The effect and mechanism of variable particle size microplastics and levofloxacin on the neurotoxicity of Rana nigromaculata based on the microorganism-intestine-brain axis.

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants in combination with other environmental pollutants, such as levofloxacin (LVFX). After a 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, LVFX was neurotoxic to Rana nigromaculata tadpoles. The order of the effects of the exposure treatment on tadpole behavior was: LVFX-MP3>LVFX-MP1>LVFX-MP2 ≥ LVFX. Results of transcriptome analysis of tadpole brain tissue showed that LVFX in combination with 0.10 and 10.00 µm MP interferes with the nervous system through the cell adhesion molecules pathway. Interestingly, the order of effects of the co-exposure on oxidative stress in the intestine was inconsistent with that of tadpole behavior. We found that Paraacteroides might be a microplastic indicator species for the gut microbiota of aquatic organisms. The results of the targeted metabolism of neurotransmitters in the intestine suggest that in the LVFX-MP2 treatment, LVFX alleviated the intestinal microbiota disorder caused by 1.00 µm MP, by regulating intestinal microbiota participating in the TCA cycle VI and gluconeogenesis and tetrapyrrole biosynthesis I, while downregulating Met and Orn, and upregulating 5HIAA, thereby easing the neurotoxicity to tadpoles exposed to LVFX-MP2. This work is of great significance for the comprehensive assessment of the aquatic ecological risks of microplastics-antibiotic compound pollutants.

Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans.

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.

The Xyloglucan Endotransglucosylase/Hydrolase Gene XTH22/TCH4 Regulates Plant Growth by Disrupting the Cell Wall Homeostasis in Arabidopsis under Boron Deficiency.

TCH4 is a xyloglucan endotransglucosylase/hydrolase (XTH) family member. Extensive studies have shown that XTHs are very important in cell wall homeostasis for plant growth and development. Boron (B), as an essential micronutrient for plants, plays an essential role in the cross-linking of cell wall pectin. However, the effect of B on cell wall organization is unclear. This study aimed to explore the mechanism of plant adaption to B stress by investigating the role of TCH4 in cell wall homeostasis. We conducted both plate and hydroponic cultures of wild-type Col-0 and overexpression and gene knockout lines of XTH22/TCH4 to analyze the phenotype, components, and characteristics of the cell wall using immunofluorescence, atomic force microscopy (AFM), and transmission electron microscopy (TEM). B deficiency induces the expression of TCH4. The overexpression lines of TCH4 presented more sensitivity to B deficiency than the wild-type Col-0, while the knockout lines of TCH4 were more resistant to low B stress. Up-regulation of TCH4 influenced the ratio of chelator-soluble pectin to alkali-soluble pectin and decreased the degree of methylesterification of pectin under B-deficient conditions. Moreover, we found that B deficiency disturbed the arrangement of cellulose, enlarged the gap between cellulose microfibrils, and decreased the mechanical strength of the cell wall, leading to the formation of a thickened and deformed triangular region of the cell wall. These symptoms were more profound in the TCH4 overexpression lines. Consistently, compared with Col-0, the O2- and MDA contents in the TCH4 overexpression lines increased under B-deficient conditions. This study identified the B-deficiency-induced TCH4 gene, which regulates cell wall homeostasis to influence plant growth under B-deficient conditions.

Phosphorylated/Nonphosphorylated Motifs in Amelotin Turn Off/On the Acidic Amorphous Calcium Phosphate-to-Apatite Phase Transformation.

