NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging.

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres.

Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.

Nano-drug delivery system with enhanced tumour penetration and layered anti-tumour efficacy.

The low delivery efficiency of nano-drugs and limited tumour penetration are still huge challenges in treating solid tumours. Herein, we developed a pH-responsive nano-drug delivery system, CALS/PDMA@DOX, with a size conversion-layered delivery function. The system is composed of a pH-responsive cationic liposome loaded with DOX (CALS) and a polyamidoamine dendrimer loaded with DOX (PAMAM@DOX) modified with 2,3-dimethylmaleic anhydride (PDMA@DOX) using electrostatic adsorption. In the tumour microenvironment, the positively-charged large-size CALS and the positively-charged small-size PAMAM@DOX were dissociated to exert anti-tumour effects. CALS preferentially targeted tumour angiogenesis endothelial cells. Because of its small size and positive charge, PAMAM@DOX showed excellent tumour penetration. Significant tumour suppression by the system in vivo was confirmed in a 4T1 tumour xenograft mouse model. This pH-triggered size-switching layered delivery nanosystem is a safe and effective cancer treatment delivery platform that improves drug permeability and therapeutic efficacy.

Pretreatment of Wheat Straw Lignocelluloses by Deep Eutectic Solvent for Lignin Extraction.

In order to increase the fractionation efficiency of the wheat straw, a deep eutectic solvent (DES) system consisting of chlorine/lactic acid was used in this study for wheat straw pretreatment. The outcomes exhibited that DES pretreatment significantly enhanced the capability to extract lignin, retain cellulose, and remove hemicellulose. The best condition for the pretreatment of wheat straw was 150 °C for 6 h. The process retained most cellulose in the pretreated biomass (49.94-73.60%), and the enzymatic digestibility of the pretreatment residue reached 89.98%. Further characterization of lignin showed that the high yield (81.54%) and the high purity (91.33%) resulted from the ether bond cleavage in lignin and the connection between hemicellulose and lignin. As for application, the enzymatic hydrolysis of the best condition reached 89.98%, and the lignin also had suitable stability. The investigation exhibited that DES pretreatment has the potential to realize an efficient fractionation of lignocellulosic biomass into high-applicability cellulose and lignin of high-quality.

Self-assembly of cholesterol end-capped polymer micelles for controlled drug delivery.

BACKGROUND: During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions. RESULTS: The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 × 10-4 to 4.33 × 10-4 mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution. CONCLUSIONS: The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.

Flame Retardancy and Thermal Behavior of an Unsaturated Polyester Modified with Kaolinite-Urea Intercalation Complexes.

Organic modified kaolinite-urea intercalation complex (KUIC) was prepared using dimethyl sulfoxide (DMSO) as the precursor of kaolinite intercalation. Its structure was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD). Subsequently, as a synergistic agent, KUIC was combined with flame retardant ammonium polyphosphate (APP) to improve the flame retardant and smoke suppression performance of unsaturated polyester (UP) resin. A cone calorimeter (CONE) was used to study its flame retardancy and smoke suppression, and a scanning electron microscope (SEM) and thermogravimetry (TG) were used to study the micro morphology of the char and flame retardant mechanism. The results show that 12 phr of APP and 3 phr of KUIC were doped into UP to obtain a 28.0% limiting oxygen index (LOI) value. Compared with UP, the heat release rate and smoke production of UP/APP/KUIC composites were greatly decreased. Meanwhile, KUIC indeed enhanced the mechanical properties of UP.

The Pros1/Tyro3 axis protects against periodontitis by modulating STAT/SOCS signalling.

