O-PRESS: Boosting OCT axial resolution with Prior guidance, Recurrence, and Equivariant Self-Supervision.

Optical coherence tomography (OCT) is a noninvasive technology that enables real-time imaging of tissue microanatomies. The axial resolution of OCT is intrinsically constrained by the spectral bandwidth of the employed light source while maintaining a fixed center wavelength for a specific application. Physically extending this bandwidth faces strong limitations and requires a substantial cost. We present a novel computational approach, called as O-PRESS, for boosting the axial resolution of OCT with Prior guidance, a Recurrent mechanism, and Equivariant Self-Supervision. Diverging from conventional deconvolution methods that rely on physical models or data-driven techniques, our method seamlessly integrates OCT modeling and deep learning, enabling us to achieve real-time axial-resolution enhancement exclusively from measurements without a need for paired images. Our approach solves two primary tasks of resolution enhancement and noise reduction with one treatment. Both tasks are executed in a self-supervised manner, with equivariance imaging and free space priors guiding their respective processes. Experimental evaluations, encompassing both quantitative metrics and visual assessments, consistently verify the efficacy and superiority of our approach, which exhibits performance on par with fully supervised methods. Importantly, the robustness of our model is affirmed, showcasing its dual capability to enhance axial resolution while concurrently improving the signal-to-noise ratio.

Electrically conductive coatings in tissue engineering.

Recent interest in tissue engineering (TE) has focused on electrically conductive biomaterials. This has been inspired by the characteristics of the cells' microenvironment where signalling is supported by electrical stimulation. Numerous studies have demonstrated the positive influence of electrical stimulation on cell excitation to proliferate, differentiate, and deposit extracellular matrix. Even without external electrical stimulation, research shows that electrically active scaffolds can improve tissue regeneration capacity. Tissues like bone, muscle, and neural contain electrically excitable cells that respond to electrical cues provided by implanted biomaterials. To introduce an electrical pathway, TE scaffolds can incorporate conductive polymers, metallic nanoparticles, and ceramic nanostructures. However, these materials often do not meet implantation criteria, such as maintaining mechanical durability and degradation characteristics, making them unsuitable as scaffold matrices. Instead, depositing conductive layers on TE scaffolds has shown promise as an efficient alternative to creating electrically conductive structures. A stratified scaffold with an electroactive surface synergistically excites the cells through active top-pathway, with/without electrical stimulation, providing an ideal matrix for cell growth, proliferation, and tissue deposition. Additionally, these conductive coatings can be enriched with bioactive or pharmaceutical components to enhance the scaffold's biomedical performance. This review covers recent developments in electrically active biomedical coatings for TE. The physicochemical and biological properties of conductive coating materials, including polymers (polypyrrole, polyaniline and PEDOT:PSS), metallic nanoparticles (gold, silver) and inorganic (ceramic) particles (carbon nanotubes, graphene-based materials and Mxenes) are examined. Each section explores the conductive coatings' deposition techniques, deposition parameters, conductivity ranges, deposit morphology, cell responses, and toxicity levels in detail. Furthermore, the applications of these conductive layers, primarily in bone, muscle, and neural TE are considered, and findings from in vitro and in vivo investigations are presented. STATEMENT OF SIGNIFICANCE: Tissue engineering (TE) scaffolds are crucial for human tissue replacement and acceleration of healing. Neural, muscle, bone, and skin tissues have electrically excitable cells, and their regeneration can be enhanced by electrically conductive scaffolds. However, standalone conductive materials often fall short for TE applications. An effective approach involves coating scaffolds with a conductive layer, finely tuning surface properties while leveraging the scaffold's innate biological and physical support. Further enhancement is achieved by modifying the conductive layer with pharmaceutical components. This review explores the under-reviewed topic of conductive coatings in tissue engineering, introducing conductive biomaterial coatings and analyzing their biological interactions. It provides insights into enhancing scaffold functionality for tissue regeneration, bridging a critical gap in current literature.