Amelotin (AMTN) as a matrix protein exerts a direct effect on biomineralization by modulating apatite (HAP) formation during the dental enamel maturation stage through the specific interaction of a potentially phosphorylated Ser-Ser-Glu-Glu-Leu (SSEEL) peptide fragment with calcium phosphate (Ca-P) surfaces. However, the roles of (non)phosphorylation of this evolutionarily conserved subdomain within AMTN remain poorly understood. Here, we show, by time-resolved atomic force microscopy (AFM) imaging of in situ HAP crystallization via the HPO42--rich amorphous calcium phosphate (acidic ACP), the on/off switching of the phase transformation process through a nonphosphorylation-to-phosphorylation transition of the SSEEL motif. Using high-resolution transmission electron microscopy (HRTEM), we observed that the acidic ACP phase is stabilized by the phosphorylated SSEEL motif, delaying its transformation to HAP, whereas the nonphosphorylated counterpart promotes HAP formation by accelerating the dissolution-recrystallization of the acidic ACP substrate. Dynamic force spectroscopy measurements demonstrate greater binding energies of nonphosphorylated SSEEL to the acidic ACP substrate by the formation of molecular peptide-ACP bonding, explaining the enhanced dissolution of the acidic ACP substrate by stronger complexion with surface Ca2+ ions. Our findings demonstrate direct evidence for the switching role of (non)phosphorylation of an evolutionarily conserved subdomain within AMTN in controlling the phase transition of growing enamel and designing tissue regeneration biomaterials.

A General Strategy for Ligand Exchange on Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles with a suitable surface coating are appealing for biomedical applications. Because high-quality upconversion nanoparticles are typically prepared in an organic solvent and passivated by hydrophobic oleate ligands, a convenient and reliable method for the surface modification of upconversion nanoparticles is thus highly desired to satisfy downstream biological investigations. In this work, we describe a facile and versatile strategy for displacing native oleate ligands on upconversion nanoparticles with a diversity of hydrophilic molecules. The ligand-exchange procedure involves the removal of original oleate ligands followed by the attachment of new ligands in a separate step. The successful coating of relevant ligands was confirmed by Fourier transform infrared spectroscopy, thermogravimetry analysis, and ζ-potential measurement. The surface-modified nanoparticles display high stability and good biocompatibility, as revealed by electron microscopy, photoluminescence spectroscopy, and cytotoxicity assessment. Our study demonstrates that functional biomolecules such as biotin can be directly immobilized on the nanoparticle surface using this approach for the quick and effective detection of streptavidin.

Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells.

Recently, numerous types of human dental tissue-derived mesenchymal stem cells (MSCs) have been isolated and characterized, including dental pulp stem cells, stem cells from exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor cells, alveolar bone-derived MSCs, stem cells from apical papilla, tooth germ progenitor cells, and gingival MSCs. All these MSC-like cells exhibit self-renewal, multilineage differentiation potential, and immunomodulatory properties. Several studies have demonstrated the potential advantages of dental stem cell-based approaches for regenerative treatments and immunotherapies. This review outlines the properties of various dental MSC-like populations and the progress toward their use in regenerative therapy. Several dental stem cell banks worldwide are also introduced, with a view toward future clinical application.

Controlled surface chemistry of diamond/ß-SiC composite films for preferential protein adsorption.

Diamond and SiC both process extraordinary biocompatible, electronic, and chemical properties. A combination of diamond and SiC may lead to highly stable materials, e.g., for implants or biosensors with excellent sensing properties. Here we report on the controllable surface chemistry of diamond/ß-SiC composite films and its effect on protein adsorption. For systematic and high-throughput investigations, novel diamond/ß-SiC composite films with gradient composition have been synthesized using the hot filament chemical vapor deposition (HFCVD) technique. As revealed by scanning electron microscopy (SEM), the diamond/ß-SiC ratio of the composite films shows a continuous change from pure diamond to ß-SiC over a length of ∼ 10 mm on the surface. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to unveil the surface termination of chemically oxidized and hydrogen treated surfaces. The surface chemistry of the composite films was found to depend on diamond/ß-SiC ratio and the surface treatment. As observed by confocal fluorescence microscopy, albumin and fibrinogen were preferentially adsorbed from buffer: after surface oxidation, the proteins preferred to adsorb on diamond rather than on ß-SiC, resulting in an increasing amount of proteins adsorbed to the gradient surfaces with increasing diamond/ß-SiC ratio. By contrast, for hydrogen-treated surfaces, the proteins preferentially adsorbed on ß-SiC, leading to a decreasing amount of albumin adsorbed on the gradient surfaces with increasing diamond/ß-SiC ratio. The mechanism of preferential protein adsorption is discussed by considering the hydrogen bonding of the water self-association network to OH-terminated surfaces and the change of the polar surface energy component, which was determined according to the van Oss method. These results suggest that the diamond/ß-SiC gradient film can be a promising material for biomedical applications which require good biocompatibility and selective adsorption of proteins and cells to direct cell migration.

