Paleo-Geomorphology Determines Spatial Variability of Geogenic Ammonium Concentration in Quaternary Aquifers.

Naturally occurring (i.e., geogenic) ammonium in groundwater has been widely detected globally, but the major controls on its regional distribution have been poorly characterized. Here, we identified the dominant role of paleo-geomorphology driven by paleo-climate in controlling the spatial variability of geogenic ammonium in groundwater using random forest algorithm and revealed the underlying mechanisms based on borehole sediment analysis of data obtained from the Dongting Lake Plain of the central Yangtze River basins in China. In the paleo-channel (PC) area, the aquifer depth-matched sediments were deposited during the last deglaciation when warm climate resulted in rapid filling into incised valleys, and terrestrial organic matter (OM) mainly as lignin experienced less degradation prior to sedimentation and had lower humification, higher N abundance, and nominal oxidation state of carbon (NOSC). In the paleo-interfluve (PI) area, the depth-matched sediments were deposited during the last glaciation, followed by intensive erosion in the surface during the last glacial maximum, and terrestrial OM mainly as lignin had been partly degraded into aliphatics prior to sedimentation and had higher humification, lower N abundance, and NOSC. As a result, under the present anaerobic conditions, less-humic and N-rich OM with more oxidized C tends to be more intensively mineralized into ammonium in the PC area than those in the PI area. These findings highlight the importance of paleo-geomorphology with paleo-climate in controlling the enrichment of geogenic ammonium in groundwater, which has a universal significance for understanding the genesis and distribution of high N loads in the aquatic environment worldwide.

Transoral and submental endoscopic thyroidectomy (TOaST) for early stage papillary thyroid carcinoma: a real-world data retrospective cohort study.

INTRODUCTION: Although transoral endoscopic thyroidectomy (TOETVA) is widely utilized in clinical practice, some problems and restrictions still remain. Our study compared the perioperative features and early surgical efficacy of TOETVA and a modified transoral and submental endoscopic thyroidectomy (TOaST) in early stage papillary thyroid carcinoma (PTC). METHODS: The clinical data of PTC patients who underwent endoscopic thyroidectomy, including 42 modified TOaST patients and 114 traditional TOETVA patients, were retrospectively collected. Propensity score matching was employed to reduce patient selection bias. The perioperative features and early surgical efficacy data of two groups were compared. RESULTS: The operation time of the TOaST group was significantly shorter than that of the TOETVA group (150.00 ± 35.47 min vs. 168.75 ± 44.49 min; P = 0.030). Furthermore, the TOaST group required shorter days for a normal diet (3.38 ± 0.93 days vs. 4.04 ± 1.03 days; P = 0.000) and a shorter hospital stay than the TOETVA group (5.85 ± 2.17 days vs. 6.12 ± 2.01 days; P = 0.003). There was no statistical difference in complications between the two groups, but the probability of numbness of the lower lip and chin in the TOaST group was lower than that in the TOETVA group(5.12% vs. 13.04%, P = 0.321). The symptoms of mandibular numbness and hoarseness of most patients were relieved in both groups 6 months after surgery, and no abnormalities and recurrence were found in the thyroid ultrasound. All the patients were satisfied with the appearance of their surgical incision. CONCLUSION: In early stage PTC patients, TOaST had the same surgical effectiveness as traditional TOETVA but can minimize the probability of mandibular numbness and improve the perioperative quality of life.

Comparative evaluation of the volume of occlusal adjustment of repositioning occlusal devices designed by using an average value digital articulator and the jaw movement analyzer.