An in-depth review of the function of RNA-binding protein FXR1 in neurodevelopment.

FMR1 autosomal homolog 1 (FXR1) is an RNA-binding protein that belongs to the Fragile X-related protein (FXR) family. FXR1 is critical for development, as its loss of function is intolerant in humans and results in neonatal death in mice. Although FXR1 is expressed widely including the brain, functional studies on FXR1 have been mostly performed in cancer cells. Limited studies have demonstrated the importance of FXR1 in the brain. In this review, we will focus on the roles of FXR1 in brain development and pathogenesis of brain disorders. We will summarize the current knowledge in FXR1 in the context of neural biology, including structural features, isoform diversity and nomenclature, expression patterns, post-translational modifications, regulatory mechanisms, and molecular functions. Overall, FXR1 emerges as an important regulator of RNA metabolism in the brain, with strong implications in neurodevelopmental and psychiatric disorders.

Lower concentration polyethylene microplastics can influence free-floating macrophyte interactions by combined effects of many weak interactions: A nonnegligible ecological impact.

Microplastics (MPs) are ubiquitous in freshwater ecosystems and their accumulation has been considered an emerging threat. Early research on the effects of MPs on macrophytes primarily focused on the toxicological impacts on individual macrophytes, with several studies suggesting that lower concentrations of MPs have little impact on macrophytes. However, the ecological implications of lower MP concentrations on macrophyte communities remain largely unexplored. Here, we experimented to assess the effects of lower concentrations including 25 mg/L, 50 mg/L, 75 mg/L, and 100 mg/L of polyethylene (PE) microplastics on Spirodela polyrhiza and Lemna minor, and their community. Our results also indicated that PE concentrations below 100 mg/L had no significant effect on relative growth rate, specific leaf area, Chlorophyll a, Chlorophyll b, Chlorophyll a + b, carotenoid, malondialdehyde (MDA), catalase, and soluble sugar of monocultural S. polyrhiza. However, a lower concentration of PE significantly decreased the MDA of monocultural L. minor and significantly affected the comprehensive index of S. polyrhiza. These findings suggested that lower concentrations of PE can influence interactions between macrophytes maybe due to the cumulative effects of many weak interactions. Additionally, our study showed that 75 mg/L and 100 mg/L PE additions decreased the competitive balance index value of two macrophytes under mixed-culture condition. This result implied that the ecological influence of lower concentration MPs on macrophytes may manifest at the community level rather than at the population level, due to species-specific responses and varying degrees of sensitivity of macrophytes to PE concentrations. Thus, our study emphasizes the need to closely monitor the ecological consequences of emerging contaminants such as MPs accumulation on macrophyte communities, rather than focusing solely on the morphology and physiology of individual macrophytes.

From wings to whiskers to stem cells: why every model matters in fragile X syndrome research.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps.

Sol-gel derived B2O3-CaO borate bioactive glasses with hemostatic, antibacterial and pro-angiogenic activities.

Sol-gel borate bioactive glasses (BGs) are promising ion-releasing biomaterials for wound healing applications. Here, we report the synthesis of a series of binary B2O3-CaO borate BGs (CaO ranging from 50 to 90 mol%) using a sol-gel-based method. The influence of CaO content in B2O3-CaO borate BG on morphology, structure and ion release behavior was investigated in detail. Reduced dissolution (ion release) and crystallization could be observed in borate BGs when CaO content increased, while the morphology was not significantly altered by increasing CaO content. Our results evidenced that the ion release behavior of borate BGs could be tailored by tuning the B2O3/CaO molar ratio. We also evaluated the in vitro cytotoxicity, hemostatic, antibacterial and angiogenic activities of borate BGs. Cytocompatibility was validated for all borate BGs. However, borate BGs exhibited composition-dependent hemostatic, antibacterial and angiogenic activities. Generally, higher contents of Ca in borate BGs facilitated hemostatic activity, while higher contents of B2O3 were beneficial for pro-angiogenic activity. The synthesized sol-gel-derived borate BGs are promising materials for developing advanced wound healing dressings, given their fast ion release behavior and favorable hemostatic, antibacterial and angiogenic activities.