Engineered probiotic overcomes pathogen defences using signal interference and antibiotic production to treat infection in mice.

Probiotic supplements are suggested to promote human health by preventing pathogen colonization. However, the mechanistic bases for their efficacy in vivo are largely uncharacterized. Here using metabolomics and bacterial genetics, we show that the human oral probiotic Streptococcus salivarius K12 (SAL) produces salivabactin, an antibiotic that effectively inhibits pathogenic Streptococcus pyogenes (GAS) in vitro and in mice. However, prophylactic dosing with SAL enhanced GAS colonization in mice and ex vivo in human saliva. We showed that, on co-colonization, GAS responds to a SAL intercellular peptide signal that controls SAL salivabactin production. GAS produces a secreted protease, SpeB, that targets SAL-derived salivaricins and enhances GAS survival. Using this knowledge, we re-engineered probiotic SAL to prevent signal eavesdropping by GAS and potentiate SAL antimicrobials. This engineered probiotic demonstrated superior efficacy in preventing GAS colonization in vivo. Our findings show that knowledge of interspecies interactions can identify antibiotic- and probiotic-based strategies to combat infection.

Synthesis and photophysical properties of polyfluorene with dipicolylamine groups on the side chain: highly selective and sensitive detection of histidine.

Two new polyfluorenes with dipicolylamine (DPA) pendant, PF-TDPA and PF-HDPA, are designed and synthesized by pre- and post-functionalization, respectively. PF-TDPA with a rigid side chain shows a selective fluorescence quenching upon the addition of Cu(2+) in a mixture solution of tetrahydrofuran and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. What is more, the PF-TDPA/Cu(2+) complex can selectively detect histidine over other amino acids with a fluorescence recovery. In contrast, PF-HDPA with a flexible spacer exhibits a fluorescence quenching to Cu(2+) but slightly fluorescence recovery after the addition of histidine. This indicates that the proper distance between the two DPA groups play an important role in the detection of histidine.

New water-soluble cationic poly(p-phenylenevinylene) derivative: the interaction with DNA and selective fluorescence enhancement induced by ssDNA.

A new cationic cyano-substituted poly(p-phenylenevinylene) (N-CNPPV) is synthesized by Knoevenagel condensation. The water-soluble polymer shows different emission spectra in different solvents and displays unique fluorescent behaviors in the mixed solvents of water and THF. The new polymer can form a complex with ssDNA by adopting a more planar conformation, exhibiting red shift of emission wavelength and enhancement of fluorescence intensity. By investigating the fluorescent response of N-CNPPV to various surfactants, we demonstrate that the hydrophobic interaction and electrostatic interaction result in the selective response of N-CNPPV to ssDNA. This is the first report on selective fluorescence enhancement of conjugated polyelectrolyte induced by ssDNA.

Polymer-Rich Dense Phase Can Concentrate Metastable Silica Precursors and Regulate Their Mineralization.

Multistep mineralization processes are pivotal in the fabrication of functional materials and are often characterized by far from equilibrium conditions and high supersaturation. Interestingly, such 'nonclassical' mineralization pathways are widespread in biological systems, even though concentrating molecules well beyond their saturation level is incompatible with cellular homeostasis. Here, we show how polymer phase separation can facilitate bioinspired silica formation by passively concentrating the inorganic building blocks within the polymer dense phase. The high affinity of the dense phase to mobile silica precursors generates a diffusive flux against the concentration gradient, similar to dynamic equilibrium, and the resulting high supersaturation leads to precipitation of insoluble silica. Manipulating the chemistry of the dense phase allows to control the delicate interplay between polymer chemistry and silica precipitation. These results connect two phase transition phenomena, mineralization and coacervation, and offer a framework to achieve better control of mineral formation.