Periodontitis, an oral inflammatory disease caused by periodontal pathogen infection, is the most prevalent chronic inflammatory disease and a major burden on healthcare. The TAM receptor tyrosine kinases (Tyro3, Axl and Mertk) and their ligands (Gas6 and Pros1) play a pivotal role in the resolution of inflammation and have been associated with chronic inflammatory and autoimmune diseases. In this study, we evaluated the effects of exogenous Pros1 in in vitro and in vivo models of periodontitis. We detected higher Pros1 but lower Tyro3 levels in inflamed gingival specimens of periodontitis patients compared with healthy controls. Moreover, Pros1 was mostly localized in the gingival epithelium of all specimens. In cultured human gingival epithelial cells (hGECs), Porphyromonas gingivalis LPS (p.g-LPS) stimulation down-regulated Pros1 and Tyro3. Exogenous Pros1 inhibited p.g-LPS-induced production of TNF-α, IL-6, IL-1ß, MMP9/2 and RANKL in a Tyro3-dependent manner as revealed by PCR, Western blot analysis, ELISA and gelatin zymography. Pros1 also restored Tyro3 expression down-regulated by p.g-LPS in hGECs. In rats treated with ligature and p.g-LPS, administration of Pros1 attenuated periodontitis-associated gingival inflammation and alveolar bone loss. Our mechanistic studies implicated SOCS1/3 and STAT1/3 as mediators of the in vitro and in vivo anti-inflammatory effects of Pros1. Collectively, the findings from this work supported Pros1 as a novel anti-inflammatory therapy for periodontitis.

Preliminary investigation on cytotoxicity of fluorinated polymer nanoparticles.

As well-known persistent organic pollutants (POPs), organofluorine pollutants such as perfluorooctane sulfonate (PFOS) have been proven to be bioaccumulated and harmful to health. However, toxicological assessment of organofluorinated nanoparticles, which have emerged as a novel tool for biomedical and industrial applications, is lacking, to the best of our knowledge. To assess the biological effects and health risk of fluorinated nanoparticles, trifluoroethyl aryl ether-based fluorinated poly(methyl methacrylate) nanoparticles (PTFE-PMMA NPs) were synthesized with various fluorine contents (PTFE-PMMA-1 NPs 12.0wt.%, PTFE-PMMA-2 NPs 6.1wt.% and PTFE-PMMA-3 NPs 5.0wt.%), and their cytotoxicity was investigated in this study. The in vitro experimental results indicated that the cytotoxicity of PTFE-PMMA NPs was mild, and was closely related to their fluorine (F) contents and F-containing side chains. Specifically, the cytotoxicity of PTFE-PMMA NPs decreased with increasing F content and F-containing side chains. After exposure to PTFE-PMMA NPs at a sublethal dose (50µg/mL) for 24hr, the phospholipid bilayer was damaged, accompanied by increasing permeability of the cell membrane. Meanwhile, the intracellular accumulation of reactive oxygen species (ROS) occurred, resulting in the increase of DNA damage, cell cycle arrest and cell death. Overall, the PTFE-PMMA NPs were found to be relatively safe compared with typical engineered nanomaterials (ENMs), such as silver nanoparticles and graphene oxide, for biomedical and industrial applications.

Amide bond-containing monodisperse polyethylene glycols beyond 10 000 Da.

Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10 262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model.

Polydopamine-embedded Cu(2-x)Se nanoparticles as a sensitive biosensing platform through the coupling of nanometal surface energy transfer and photo-induced electron transfer.

Full understanding and easy construction of specific biosensing principles is necessary for disease diagnostics and therapeutics in the hope of creating new types of biosensors. Herein, we developed a new conceptual nanobiosensing platform by coupling nanometal surface energy transfer (NSET) and photo-induced electron transfer (PET) with polydopamine-embedded Cu(2-x)Se nanoparticles (Cu(2-x)SeNPs@pDA) and DNA-conjugated fluorescent organic dyes. The new prepared Cu(2-x)SeNPs@pDA has intense and broad localized surface plasmon resonance (LSPR) absorption over UV to near infrared (NIR) wavelengths, with different affinities toward ssDNA versus dsDNA. It also exhibits a high multiplexed fluorescence quenching ability, and thus can act as an acceptor in the energy transfer and electron transfer interactions between Cu(2-x)SeNPs@pDA and fluorescent organic dyes. As a proof of concept, a new biosensing platform has been successfully developed to target biomacromolecules such as DNA and proteins, in which the NSET and PET interactions between Cu(2-x)SeNPs@pDA and three different DNA-conjugated fluorescent dyes have been identified using steady-state and time-resolved fluorescence. A simple mathematical model was further applied to simulate the respective contributions of the coexisting NSET and PET to the total quenching observed for each DNA-conjugated dye in this sensing system. This study highlights the importance of understanding the mechanistic details of NSET and PET coupling processes, and the disclosed coupling mechanism of NSET and PET (NSET©PET) in the systems of Cu(2-x)SeNPs@pDA with wide wavelength range dyes provides new opportunities for sensitive biosensing applications.

[Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles].

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

Effect of biodrying of lignocellulosic biomass on humification and microbial diversity.

By optimizing the carbon to nitrogen (C/N) ratio, this study accomplished an improved level of humification and microbial diversity in the biodrying process of lignocellulosic biomass. The results demonstrated that C/N ratio of 20 accelerated the decomposition of refractory lignocellulose, resulting in lower greenhouse gas emissions and the production of highly mature fertilizer with a germination index of 119.0% and a humic index of 3.2. Moreover, C/N ratio of 20 was found to diversify microbial communities, including Pseudogracilibacillus, Sinibacillus, and Georgenia, which contributed to the decomposition of lignocellulosic biomass and the production of humic acid. Hence, it is recommended to regulate the C/N ratio to 20:1 during the biodrying of biogas residue and wood chips to promote the economic feasibility and bioresource recycling.

Preparation of microcrystalline cellulose from agricultural residues and their application as polylactic acid/microcrystalline cellulose composite films for the preservation of Lanzhou lily.

Microcrystalline celluloses were isolated from four agricultural residues, including sweet sorghum stalk, Jerusalem artichoke stalk, grains stillage, and Chinese herb residue, and characterized in terms of physicochemical and structural properties. The obtained microcrystalline celluloses were composited with polylactic acid as a packing film for the preservation of Lanzhou lily. All the agricultural residues-derived microcrystalline celluloses were in cellulose Iß structure with high purity and good thermal stability. Microcrystalline celluloses from sweet sorghum stalk had a higher degree of polymerization (327) and crystallinity (70.52 %) than others. The preservation effect of lily bulbs packaged by films were significantly improved indicated by the lessened weight loss rate and the meliorative hardness and whiteness, which ascribe to the repressed oxidation reactions. Polylactic acid/microcrystalline cellulose composite films prepared from sweet sorghum straw have been proved the most effective. This work could offer a value-added outlet for agricultural residues to produce microcrystalline celluloses-based biocompatible films for preservation of Lanzhou lily.

Diagnosis of Parkinson's Disease via the Metabolic Fingerprint in Saliva by Deep Learning.

Parkinson's disease (PD) is the second cause of the neurodegenerative disorder, affecting over 6 million people worldwide. The World Health Organization estimated that population aging will cause global PD prevalence to double in the coming 30 years. Optimal management of PD shall start at diagnosis and requires both a timely and accurate method. Conventional PD diagnosis needs observations and clinical signs assessment, which are time-consuming and low-throughput. A lack of body fluid diagnostic biomarkers for PD has been a significant challenge, although substantial progress has been made in genetic and imaging marker development. Herein, a platform that noninvasively collects saliva metabolic fingerprinting (SMF) by nanoparticle-enhanced laser desorption-ionization mass spectrometry with high-reproducibility and high-throughput, using ultra-small sample volume (down to 10 nL), is developed. Further, excellent diagnostic performance is achieved with an area-under-the-curve of 0.8496 (95% CI: 0.7393-0.8625) by constructing deep learning model from 312 participants. In conclusion, an alternative solution is provided for the molecular diagnostics of PD with SMF and metabolic biomarker screening for therapeutic intervention.

Improving lactic acid yield of hemicellulose from garden garbage through pretreatment of a high solid loading coupled with semi-hydrolysis using low enzyme loading.