Extracellular and intracellular effects of bioactive glass nanoparticles on osteogenic differentiation of bone marrow mesenchymal stem cells and bone regeneration in zebrafish osteoporosis model.

Bioactive glass nanoparticles (BGNs) are well-recognized multifunctional biomaterials for bone tissue regeneration due to their capability to stimulate various cellular processes through released biologically active ions. Understanding the correlation between BGN composition and cellular responses is key to developing clinically usable BGN-based medical devices. This study investigated the influence of CaO content of binary SiO2-CaO BGNs (CaO ranging from 0 to 10 mol%) on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo bone regeneration in zebrafish osteoporosis model. The results showed that BGNs could promote osteogenic differentiation of rBMSCs by indirectly releasing active ions or directly interacting with rBMSCs by internalization. In both situations, BGNs of a higher CaO content could promote the osteogenic differentiation of rBMSCs to a greater extent. The internalized BGNs could activate the transcription factors RUNX2 and OSX, leading to the expression of osteogenesis-related genes. The results in the zebrafish osteoporosis model indicated that the presence of BGNs of higher CaO contents could enhance bone regeneration and rescue dexamethasone-induced osteoporosis to a greater extent. These findings demonstrate that BGNs can stimulate osteogenic differentiation of rBMSCs by releasing active ions or internalization. A higher CaO content facilitates osteogenesis and bone regeneration of zebrafish as well as relieving dexamethasone-induced osteoporosis. The zebrafish osteoporosis model can be a potent tool for evaluating the in vivo bone regeneration effects of bioactive materials. STATEMENT OF SIGNIFICANCE: Bioactive glass nanoparticles (BGNs) are increasingly used as fillers of nanocomposites or as delivery platforms of active ions to regenerate bone tissue. Various studies have shown that BGNs can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by releasing active ions. However, the correlation between BGN composition and cellular responses and in vivo bone regeneration effect has still not been well investigated. Establishment of a suitable in vivo animal model for investigating this correlation is also challenging. The present study reports the influence of CaO content in binary SiO2-CaO BGNs on osteogenic differentiation of BMSCs extracellularly and intracellularly. This study also demonstrates the suitability of zebrafish osteoporosis model to investigate in vivo bone regeneration effect of BGNs.

Surface engineering of mesoporous bioactive glass nanoparticles with bacteriophages for enhanced antibacterial activity.

Binary SiO2-CaO mesoporous bioactive glass nanoparticles (MBGNs) are multifunctional biomaterials able to promote osteogenic, angiogenic, and immunomodulatory activities. MBGNs have been applied in a variety of tissue regeneration strategies. However, MBGNs lack strong antibacterial activity and current strategies (loading of antibacterial ions or antibiotics) toward enhanced antibacterial activity may cause cytotoxicity or antibiotic resistance. Here we engineered MBGNs using bacteriophages (phages) to enhance the antibacterial activity. Salmonella Typhimurium (S. T) phage PFPV25.1 that can infect Salmonella enterica serovar Typhimurium strain LT2 was used as a model phage to engineer MBGNs. MBGNs were first modified with amine groups to enhance the affinity between phages and MBGNs surfaces. Afterward, the physicochemical and antibacterial activity of phage-engineered MBGNs was evaluated. The results showed that S. T phage PFPV25.1 was successfully bound onto MBGNs surfaces without losing their bioactivity. A higher quantity of phages could be bounded onto amine-functionalized MBGNs than onto non-functionalized MBGNs. Phages on amine-functionalized MBGNs exhibited higher antibacterial activity. The stability test showed that phages could remain on amine-functionalized MBGNs for over 28 days. This work provides valuable information on developing phage-modified MBGNs as a new and effective antibacterial system for biomedical applications.

