and Future Challenges.

Photoresponsive polymers have attracted increasing interest owing to their potential applications in anticounterfeiting, information encryption, adhesives, etc. Among them, diarylethene (DAE)-containing polymers are one of the most promising photoresponsive polymers and have unique thermal stability and fatigue resistance compared to azobenzene- and spiropyran-containing polymers. Herein, the design of DAE-containing polymers based on different types of structures, including main chain polymers, side-chain polymers, and crosslinked polymers, is introduced. The mechanism and applications of DAE-containing polymers in anti-counterfeiting, information encryption, light-controllable adhesives, and photoinduced healable materials are reviewed. In addition, the remaining challenges of DAE-containing polymers are also discussed.

Microcapsules and Nanoliposomes Based Strategies to Improve the Stability of Blueberry Anthocyanins.

Blueberry anthocyanins are water-soluble natural pigments that can be used as both natural antioxidants and natural colorants. However, their structural instability greatly limits their application in the food, pharmaceutical, and cosmetic industries. In this study, blueberry anthocyanin microcapsules (BAM) and blueberry anthocyanin liposomes (BAL) were fabricated based on blueberry anthocyanins. Film dispersion methods were used to prepare the BAL. Their preparation processes were optimized and compared to improve the stability of the blueberry anthocyanins following exposure to light and high temperatures. The BAM were prepared through complex phase emulsification. The blueberry anthocyanins were protected by the shell materials composed of sodium alginate after being formed into BAM. Under the optimal conditions, the embedding rate of BAM and BAL can reach as high as 96.14% and 81.26%, respectively. In addition, the particle size, zeta potential, microtopography, and structure feature information of the BAM and BAL were compared. The average particle sizes of the BAM and BAL were 9.78 µm and 290.2 nm, respectively, measured using a laser particle size analyzer, and the zeta potentials of the BAM and BAL were 34.46 mV and 43.0 mV, respectively. In addition, the optimal preparation processes were determined through single-factor and response surface optimization experiments. The most important factors in the single-factor experiment for the preparation of microcapsules and liposomes were the content of CaCl2 and the amount of anthocyanin. The preservation rates in the light and dark were also compared, and the thermal stabilities of the BAM and BAL were characterized through differential thermal scanning. The results showed that both the BAM and BAL maintained the stability of blueberry anthocyanins, and no significant difference was found between the indices used to evaluate their stability. The results of this study provide theoretical support for the development of effective systems to maintain the stability of anthocyanins, thereby improving their bioavailability after ingestion by humans.

Polyacetylene Isomers Isolated from Bidens pilosa L. Suppress the Metastasis of Gastric Cancer Cells by Inhibiting Wnt/ß-Catenin and Hippo/YAP Signaling Pathways.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, ß-catenin, GSK3ß, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/ß-catenin and Hippo/YAP signaling pathways.

Effects of different frequencies of Er:YAG laser on the bonding properties of zirconia ceramic.

The effects of Er:YAG laser with different frequencies on zirconia ceramic's bonding properties were studied. In total, 42 Y-TZP (yttrium-stabilized tetragonal zirconia polycrystals, UPCERA ST) with 3 mm × 3 mm × 2 mm divided into 6 groups (n = 7): control (C), sandblasting (SB), and Er:YAG laser (A1-A4), which the frequencies correspond to 5 Hz, 10 Hz, 15 Hz, and 20 Hz, IPS e.max Press ceramics were B. Scanning electron microscope (SEM) images were recorded. The ceramics were bonded to enamel from extracted teeth. After being constantly stored at 37 ℃ for 24 h, the shear test was performed with a universal testing machine. Stereomicroscope evaluated fracture modes. Stereomicroscope evaluated fracture modes. Data were analyzed by SPSS26.0 statistical software; the standard was P = 0.05. (1) The SEM showed the surface of A1-A4 became rough compared with C. (2) The shear test showed that the highest bonding strength for B was 13.15 ± 2.97 MPa, followed by SB was 7.78 ± 0.97 MPa, and A2 was 7.13 ± 0.75 MPa. However, there was no significant difference between SB and A2 (P > 0.05). Fracture modes of C were the interface fracture of Y-TZP and resin adhesive; most of A1-A4 and SB also were interface fracture, a few mixed fractures, and cohesion fracture of resin adhesive; B were all mixed fracture. Er:YAG laser with 10 Hz could be used as an alternative to sandblasting with Al2O3 for surface modification of Y-TZP to increase the bonding strength.

Airlift two-phase partitioning bioreactor for dichloromethane removal: Silicone rubber stimulated biodegradation and its auto-circulation.