STATEMENT OF PROBLEM: The volume of occlusal adjustment of digital occlusal devices designed with different digital occlusal articulators is unknown. PURPOSE: The purpose of this clinical study was to evaluate and compare the clinical efficacy and volume of occlusal adjustment of digital occlusal devices designed by using an average value digital articulator and the jaw movement analyzer (JMA). MATERIAL AND METHODS: Thirty participants were randomly divided into 2 groups, an Average value group and a JMA group, with 15 participants in each group. The centric relation position of the participants was determined by an experienced investigator with the aid of a leaf gauge. An intraoral scanner (TRIOS 3) was used to obtain digital scans of the maxillary and mandibular dentition and the maxillomandibular relationship record in the centric relation position. Personalized articulator parameters of participants in the JMA group were obtained by using a JMA (JMAnalyser). Different articulator parameters were used to fabricate an occlusal device in a denture design software program (exocad DentalCAD). The surface of the occlusal device was coated with a dental optical spray and then scanned by using a laboratory scanner (Kavo LS3). The process was repeated after the occlusal device was adjusted. The files of the 2 scans were imported into a reverse engineering software program, and the root mean square (RMS) values were obtained by best-fit alignment and 3-dimensional comparison. The Shapiro-Wilk normality test and homogeneity of variance test were performed, and t tests were used to evaluate differences in the RMS values between the groups (α=.05). RESULTS: The experimental data were generally normally distributed (P>.05). No statistically significant difference was found between the RMS values of the Average and the JMA groups (P>.05). CONCLUSIONS: No significant difference in the volume of occlusal adjustment was found when using occlusal devices made by using the digital average articulator or the JMA, suggesting that either method can be used to program articulators for the fabrication of occlusal devices.

NIR-Light-Activated Ratiometric Fluorescent Hybrid Micelles for High Spatiotemporally Controlled Biological Imaging and Chemotherapy.

Intelligent-responsive imaging-therapy strategy has shown great significance for biomedicine. However, it is still a challenge to construct spatiotemporally controlled imaging-therapy systems triggered by near infrared (NIR) light. In this work, NIR-light-activated ratiometric fluorescent hybrid micelles (RFHM) are prepared via the co-assembly of upconversion nanoparticles (UCNPs), doxorubicin (DOX), and UV-light-responsive amphiphilic block copolymer for the spatiotemporally controlled imaging and chemotherapy. Upon NIR light irradiation, UCNPs can convert NIR light to UV light. The emitted UV light induces the photoreaction of copolymer to further trigger ratiometric fluorescence imaging and degradation of hybrid micelles, resulting in rapid DOX release from hybrid micelles for antitumor therapy. The animal experiments reveal that NIR light can not only remotely regulate the ratiometric fluorescence imaging of RFHM in tumor tissue, but also trigger DOX release from RFHM to inhibit tumor growth. Therefore, this study provides a new strategy to achieve high spatial-temporal-controlled biological imaging and chemotherapy.

Injectable Double Crosslinked Hydrogel-Polypropylene Composite Mesh for Repairing Full-Thickness Abdominal Wall Defects.

Abdominal wall defects are common clinical diseases, and mesh repair is the standard treatment method. The most commonly used polypropylene (PP) mesh in clinical practice has the advantages of good mechanical properties, stable performance, and effective tissue integration effect. However, direct contact between abdominal viscera and PP mesh can lead to severe abdominal adhesions. To prevent this, the development of a hydrogel-PP composite mesh with anti-adhesive properties may be an effective measure. Herein, biofunctional hydrogel loaded with rosmarinic acid is developed by modifying chitosan and Pluronic F127, which possesses suitable physical and chemical properties and commendable in vitro biocompatibility. In the repair of full-thickness abdominal wall defects in rats, hydrogels are injected onto the surface of PP mesh and applied to intraperitoneal repair. The results indicate that the use of hydrogel-PP composite mesh can alleviate abdominal adhesions resulting from traditional PP mesh implantation by decreasing local inflammatory response, reducing oxidative stress, and regulating the fibrinolytic system. Combined with the tissue integration ability of PP mesh, hydrogel-PP composite mesh has great potential for repairing full-thickness abdominal wall defects.

Micro-strain sensing using wrinkled stiff thin films on soft substrates as tunable optical grating.

We report a strain sensing approach that utilizes wrinkled patterns on poly (dimethylsiloxane) (PDMS) as an optical grating to measure thermally-induced strain of different materials. The mechanism for the strain sensing and the effect of PDMS grating on strain sensing are discussed. By bonding the PDMS grating onto a copper or silicon substrate, the coefficient of thermal expansion (CTE) of the substrates can be deduced by measuring the diffraction angle change due to the change in PDMS grating periodicity when thermal strain is introduced. The measured CTEs agree well with the known reference values.