Organosilicon and inorganic silica inhibit polystyrene nanoparticles uptake in rice.

Nanoplastics (NPs) have become an emerging global environmental problem, and the toxicity of polystyrene nanoplastics (PS-NPs) in rice plants has received widespread attention. However, few studies have focused on silicon (Si)-mediated interactions between PS-NPs and rice. Thus, two forms of Si (organosilicon/inorganic silica) treated rice cells were exposure of positively or negatively charged NPs, PS-NH2 and PS-COOH, to evaluate the effects of Si for defense against PS-NPs toxicity in rice. The result showed PS-NH2 nanoparticles were accumulated at relatively low levels in cells compared with that of PS-COOH, but induced a higher accumulation of hydrogen peroxide (H2O2) and superoxide radicals (O2•-). However, both organosilicon and inorganic silica can generate more negative potential on the surfaces of cell wall to absorb large numbers of positively charged PS-NH2. In addition, they can prevent the uptake of both PS-NH2 and PS-COOH through reducing the porosity on the surface of the cell walls. These finally alleviated the toxicity of oxidative stress caused by PS-NPs and improved the viability of rice cells. Our findings demonstrated the significant contribution of Si in combating PS-NPs in rice.

Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury.

Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1ß into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1ß when liver reinjury occurs. In light of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.

Chitosan biomaterial enhances the effect of OECs on the inhibition of sciatic nerve injury-induced neuropathic pain.

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.

Copolythiophene-derived colorimetric and fluorometric sensor for visually supersensitive determination of lipopolysaccharide.

3-Phenylthiophene-based water-soluble copolythiophenes (CPT1) were designed for colorimetric and fluorometric detection of lipopolysaccharide (LPS). The sensor (CPT1-C) shows a high selectivity to LPS in the presence of other negatively charged bioanalytes as well an extreme sensitivity with the detection limit at picomolar level, which is the lowest ever achieved among all synthetic LPS sensors available thus far. Significantly, the sensing interaction can be apparently observed by the naked eyes, which presents a great advantage for its practical applications. The appealing performance of sensor was demonstrated to originate from the multiple electrostatic and hydrophobic cooperative interactions, synergetic with signal amplification via the conformational change of the 3-phenylthiophene-based copolymer main chain. As a straightforward application, CPT1-C is capable of rapidly discriminating the Gram-negative bacteria (with LPS in the membrane) from Gram-positive bacteria (without LPS).

In Situ Observation of Dicalcium Phosphate Monohydrate Formation and Phase Transformation.

Calcium orthophosphates (CaPs), as important minerals in biomineralization and biomedicine, have attracted wide attention. Dicalcium phosphate monohydrate (DCPM, CaHPO4·H2O), the recently discovered crystalline CaP phase, has a higher metastability than dihydrate (DCPD, CaHPO4·2H2O) and anhydrate (DCPA, CaHPO4), which may lead to many potential applications in functional biomaterial development. However, the preparation of large-sized DCPM and the underlying mechanisms of its formation and phase evolution remain unclear. Herein, for the first time, we propose a method to prepare micrometer-sized DCPM under an acidic water-methanol mixture and using in situ time-resolved atomic force microscopy further explore its crystallization via dissolution of an acidic amorphous calcium phosphate. In support of the potential role of DCPM as the biomaterial, we demonstrate that DCPM can quickly evolve into more stable octacalcium phosphate in a near-physiological solution. This work provides a mechanistic understanding of the formation and phase transformation of DCPM, which may serve as a basis for subsequent synthesis and application of DCPM as functional biomaterials.

How Microalgae is Effective in Oxygen Deficiency Aggravated Diseases? A Comprehensive Review of Literature.