Responses of submerged macrophytes to different particle size microplastics and tetracycline co-pollutants at the community and population level.

Microplastics (MPs) and antibiotics are ubiquitous in aquatic ecosystems, and their accumulation and combined effects are considered emerging threats that may affect biodiversity and ecosystem function. The particle size of microplastics plays an important role in their combined effects with antibiotics. Submerged macrophytes are crucial in maintaining the health and stability of freshwater ecosystems. However, little is known about the combined effects of different particle size of MPs and antibiotics on freshwater plants, particularly their effects on submerged macrophyte communities. Thus, there is an urgent need to study their effects on the macrophyte communities to provide essential information for freshwater ecosystem management. In the present study, a mesocosm experiment was conducted to explore the effects of three particle sizes (5 µm, 50 µm, and 500 µm) of polystyrene-microplastics (PSMPs) (75 mg/L), tetracycline (TC) (50 mg/L), and their co-pollutants on interactions between Hydrilla verticillata and Elodea nuttallii. Our results showed that the effects of MPs are size-dependent on macrophytes at the community level rather than at the population level, and that small and medium sized MPs can promote the growth of the two test macrophytes at the community level. In addition, macrophytes at the community level have a stronger resistance to pollutant stress than those at the population level. Combined exposure to MPs and TC co-pollutants induces species-specific responses and antagonistic toxic effects on the physio-biochemical traits of submerged macrophytes. Our study provides evidence that MPs and co-pollutants not only affect the morphology and physiology at the population level but also the interactions between macrophytes. Thus, there are promising indications on the potential consequences of MPs and co-pollutants on macrophyte community structure, which suggests that future studies should focus on the effects of microplastics and their co-pollutants on aquatic macrophytes at the community level rather than only at the population level. This will improve our understanding of the profound effects of co-pollutants in aquatic environments on the structure and behavior of aquatic communities and ecosystems.

Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development.

Fragile X messenger ribonucleoprotein 1 protein (FMRP) deficiency leads to fragile X syndrome (FXS), an autism spectrum disorder. The role of FMRP in prenatal human brain development remains unclear. Here, we show that FMRP is important for human and macaque prenatal brain development. Both FMRP-deficient neurons in human fetal cortical slices and FXS patient stem cell-derived neurons exhibit mitochondrial dysfunctions and hyperexcitability. Using multiomics analyses, we have identified both FMRP-bound mRNAs and FMRP-interacting proteins in human neurons and unveiled a previously unknown role of FMRP in regulating essential genes during human prenatal development. We demonstrate that FMRP interaction with CNOT1 maintains the levels of receptor for activated C kinase 1 (RACK1), a species-specific FMRP target. Genetic reduction of RACK1 leads to both mitochondrial dysfunctions and hyperexcitability, resembling FXS neurons. Finally, enhancing mitochondrial functions rescues deficits of FMRP-deficient cortical neurons during prenatal development, demonstrating targeting mitochondrial dysfunction as a potential treatment.

Mussel-Inspired Polydopamine Composite Mesoporous Bioactive Glass Nanoparticles: An Exploration of Potential Metal-Ion Loading Platform and In Vitro Bioactivity.

Exploring new approaches to realize the possibility of incorporating biologically active elements into mesoporous silicate bioactive glass nanoparticles (MBG NPs) and guaranteeing their meso- structural integrity and dimensional stability has become an attractive and interesting challenge in biomaterials science. We present a postgrafting strategy for introducing different metal elements into MBG NPs. This strategy is mediated by polydopamine (PDA) coating, achieving uniform loading of copper or copper-cobalt on the particles efficiently and ensuring the stability of MBG NPs in terms of particle size, mesoporous structure, and chemical structure. However, the PDA coating reduced the ion-binding free energy of the MBG NPs for calcium and phosphate ions, resulting in the deposition of minimal CaP clusters on the PDA@MBG NP surface when immersed for 7 days in simulated body fluid, indicating the absence of hydroxyapatite mineralization.