Controlled morphology of thin film silicon integrated with environmentally responsive hydrogels.

Environmentally responsive hydrogels hold multiple important applications. However, the functionality of these materials alone is often limited in comparison to other materials like silicon; thus, there is a need to integrate soft and hard materials for the advancement of environmentally sensitive materials. Here we demonstrate the capability of integrating a thermoresponsive hydrogel, poly(N-isopropylacrylamide), with thin film silicon ribbons, enabling the stiff silicon ribbons to become adaptive and drivable by the soft environmentally sensitive substrate. This integration provides a means of mechanical buckling of the thin silicon film due to changes in environmental stimuli (e.g., temperature, pH). We also investigate how advanced lithographic techniques can be used to generate patterned deformation on the aforementioned integrated structures. Furthermore, we explore multilayer hybrid hydrogel structures formed by the integration of different types of hydrogels that have tunable curvatures under the influence of different stimuli. Silicon thin film integration on such tunable curvature substrates reveal characteristic reversible buckling of the thin film in the presence of multiple stimuli. These results open new opportunities for developing stretchable and intelligent devices for multiple applications.

Microplastics drive nitrification by enriching functional microorganisms in aquaculture pond waters.

The plastisphere refers to biofilm formation on the microplastic (MP) surface, but its subsequent functions, especially driving the nitrogen biogeochemical cycle, are rarely studied. Here, MPs were incubated in the pelagic water and benthic water-sediment interface of an aquaculture pond, and the two corresponding microcosms amended with incubated plastisphere were simulated. The results showed decreased ammonia concentrations and increased nitrification rates in microcosms with either pelagic or benthic plastispheres. To uncover the possible mechanisms, the community structure and function of the plastisphere were investigated. As clarified by 16S rRNA, the community diversity of the pelagic plastisphere was significantly higher than that of the corresponding hydrosphere. Plastisphere communities, especially those incubated in pelagic water, were separated from the hydrosphere. Moreover, the abundance of Proteobacteria increased while the abundance of Cyanobacteria decreased in both plastispheres. Metagenome further revealed that the abundance of amoA and annotated Nitrososphaeraceae_archaeon and hao and affiliated Nitrosomonas_europaea, which contributed to ammonia oxidation to nitrite, was higher in the benthic plastisphere. Comparing the pelagic plastisphere with the corresponding hydrosphere, however, the abundance of nxrA and annotated Nitrobacter hamburgensis and nxrB and the affiliated Nitrospira moscoviensis, which are involved in nitrite oxidation, was more abundant in the plastisphere. These findings suggest that the plastisphere might selectively enrich functional microorganisms and genes in a habitat-dependent manner to promote nitrification in aquaculture ponds.

Activation of the VpdmVGLUT1-VPM pathway contributes to anxiety-like behaviors induced by malocclusion.

Occlusal disharmony has a negative impact on emotion. The mesencephalic trigeminal nucleus (Vme) neurons are the primary afferent nuclei that convey proprioceptive information from proprioceptors and low-threshold mechanoreceptors in the periodontal ligament and jaw muscles in the cranio-oro-facial regions. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) and the ventral posteromedial nucleus (VPM) of thalamus have been proven to be crucial relay stations in ascending pathway of proprioception. The VPM sends numerous projections to primary somatosensory areas (SI), which modulate emotion processing. The present study aimed to demonstrate the ascending trigeminal-thalamic-cortex pathway which would mediate malocclusion-induced negative emotion. Unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was applied. Tract-tracing techniques were used to identify the existence of Vme-Vpdm-VPM pathway and Vpdm-VPM-SI pathway. Chemogenetic and optogenetic methods were taken to modulate the activation of VpdmVGLUT1 neurons and the Vpdm-VPM pathway. Morphological evidence indicated the involvement of the Vme-Vpdm-VPM pathway, Vpdm-VPM-SI pathway and VpdmVGLUT1-VPM pathway in orofacial proprioception in wild-type mice and vesicular glutamate transporter 1 (VGLUT1): tdTomato mice, respectively. Furthermore, chemogenetic inhibition of VpdmVGLUT1 neurons and the Vpdm-VPM pathway alleviated anxiety-like behaviors in a unilateral anterior crossbite (UAC) model, whereas chemogenetic activation induced anxiety-like behaviors in controls and did not aggravate these behaviors in UAC mice. Finally, optogenetic inhibition of the VpdmVGLUT1-VPM pathway in VGLUT1-IRES-Cre mice reversed UAC-induced anxiety comorbidity. In conclusion, these results suggest that the VpdmVGLUT1-VPM neural pathway participates in the modulation of malocclusion-induced anxiety comorbidity. These findings provide new insights into the links between occlusion and emotion and deepen our understanding of the impact of occlusal disharmony on brain dysfunction.