Solid non-aqueous phases (NAPs), such as silicone rubber, have been used extensively to improve the removal of volatile organic compounds (VOCs). However, the removal of VOCs is difficult to be further improved because the poor understanding of the mass transfer and reaction processes. Further, the conventional reactors were either complicated or uneconomical. In view of this, herein, an airlift bioreactor with silicone rubber was designed and investigated for dichloromethane (DCM) treatment. The removal efficiency of Reactor 1 (with silicone rubber) was significantly higher than that of Reactor 2 (without silicone rubber), with corresponding higher chloride ion and CO2 production. It was found that Reactor 1 achieved a much better DCM shock tolerance capability and biomass stability than Reactor 2. Silicone rubber not only enhanced the mass transfer in terms of both gas/liquid and gas/microbial phases, but also decreased the toxicity of DCM to microorganisms. Noteworthily, despite the identical inoculum used, the relative abundance of potential DCM-degrading bacteria in Reactor 1 (91.2%) was much higher than that in Reactor 2 (24.3%) at 216 h. Additionally, the silicone rubber could be automatically circulated in the airlift bioreactor due to the driven effect of the airflow, resulting in a significant reduction of energy consumption.

CRISPR-/Cas12a-Mediated Liposome-Amplified Strategy for the Surface-Enhanced Raman Scattering and Naked-Eye Detection of Nucleic Acid and Application to Food Authenticity Screening.

Surface-enhanced Raman scattering (SERS) has been recognized as a powerful tool for biosensors due to the ultrahigh sensitivity and unique fingerprint information. However, there are some limitations in trace target nucleic acid detection for the restricted signal-transducing and amplification strategies. Inspired by CRISPR/Cas12a with specific target DNA-activated collateral single-strand DNA (ssDNA) cleavage activity and liposome with signal molecule-loading properties, we first proposed a sensitive SERS-based on-site nucleic acid detection strategy mediated by CRISPR/Cas12a with trans-cleavage activity on ssDNA linkers utilized to capture liposomes. Liposomes loading two kinds of signal molecules, 4-nitrothiophenol (4-NTP) and cysteine, could achieve the dual-mode detection of target DNA with SERS and naked eye, respectively. The promptly amplified signals were initiated by the triggered breakdown of signal molecule-loaded liposomes. Emancipated 4-NTP, a biological-silent Raman reporter, would achieve highly selective and sensitive SERS measurement. Released cysteine induced the aggregation of plasmonic gold nanoparticles, leading to an obvious red to blue colorimetric shift to realize portable naked-eye detection. With this strategy, target nucleic acid concentration was dexterously converted into SERS and visualization signals and could be detected as low as 100 aM and 10 pM, respectively. The approach was also successfully applied to determine meat adulteration, achieving the detection of a low adulteration ratio in the complicated food matrix. We anticipate that this strategy will not only be regarded as a universal platform for the on-site detection of food authenticity but also broaden SERS application for the accurate determination of diverse biomarkers.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

A Photopolymerized Semi-Interpenetrating Polymer Networks-Based Hydrogel Incorporated with Nanoparticle for Local Chemotherapy of Tumors.

PURPOSE: To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery. METHODS: Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method. RESULTS: The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice. CONCLUSIONS: This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.

Dietary shifts and diversities of individual life histories reveal cultural dynamics and interplay of millets and rice in the Chengdu Plain, China during the Late Neolithic (2500-2000 cal. BC).

OBJECTIVES: We undertook a more comprehensive analyses than our previous study (Yi et al., International Journal of Osteoarchaeology, 2018, 28, 636-644) at the Gaoshan site (~2500-2000 cal. BC) to expand our understanding of the different roles of rice and millets to human subsistence strategies, diachronic shift of human diets, diversity of human life histories and cultural influence (dental ablation) to human population. MATERIALS AND METHODS: Carbon and nitrogen isotopic analyses of human (ribs and long bones, n = 68) and animal (n = 15) bones as well as carbonized seeds from rice and millets (n = 8) were undertaken. Human bones were directly AMS-14 C dated. In addition, sequential sampling of 16 individuals with varied age and sex and cultural contexts for isotopic analysis was also conducted. RESULTS: The calibrated dating results (n = 27) indicate that there existed two periods of occupation at the site, ~2500-2200 BC and ~2200-1900 BC. Moderate high δ15 N values were found in the crops. Isotopic data from bone collagen suggest that the humans mainly relied on C3 -based animal protein and were supplemented by C4 -based foods. This isotopic pattern is also seen in pigs. Significant difference of human δ13 C values (Mann-Whitney U test, p < 0.05) between the two periods was observed. Compared to the bones, the isotopic data of human dentine serial sections show a much wider variability and higher δ13 C values. DISCUSSION: The crops (millets and rice) were probably manured. Human individuals subsisted on rice/millet agriculture and pigs in general. In combination with the radiocarbon dates, the increase of C3 (rice) consumption by the humans was found from the early (2500-2200 cal. BC) to late (2200-2000 cal. BC) periods, indicating the intensification of rice agriculture through time. However, four categories of human life histories during childhood are identified given different isotopic profiles of dentine sections, demonstrating that C3 (rice) and C4 (millets)-based foods played different roles in human lives. Even though, there were similar weaning practices among the human populations. It is surprising that human individuals with dental ablation, cultural characteristic in the Middle and Lower Yangtze River Valley, consumed more millets during childhood in the early period than those without dental ablation in the late period. Our study here provides novel insights into cultural dynamics and the interplay between rice and millets in rice-millet agricultural system during the Late Neolithic in Southwest China.