Hypoxia can aggravate the conditions of many oxygen-deficiency-aggravated diseases (ODAD), such as cancer, ischemic heart disease, and chronic wounds. Photosynthetic microalgae can alleviate the hepatotoxicity of the local microenvironment by producing oxygen. In addition, microalgae extracts have antitumor, anti-inflammatory, antibacterial, and antioxidant effects. These properties make them attractive candidates for developing methods to treat ODAD. Although researchers have exploited the advantages of microalgae and developed a variety of microalgae-based biomaterials to treat ODAD, a comprehensive review of this topic has not been presented previously. Therefore, in this review, we summarize the development and progress made in the field of developing microalgae-based biomaterials toward the treatment of ODAD. The challenges and prospects of this field are also discussed.

Isolation and Identification of Adipose Stem Cell Exosomes and the Study of Its Potential as Drug Delivery Carrier In Vitro.

Most small molecule anticancer drugs have high lipophilicity and low water solubility, which is often regarded as a key obstacle to their development and clinical applications. A variety of nano-size drug carriers, like liposomes, has been developed for solubilizing these drugs. Naturally secreted by cells, exosomes have good biocompatibility and are considered as "natural liposomes." Exosomes released by mesenchymal stem cells (MSCs) not only have the properties like the ones generated by other cells but may also possess many therapeutic bioactive factors uniquely secreted by stem cells. In the present study, exosomes secreted by murine adipose stem cells (mASCs) were isolated, identified, and characterized. Its potential as drug delivery carrier and its biological effects on hepatoma cells and normal liver cell lines were explored in vitro. The data indicated that mASC exosomes separated by our improved sequential filtration method have particle size distribution in 30-150 nm, positively expresses TSG101, CD63, CD9, GADPH, and negatively expresses calnexin. The exosomes of mASCs obtained by this method could be taken up by cells and inhibit the cell activity of hepatoma cells HepG2, while enhance the normal cell activity of THLE-2. The results suggest that ASC exosomes are ideal potential drug delivery carriers and have the prospect of applications in carcinoma treatments.

A novel hypocrellin-based assembly for sonodynamic therapy against glioblastoma.

The non-invasive treatment of glioblastoma (GBM) is of great significance and can greatly reduce the complications of craniotomy. Sonodynamic therapy (SDT) is an emerging tumor therapeutic strategy that overcomes some fatal flaws of photodynamic therapy (PDT). Different from PDT, SDT has deep tissue penetration and can be applied in the non-invasive treatment of deep-seated tumors. However, effective sonosensitizers that can be used for SDT of GBM are still very rare. Herein, we have prepared a suitable assembly based on a hypocrellin derivative (CTHB) with good biocompatibility. Excitedly, the hypocrellin-based assembly (CTHB NPs) can effectively produce reactive oxygen species under ultrasound stimulation. The inherent fluorescence and photoacoustic imaging characteristics of the CTHB NPs are conducive to the precise positioning of the tumors. It has been proved both in subcutaneous and in intracranial tumor models that CTHB NPs can be used as an effective sonosensitizer to inhibit tumor growth under ultrasound irradiation. This hypocrellin-based assembly has a good clinical prospect in the non-invasive treatment of GBM.

Soft-hard hybrid covalent-network polymer sponges with super resilience, recoverable energy dissipation and fatigue resistance under large deformation.

Energy absorption or dissipation ability has been widely developed in tough hydrogels and 3D nano-structured sponges for a variety of applications. However, fully recoverable energy dissipation and fatigue resistance under large deformation is still challenging yet highly desirable. Polymer network with homogeneous chemical crosslinking structures is an efficient way to construct hydrogels with high resilience and fatigue resistance. Unfortunately, such polymer network usually has poor energy dissipation capability. In this paper, we propose a new approach to build the ability of fully recoverable energy dissipation into covalent-crosslink polymer network by integrating soft and hard chains in a uniform crosslinking network and present the one-pot synthesis method for constructing corresponding polymer sponges by low-temperature phase-separation photopolymerization. The application of such polymer sponges as a tissue engineering scaffold, fabricated by using cyclic acetal units and PEG based monomers in particular is demonstrated. For the first time, we show the feasibility of building a synthetic scaffold with the characteristics of high porosity, super compressibility and resilience, fast recovery, completely recoverable energy dissipation, high fatigue resistance, biodegradability and biocompatibility. Such a scaffold is promising in tissue engineering especially in load-bearing applications.