Sequential oxygen supply system promotes peripheral nerve regeneration by enhancing Schwann cells survival and angiogenesis.

Local hypoxia in cellular grafts remains a challenge during the repair of peripheral nerve injury. Oxygen carriers (perfluorotributylamine, PFTBA) have been shown to provide oxygen to Schwann cells (SCs) for a short period. However, the limited oxygen supply from oxygen-carrying materials hinders the ability of such systems to counteract hypoxia over an extended period and limits their therapeutic potential. In this study, PFTBA/VEGF core-shell fibers were fabricated through coaxial electrospinning to construct an oxygen supply system that can sequentially provide oxygen, first via the oxygen carrier and subsequently by promoting angiogenesis via VEGF. Then, the oxygen release and proangiogenic effects of the PFTBA/VEGF core-shell fibers were examined in vitro. Furthermore, sequential oxygen supply conduits prepared using the fibers and filled with SCs were used to bridge 15-mm-long sciatic nerve defects in rats. The PFTBA-VEGF system was confirmed to protect SCs from hypoxia and promote angiogenesis in vitro. Subsequent in vivo studies showed that after the oxygen carried by PFTBA was exhausted, the VEGF could induce neovascularization, and the nascent blood vessels acted as sequential oxygen suppliers for SCs during nerve regeneration. In addition, rats transplanted with the sequential oxygen supply system showed significant morphological and functional improvements in axonal regeneration, the sciatic function index, and the muscle wet weight ratio. The final functional outcomes were similar after treatment with the sequential oxygen supply conduits and autografts. Western blots revealed that the VEGF in the system could upregulate p-AMPK, contributing to axon regeneration after sciatic nerve injury. The sequential oxygen supply system offers essential insights into the oxygen regulation of biomaterials and highlights the potential of oxygen supply strategies as therapeutic approaches for repairing defects in peripheral nerves and other aerobic tissues.

Thermoresponsiveness of integrated ultra-thin silicon with poly(N-isopropylacrylamide) hydrogels.

Stimuli-sensitive polymer materials have limited device functionality, design and manufacturing flexibility although they are pushed to enable smart device applications. Here we demonstrate the capability of integrating thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with silicon nanoribbons, and enable the stiff silicon ribbons to become adaptive and drivable by the soft environmentally sensitive substrate, such as becoming mechanically stretched and compressed on temperature change. These and related soft/hard smart devices and systems may open new opportunities in biomedical applications.

TME-Responsive Polyprodrug Micelles for Multistage Delivery of Doxorubicin with Improved Cancer Therapeutic Efficacy in Rodents.

It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox-responsive polyprodrug composed of amphiphilic pH-sensitive diblock copolymer poly(ethylene glycol) methyl ether-b-poly(ß-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) is designed and developed. This polyprodrug can self-assemble into micelles (DOX-ss@PMs) at low concentration with high serum stability, indicating that DOX-ss@PMs have prolonged circulation time. The dual pH/redox-responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that DOX-ss@PMs can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage DOX-ss@PMs can more efficiently inhibit the growth of tumors and improve the survival of tumor-bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and DOX-ss@PMs could be a promising nanomedicine for cancer chemotherapy.

The meconium microbiota shares more features with the amniotic fluid microbiota than the maternal fecal and vaginal microbiota.