Double Optic Disc Pit With Retinal Pigmentation in a Woman With High Myopia.

This case report discusses a diagnosis of 2 optic disc pits in an otherwise asymptomatic woman with high myopia.

Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu.

Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to "remodel" the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating osteoblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the "barren" diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

Certificateless Public Auditing Scheme With Data Privacy and Dynamics in Group User Model of Cloud-Assisted Medical WSNs.

With the application of wireless sensor network (WSN) in healthcare field, online sharing of medical data has attracted more and more attention. However, wearable sensor nodes are limited in energy, storage space and data processing capacity, which largely restricts their deployment in resource demand application scenarios. Fortunately, cloud storage services can enrich the capabilities of wearable sensors and provide an effective method for people to share data within a group. However, as medical data directly relates to patients' health and privacy information, ensuring the integrity and privacy of medical records stored in cloud servers becomes a key issue to be urgently solved. Many public data auditing schemes have been put forward to address the above issues. Unfortunately, most of them have security vulnerabilities or poor functionality and performance. In this paper, we come up with a secure and efficient certificateless public auditing scheme for cloud-assisted medical WSNs, which not only supports dynamic data sharingand privacy protection, but also achieves efficient group user revocation. Security analysis and performance evaluation demonstrate that our scheme significantly reduce the total computation cost while achieving a higher security level. Compared with other related schemes, our new proposal is more suitable for group user data sharing in cloud-assisted medical WSNs.

Microplastics and co-pollutant with ciprofloxacin affect interactions between free-floating macrophytes.

Microplastic and antibiotic contamination are considered an increasing environmental problem in aquatic systems, while little is known about the impact of microplastics and co-pollutant with antibiotics on freshwater vascular plants, particularly the effects of interactions between macrophytes. Here, we performed a mesocosm experiment to evaluate the impact of polyethylene-microplastics and their co-pollutants with ciprofloxacin on the growth and physiological characteristics of Spirodela polyrhiza and Lemna minor and the interactions between these two macrophytes. Our results showed that microplastics alone cannot significantly influence fresh weight and specific leaf area of the two test free-floating macrophytes, but the effects on photosynthetic pigments, malondialdehyde, catalase and soluble sugar contents were species-specific. Ciprofloxacin can significant adverse effects on the growth and physiological traits of the two test macrophytes and microplastic mitigated the toxicity of ciprofloxacin on the two free-floating plants to a certain extent. In addition, our studies showed that microplastics and co-pollutants can influence relative yield and competitiveness of S. polyrhiza and L. minor by directly or indirectly influencing their physiology and growth. Therefore our findings suggest that species-specific sensibility to microplastic and its co-pollutant among free-floating macrophytes may influence macrophyte population dynamics and thereby community structure and ecosystem functioning. And microplastics altered other contaminant behaviours and toxicity, and may directly or indirectly influence macrophytes interactions and community structure. The present study is the first experimental study exploring the effects of microplastics alone and with their co-pollutants on interactions between free-floating macrophytes, which can provide basic theoretical guidance for improving the stability of freshwater ecosystems.

Complement 3a Mediates CCN2/CTGF in Human Retinal Pigment Epithelial Cells.