Byproduct (acetate and ethanol) generation and carbon catabolite repression are two critical impediments to lactic acid production from the hemicellulose of lignocellulosic biomass. To reduce byproduct generations, acid pretreatment with high solid loading (solid-liquid ratio 1:7) of garden garbage was conducted. The byproduct yield was only 0.30 g/g during in the subsequent lactic acid fermentation from acid pretreatment liquid and 40.8% lower than that of low solid loading (0.48 g/g). Furthermore, semi-hydrolysis with low enzyme loading (10 FPU/g garden garbage cellulase) was conducted to regulate and reduce glucose concentration in the hydrolysate, thereby relieving carbon catabolite repression. During the lactic acid fermentation process, the xylose conversion rate was restored from 48.2% (glucose-oriented hydrolysis) to 85.7%, eventually achieving a 0.49 g/g lactic acid yield of hemicellulose. Additionally, RNA-seq revealed that semi-hydrolysis with low enzyme loading down-regulated the expression of ptsH and ccpA, thereby relieving carbon catabolite repression.

Surgical treatment of osteoporotic thoracolumbar compressive fractures with open vertebral cement augmentation of expandable pedicle screw fixation: a biomechanical study and a 2-year follow-up of 20 patients.

BACKGROUND: The incidence of screw loosening increases significantly in elderly patients with severe osteoporosis. Open vertebral cement augmentation of expandable pedicle screw fixation may improve fixation strength in the osteoporotic vertebrae. MATERIALS AND METHODS: Twenty cadaveric vertebrae (L1-L5) were harvested from six osteoporotic lumbar spines. Axial pullout tests were performed to compare the maximum pullout strength (Fmax) of four methods: 1. Conventional pedicle screws (CPS), 2. Expandable pedicle screws (EPS), 3. Cement augmentation of CPS (cemented-CPS), 4. Cement augmentation of EPS (cemented-EPS). Thirty-six consecutive patients with single-vertebral osteoporotic compressive fractures received posterior decompression and spinal fusion with cemented-CPS (16 cases) or cemented-EPS (20 cases). Plain film and/or CT scan were conducted to evaluate the spinal fusion and fixation effectiveness. RESULTS: The Fmax and energy absorption of cemented-EPS were significantly greater than three control groups. The mean BMD in the severe osteoporosis group was significantly lower than that in the osteoporosis group (t = 2.04, P = 0.036). In the osteoporosis group, cemented-EPS improved the Fmax by 43% and 21% over CPS and cemented-CPS group. In the severe osteoporosis group, cemented-EPS increased the Fmax by 59%, 22%, and 26% over CPS, EPS, and cemented-CPS, respectively. The clinical results showed that all patients suffered from severe osteoporosis. Six months after operation, the JOA and VAS scores in cemented-EPS group improved from 11.4 ± 2.6 and 7.0 ± 1.4 mm to 24.9 ± 1.6 and 2.1 ± 1.3 mm, respectively. No screw loosening occurred in the cemented-EPS group and spinal fusion was achieved. In the cemented-CPS group, four screws loosened (4.2%) according to the radiolucency. Six months after operation, the JOA and VAS scores improved from 13.1 ± 1.9 and 7.6 ± 1.5 mm to 22.8 ± 2.2 and 2.5 ± 1.6 mm, respectively. No cement leaked into the spinal canal in both groups. CONCLUSIONS: Cemented-EPS could increase fixation strength biomechanically. It could reduce the risks of screw loosening in patients with severe osteoporosis, requiring instrumented arthrodesis.

Diagnosis and treatment of ectopic thyroid carcinoma: A case report and literature review.