The early-life gut microbiota is associated with potential development of diseases in adulthood. The sterile womb paradigm has been challenged by recent reports that revealed the presence of the meconium, amniotic fluid, and placenta microbiome. This study aimed to explore the maternal origin of the microbiota of neonate meconium by using the PacBio single-molecule real-time circular consensus sequencing technology. Such technology could produce high fidelity reads of full-length 16S rRNA genes, improving the sensitivity and specificity of taxonomic profiling. It also reduced the risk of false positives. This study analyzed the full-length 16S rRNA-based microbiota of maternal samples (amniotic fluid, feces, vaginal fluid, saliva) and first-pass meconium of 39 maternal-neonate pairs. Alpha- and beta-diversity analyses revealed sample type-specific microbiota features. Most sample types were dominated by sequences representing different genera (Lactobacillus and Curvibacter in the amniotic fluid and vaginal fluid microbiota; Bacillus and Escherichia/Shigella in the meconium microbiota; Bacteroides and Faecalibacterium in the maternal fecal microbiota; Streptococcus and Prevotella in the maternal saliva microbiota). Moreover, specific operational taxonomic units (OTUs) were identified in all sample types. Dyad analysis revealed common OTUs between the meconium microbiota and microbiota of multiple maternal samples. The meconium microbiota shared more features with the amniotic fluid microbiota than the maternal fecal and vaginal microbiota. Our results strongly suggested that the meconium microbiota was seeded from multiple maternal body sites, and the amniotic fluid microbiota contributed most to the seeding of the meconium microbiota among the investigated maternal body sites.

Conjugating Micropatches to Living Cells Through Membrane Intercalation.

Existing clinical cell therapies, which rely on the use of biological functionalities of living cells, can be further enhanced by conjugating functional particles to the cells to form cell-particle complexes. Disk-shaped microparticles produced by the top-down microfabrication approach possess unique advantages for this application. However, none of the current mechanisms for conjugating the microfabricated microparticles to the cells are principally applicable to all types of cells with therapeutic potentials. On the other hand, membrane intercalation is a well-established mechanism for attaching fluorescent molecules to living cells or for immobilizing cells on a solid surface. This paper reports a study on conjugating disk-shaped microparticles, referred to as micropatches, to living cells through membrane intercalation for the first time. The procedure for producing the cell-micropatch complexes features an unprecedented integration of microcontact printing of micropatches, end-grafting of linear molecules of octadecyl chain and poly(ethylene glycol) to the printed micropatches, and use of gelatin as a temperature-sensitive sacrificial layer to allow the formation and subsequent release of the cell-micropatch complexes. Complexes composed of mouse neuroblastoma cells were found to be stable in vitro, and the micropatch-bound cells were viable, proliferative, and differentiable. Moreover, complexes composed of four other types of cells were produced. The membrane-intercalation mechanism and the corresponding fabrication technique developed in this study are potentially applicable to a wide range of therapeutic cells and thus promise to be useful for developing new cell therapies enhanced by the disk-shaped microparticles.

Magnetic Field Promotes Migration of Schwann Cells with Chondroitinase ABC (ChABC)-Loaded Superparamagnetic Nanoparticles Across Astrocyte Boundary in vitro.

PURPOSE: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. METHODS: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. RESULTS: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. CONCLUSION: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.

Flocculation-dewatering behavior of waste activated sludge particles under chemical conditioning with inorganic polymer flocculant: Effects of typical sludge properties.

The effects of typical sludge properties (solids concentration, soluble extracellular polymeric substances (SEPS) and alkalinity) on waste activated sludge flocculation-dewatering behavior and mechanisms under chemical conditioning with inorganic polymer flocculant-polyaluminum chloride (PACl) were systematically examined in this study. The results indicated that increasing the solids concentration was conductive to sludge dewatering and could greatly decrease the PACl demand in chemical conditioning. Solids concentration had important effects on properties of sludge floc flocculated with PACl, floc structure was more compact and of low EPS concentration at high solids concentrations. High levels of SEPS were adverse to sludge dewaterability after flocculation with PACl, since the SEPS could interact with hydroxy-aluminium through complexation and increase the demand of coagulants. In addition, advantageous speciations of hydroxy-aluminium were rapidly converted into amorphous hydroxides with low flocculation activity at high alkalinity, so the sludge conditioning efficiency was greatly declined. At the same time, the dominant mechanism of chemical conditioning was changed from charge neutralization to sweep coagulation. Finally, this study provides control strategies at complex sludge properties for improving the effectiveness of PACl as a chemical conditioner.

Chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel promote peripheral nerve regeneration in rats.

Treating peripheral nerve defects represents a clinical challenge, and nerve conduits lacking an internal scaffold lead to limited large nerve gap regeneration. Here, we bridged 10-mm sciatic nerve defects in rats with a chitosan conduit filled with 0, 0.5, or 1.0 mg of simvastatin in Pluronic F-127 hydrogel. We assessed subsequent nerve regeneration using the sciatic functional index (SFI), electrophysiological assessments, Fluoro-Gold (FG) retrograde tracing, gastrocnemius muscle mass measurements, and histological and immunohistochemical assessments of nerve regeneration. Ten weeks after implantation, the chitosan conduit filled with simvastatin/Pluronic F-127 hydrogel promoted nerve regeneration; there were significant increases in the SFI, compound muscle action potential peak amplitude, motor nerve conduction velocity, FG-labeled neuron number in the dorsal root ganglia, myelin sheath thickness, axon diameter, gastrocnemius wet weight, and muscle fiber area percentage in the gastrocnemius muscle (all p < 0.05). The expression levels of neurotrophic factors, such as pleiotrophin, hepatocyte growth factor, vascular endothelial growth factor, and glial cell line-derived neurotrophic factor, were also found to be increased. The results suggest that chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel improved peripheral nerve regeneration and functional recovery in rats, which may have been related to the increased expression of several endogenous neurotrophic factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 787-799, 2018.

A compound scaffold with uniform longitudinally oriented guidance cues and a porous sheath promotes peripheral nerve regeneration in vivo.

Scaffolds with inner fillers that convey directional guidance cues represent promising candidates for nerve repair. However, incorrect positioning or non-uniform distribution of intraluminal fillers might result in regeneration failure. In addition, proper porosity (to enhance nutrient and oxygen exchange but prevent fibroblast infiltration) and mechanical properties (to ensure fixation and to protect regenerating axons from compression) of the outer sheath are also highly important for constructing advanced nerve scaffolds. In this study, we constructed a compound scaffold using a stage-wise strategy, including directionally freezing orientated collagen-chitosan (O-CCH) filler, electrospinning poly(ε-caprolactone) (PCL) sheaths and assembling O-CCH/PCL scaffolds. Based on scanning electron microscopy (SEM) and mechanical tests, a blend of collagen/chitosan (1:1) was selected for filler fabrication, and a wall thickness of 400 µm was selected for PCL sheath production. SEM and three-dimensional (3D) reconstruction further revealed that the O-CCH filler exhibited a uniform, longitudinally oriented microstructure (over 85% of pores were 20-50 µm in diameter). The electrospun PCL porous sheath with pore sizes of 6.5 ±â€¯3.3 µm prevented fibroblast invasion. The PCL sheath exhibited comparable mechanical properties to commercially available nerve conduits, and the O-CCH filler showed a physiologically relevant substrate stiffness of 2.0 ±â€¯0.4 kPa. The differential degradation time of the filler and sheath allows the O-CCH/PCL scaffold to protect regenerating axons from compression stress while providing enough space for regenerating nerves. In vitro and in vivo studies indicated that the O-CCH/PCL scaffolds could promote axonal regeneration and Schwann cell migration. More importantly, functional results indicated that the CCH/PCL compound scaffold induced comparable functional recovery to that of the autograft group at the end of the study. Our findings demonstrated that the O-CCH/PCL scaffold with uniform longitudinal guidance filler and a porous sheath exhibits favorable properties for clinical use and promotes nerve regeneration and functional recovery. The O-CCH/PCL scaffold provides a promising new path for developing an optimal therapeutic alternative for peripheral nerve reconstruction. STATEMENT OF SIGNIFICANCE: Scaffolds with inner fillers displaying directional guidance cues represent a promising candidate for nerve repair. However, further clinical translation should pay attention to the problem of non-uniform distribution of inner fillers, the porosity and mechanical properties of the outer sheath and the morphological design facilitating operation. In this study, a stage-wise fabrication strategy was used, which made it possible to develop an O-CCH/PCL compound scaffold with a uniform longitudinally oriented inner filler and a porous outer sheath. The uniform distribution of the pores in the O-CCH/PCL scaffold provides a solution to resolve the problem of non-uniform distribution of inner fillers, which impede the clinical translation of scaffolds with longitudinal microstructured fillers, especially for aligned-fiber-based scaffolds. In vitro and in vivo studies indicated that the O-CCH/PCL scaffolds could provide topographical cues for axonal regeneration and SC migration, which were not found for random scaffolds (with random microstructure resemble sponge-based scaffolds). The electrospun porous PCL sheath of the O-CCH/PCL scaffold not only prevented fibroblast infiltration, but also satisfied the mechanical requirements for clinical use, paving the way for clinical translation. The differential degradation time of the O-CCH filler and the PCL sheath makes O-CCH/PCL scaffold able to provide long protection for regenerating axons from compression stress, but enough space for regenerating nerve. These findings highlight the possibility of developing an optimal therapeutic alternative for nerve defects using the O-CCH/PCL scaffold.