Background: Complement 3 (C3) is the crucial component of the complement cascade when retina was exposed to external stimulus. Cellular communication network 2/connective tissue growth factor (CCN2/CTGF) is important in response of retinal stress and a fulcrum for angiogenesis and fibrosis scar formation. Our study aims to explore the interaction between C3 and CCN2/CTGF via bioinformatics analyses and in vitro cell experiments. Methods: The GSE dataset was selected to analyse the chemokine expression in human retinal pigment epithelium (ARPE-19) cells under stimulus. Then, RPE cells were further transfected with or without C3 siRNA, followed by C3a (0.1 µM or 0.3 µM) for 24, 48, and 72 hours. Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure CCN2/CTGF mRNA and protein levels. Results: The GSE36331 revealed C3 expression was significantly elevated in RPE under stimulus. Compared with negative control, CCN2/CTGF mRNA was increased with all types of C3a treatments, whereas a significant increase of protein level was only observed with high concentration of 0.3 µM C3a for a prolonged 72-hour time. Compared with nontransfected cells, significant reductions of CCN2/CTGF mRNA were observed in the C3 siRNA transfected cells with 0.3 µM C3a for 24, 48, and 72 hours, and a significant reduction of CCN2/CTGF protein was observed with 0.3 µM C3a for 48 hours. Conclusions: C3 was elevated in RPE under environmental stimulus and long-term exposure to specified concentration of C3a increased CCN2/CTGF expression in RPE, which could be partially reversed by C3 siRNA.

Learning Two-Stream CNN for Multi-Modal Age-Related Macular Degeneration Categorization.

This paper tackles automated categorization of Age-related Macular Degeneration (AMD), a common macular disease among people over 50. Previous research efforts mainly focus on AMD categorization with a single-modal input, let it be a color fundus photograph (CFP) or an OCT B-scan image. By contrast, we consider AMD categorization given a multi-modal input, a direction that is clinically meaningful yet mostly unexplored. Contrary to the prior art that takes a traditional approach of feature extraction plus classifier training that cannot be jointly optimized, we opt for end-to-end multi-modal Convolutional Neural Networks (MM-CNN). Our MM-CNN is instantiated by a two-stream CNN, with spatially-invariant fusion to combine information from the CFP and OCT streams. In order to visually interpret the contribution of the individual modalities to the final prediction, we extend the class activation mapping (CAM) technique to the multi-modal scenario. For effective training of MM-CNN, we develop two data augmentation methods. One is GAN-based CFP/OCT image synthesis, with our novel use of CAMs as conditional input of a high-resolution image-to-image translation GAN. The other method is Loose Pairing, which pairs a CFP image and an OCT image on the basis of their classes instead of eye identities. Experiments on a clinical dataset consisting of 1,094 CFP images and 1,289 OCT images acquired from 1,093 distinct eyes show that the proposed solution obtains better F1 and Accuracy than multiple baselines for multi-modal AMD categorization. Code and data are available at https://github.com/li-xirong/mmc-amd.

Lactobacillus plantarum Lp3a improves functional constipation: evidence from a human randomized clinical trial and animal model.

Background: Functional constipation (FC) is a common gastrointestinal (GI) disorder characterized by symptoms of constipation without a clear physiologic or anatomic cause. Gut microbiome dysbiosis has been postulated to be a factor in the development of FC, and treatment with probiotic regimens, including strains of Lactobacillus plantarum (L. plantarum), has demonstrated efficacy in managing symptoms. To further understand the role of L. plantarum in GI health, we conducted an animal study and a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of a specific sub-strain, Lp3a, on FC. Methods: For the animal study, male Kunming mice were treated with doses of L. plantarum Lp3a ranging from 0.67 to 2.00 g/kg or an equivalent amount of placebo for 15 days prior to the induction of constipation via 20 mL/kg of 25% diphenoxylate solution. GI motility parameters including intestinal motion and stool amount were then assessed. In the human study, 120 patients with FC were randomized to treatment [L. plantarum Lp3a; 2×1.0×1010 (colony forming units; CFU) ×7 days] or control groups (n=60 each). The primary endpoint was survey information on FC signs/symptoms. Participants and observers were blinded to group allocation. A subset of 20 Lp3a treated patients underwent pre- and post-treatment 16 s ribosomal ribonucleic acid (rRNA) gene sequencing. Whole genome sequencing (WGS) of L. plantarum Lp3a was also performed. Results: Lp3a-treated mice showed significantly improved intestinal motion, reduced time to first defecation, and increased stool amounts. Similarly, patients in the treatment group (n=59) reported significant improvements in FC signs/symptoms compared to controls (n=58; all P<0.05). Although 16 s rRNA sequencing revealed no significant variations between pre- and post-treatment samples, WGS of Lp3a itself revealed several biological pathways that may underlie the relief of FC symptoms in animals and humans, including methane and fatty acid metabolism and bile acid biosynthesis. Conclusions: We found that the use of the novel probiotic sub-strain, L. plantarum Lp3a, led to clinically significant improvements in FC in both mice and humans, and identified the potential biological mechanisms underlying this activity.