Introduction: Ectopic thyroid cancer (ETC) is primary thyroid cancer occurring in ectopic thyroid tissue, and its incidence rate is approximately 0.3%-0.5% of thyroid cancer. Only approximately 132 cases of ETC have been diagnosed and treated worldwide in the past 110 years, with most of them being adults. Of note, patients with ETC are prone to misdiagnosis and mistreatment. Case report: This was a 13-year-old adolescent female who reported having a sensation of swallowing obstruction when eating blocky foods. Color Doppler Ultrasound (CDU) found a 2.3 cm ×1.7 cm × 2.1 cm hypoechoic nodule slightly to the right of the deep surface of the tongue base, with a honeycomb shape. Meanwhile, a mixed echogenic nodule of approximately 2.0 cm × 1.9 cm × 2.3 cm was seen deep in the mouth floor, and a very low echogenic region of 1.4 cm × 1.1 cm × 1.8 cm was observed in the nodule. We then performed a fine needle aspiration biopsy (FNAB) of the thyroid nodules guided by CDU, and the results showed papillary thyroid carcinoma (PTC). Then, a local extended resection of the thyroid carcinoma was performed. Bilateral cervical IA and adjacent subhyoid lymph node dissection was performed through a small anterior cervical incision. The patient recovered well, and was discharged on the fifth day after surgery. The patient only took levothyroxine tablets for replacement therapy after surgery. The patient was followed up for 36 months, and the thyroid function remained in the normal range. Reexamination by CDU showed no tumor recurrence, lymph node enlargement, or obvious change in the tongue base ectopic thyroid. Conclusions: ETC is an extremely rare type of thyroid cancer, which is easy to be misdiagnosed. Preoperative use of CDU, nuclide scanning, computed tomography (CT)/Magnetic resonance imaging (MRI), and FNAB can significantly reduce the misdiagnosis rate of this disease. Surgery is currently the main treatment for ETC. Complete resection still has a high cure rate. For patients with advanced ETC who cannot be completely resected, external radiotherapy and targeted therapy can be tried, but the prognosis needs to be verified with more cases in the future.

Photo-crosslinkable methacrylated konjac glucomannan (KGMMA) hydrogels as a promising bioink for 3D bioprinting.

Three-dimensional (3D) bioink with favorable printability, strength, and biocompatibility challenged the 3D bioprinting technology in cartilage tissue engineering. Herein, we innovatively fabricated photo-crosslinkable methacrylated konjac glucomannan (KGMMA) as a novel biomaterial ink for 3D extrusion bioprinting in an attempt to construct precisely patterned tissues. Specifically, konjac glucomannan (KGM) was modified by methacrylic anhydride, which is a kind of photoreactive group, to form KGMMA. After UV crosslinking, the printed KGMMA hydrogel formed a covalent crosslinking network with high strength, desired shearing, and swelling and degradation characteristics. The properties of the KGMMA hydrogel could be modulated by changing the contents of MA. The shear-thinning property of the KGMMA biomaterial ink enables excellent printability, which can print different shapes including lattices, hexagons, and flowers. Furthermore, the bioinks support cell growth after being printed with chondrocytes for a culture. Therefore, the biodegradable, injectable, and photo-crosslinkable KGMMA biomaterial ink holds a great promise for cartilage tissue engineering.

Polystyrene microplastics increase estrogenic effects of 17α-ethynylestradiol on male marine medaka (Oryzias melastigma).

Microplastics (MPs) and endocrine disrupting chemicals are ubiquitous pollutants in marine environments, but their combined ecological risk is unclear. This study exposed male marine medaka (Oryzias melastigma) to 10 ng/L 17α-ethynylestradiol (EE2) alone or EE2 plus 2, 20, and 200 µg/L polystyrene MPs for 28 days to investigate the impacts of MPs on the reproductive disruption of EE2. The results showed that 10 ng/L EE2 alone did not affect biometric parameters, while co-exposure to EE2 and 20, 200 µg/L MPs suppressed the growth and decreased gonadosomatic and hepatosomatic indices. Compared to EE2 alone, EE2 plus MPs exposure significantly increased plasma 17ß-estradiol (E2) levels in a dose-dependent manner, and co-exposure to EE2 and 20, 200 µg/L MPs significantly increased the ratios of E2/testosterone (T). Moreover, EE2 plus MPs exposure elevated the transcription levels of estrogen biomarker genes vitellogenin and choriogenin, and estrogen receptor (ERα and ERß). Morphological analysis also showed that co-exposure to EE2 and MPs induced more severe damage to the testes and livers, indicating that MPs increased the toxicity of EE2. The actual EE2 concentrations in the solution increased with the exposure concentrations of MPs, suggesting that MPs changed the fate and behavior of EE2 in the seawater. These findings demonstrate that MPs could increase the estrogenic effects of EE2 on marine fish, suggesting that the combined health risk of MPs and endocrine disrupting chemicals on marine organisms should be paid great attention.