In Vivo Imaging-Guided Photothermal/Photoacoustic Synergistic Therapy with Bioorthogonal Metabolic Glycoengineering-Activated Tumor Targeting Nanoparticles.

Developing multifunctional phototheranostics with nanoplatforms offers promising potential for effective eradication of malignant solid tumors. In this study, we develop a multifunctional phototheranostic by combining photothermal therapy (PTT) and photoacoustic therapy (PAT) based on a tumor-targeting nanoagent (DBCO-ZnPc-LP). The nanoagent DBCO-ZnPc-LP was facilely prepared by self-assembling of a single lipophilic near-infrared (NIR) dye zinc(II)-phthalocyanine (ZnPc) with a lipid-poly(ethylene glycol) (LP) and following modified further with dibenzyl cyclootyne (DBCO) for introducing the two-step chemical tumor-targeting strategy based on metabolic glycoengineering and click chemistry. The as-prepared DBCO-ZnPc-LP could not only convert NIR light into heat for effective thermal ablation but also induce a thermal-enhanced ultrasound shockwave boost to trigger substantially localized mechanical damage, achieving synergistic antitumor effect both in vitro and in vivo. Moreover, DBCO-ZnPc-LP can be efficiently delivered into tumor cells and solid tumors after being injected intravenously via the two-step tumor-targeting strategy. By integrating the targeting strategy, photoacoustic imaging, and the synergistic interaction between PTT and PAT, a solid tumor could be accurately positioned and thoroughly eradicated in vivo. Therefore, this multifunctional phototheranostic is believed to play an important role in future oncotherapy by the enhanced synergistic effect of PTT and PAT under the guidance of photoacoustic imaging.

Dipentaerythritol penta-/hexa-acrylate based-highly cross-linked hybrid monolithic column: Preparation and its applications for ultrahigh efficiency separation of proteins.

In this study, multi-acrylate based dipentaerythritol penta-/hexa-acrylate (DPEPA) was exploited for fabrication of highly cross-linked hybrid monolithic column by copolymerization with polyhedral oligomeric silsesquioxane methacryl substituted (POSS-MA) via a "one-pot" method. The new DPEPA-POSS hybrid monolithic column was respectively characterized by Fourier transform infrared spectrometry, thermogravimetric analysis, scanning electron microscopy and nitrogen adsorption/desorption measurement. When it was used for the separation of amides, thioureas and positional isomers of phenols, ultrahigh column efficiency separation (up to 511,000 N m-1) was achieved with excellent selectivity. Moreover, intact protein standards could be efficiently separated with minimum tailing peaks, outperforming the commercially available silica-based C8 column. Furthermore, successful separation of complex egg white proteins and expressed BARD1 BRCT domains protein sample was also achieved with good chromatographic performance. In the future work, the DPEPA-POSS hybrid monolithic column will be further exploited and applied in capillary electrochromatography as well as the top-down based proteome research.