Inactivation of Hedgehog signal transduction in adult astrocytes results in region-specific blood-brain barrier defects.

In this study, we use molecular genetic approaches to clarify the role of the Hedgehog (Hh) pathway in regulating the blood-brain/spinal cord barrier (BBB) in the adult mouse central nervous system (CNS). Our work confirms and extends prior studies to demonstrate that astrocytes are the predominant cell type in the adult CNS that transduce Hh signaling, revealed by the expression of Gli1, a target gene of the canonical pathway that is activated in cells receiving Hh, and other key pathway transduction components. Gli1+ (Hh-responsive) astrocytes are distributed in specific regions of the CNS parenchyma, including layers 4/5/6 of the neocortex, hypothalamus, thalamus, and spinal cord, among others. Notably, although BBB properties in endothelial cells are normally regulated by both paracellular and transcellular mechanisms, conditional inactivation of Hh signaling in astrocytes results in transient, region-specific BBB defects that affect transcytosis but not paracellular diffusion. These findings stand in contrast to prior studies that implicated astrocytes as a source of Sonic hedgehog that limited extravasation via both mechanisms [J. I. Alvarez et al., Science 334, 1727-1731 (2011)]. Furthermore, using three distinct Cre driver lines as well as pharmacological approaches to inactivate Hh-pathway transduction globally in CNS astrocytes, we find that these specific BBB defects are only detected in the rostral hypothalamus and spinal cord but not the cortex or other regions where Gli1+ astrocytes are found. Together, our data show that Gli1+ Hh-responsive astrocytes have regionally distinct molecular and functional properties and that the pathway is required to maintain BBB properties in specific regions of the adult mammalian CNS.

Fabrication of Submicro-Nano Structures on Polyetheretherketone Surface by Femtosecond Laser for Exciting Cellular Responses of MC3T3-E1 Cells/Gingival Epithelial Cells.

PURPOSE: Polyetheretherketone (PEEK) exhibits high mechanical strengths and outstanding biocompatibility but biological inertness that does not excite the cell responses and stimulate bone formation. The objective of this study was to construct submicro-nano structures on PEEK by femtosecond laser (FSL) for exciting the responses of MC3T3-E1 cells and gingival epithelial (GE) cells, which induce regeneration of bone/gingival tissues for long-term stability of dental implants. MATERIALS AND METHODS: In this study, submicro-nano structures were created on PEEK surface by FSL with power of 80 mW (80FPK) and 160 mW (160FPK). RESULTS: Compared with PEEK, both 80FPK and 160FPK with submicro-nano structures exhibited elevated surface performances (hydrophilicity, surface energy, roughness and protein absorption). Furthermore, in comparison with 80FPK, 160FPK further enhanced the surface performances. In addition, compared with PEEK, both 80FPK and 160FPK significantly excited not only the responses (adhesion, proliferation, alkaline phosphatase [ALP] activity and osteogenic gene expression) of MC3T3-E1 cells but also responses (adhesion as well as proliferation) of GE cells of human in vitro. Moreover, in comparison with 80FPK, 160FPK further enhanced the responses of MC3T3-E1 cells/GE cells. CONCLUSION: FSL created submicro-nano structures on PEEK with elevated surface performances, which played crucial roles in exciting the responses of MC3T3-E1 cells/GE cells. Consequently, 160FPK with elevated surface performances and outstanding cytocompatibility would have enormous potential as an implant for dental replacement.