Sepiolite-Supported Manganese Oxide as an Efficient Catalyst for Formaldehyde Oxidation: Performance and Mechanism.

The current study involved the preparation of a number of MnOx/Sep catalysts using the impregnation (MnOx/Sep-I), hydrothermal (MnOx/Sep-H), and precipitation (MnOx/Sep-P) methods. The MnOx/Sep catalysts that were produced were examined for their ability to catalytically oxidize formaldehyde (HCHO). Through the use of several technologies, including N2 adsorption-desorption, XRD, FTIR, TEM, H2-TPR, O2-TPD, CO2-TPD, and XPS, the function of MnOx in HCHO elimination was examined. The MnOx/Sep-H combination was shown to have superior catalytic activities, outstanding cycle stability, and long-term activity. It was also able to perform complete HCHO conversion at 85 °C with a high GHSV of 6000 mL/(g·h) and 50% humidity. Large specific surface area and pore size, a widely dispersed active component, a high percentage of Mn3+ species, and lattice oxygen concentration all suggested a potential reaction route for HCHO oxidation. This research produced a low-cost, highly effective catalyst for HCHO purification in indoor or industrial air environments.

CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis.

Aims: To investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. Results: Transcriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. Conclusion: CPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

Arctium lappa L. polysaccharides enhanced the therapeutic effects of nasal ectomesenchymal stem cells against liver fibrosis by inhibiting the Wnt/ß-catenin pathway.

The oxidative microenvironment in fibrotic livers often diminishes the effectiveness of mesenchymal stem cells (MSCs)-based therapy. Recent research suggests that pharmacological pre-treatment could enhance the therapeutic performance of MSCs. In this study, we assessed the impact of Arctium lappa L. polysaccharides (ALP) on the biological properties of nasal ectomesenchymal stem cells (EMSCs) and investigated the augmenting effect of ALP pretreatment on EMSCs (ALP-EMSCs) for the treatment of liver fibrosis. ALP treatment demonstrated multiple biological impacts on EMSC functions regarding liver fibrosis: firstly, it maintained the stemness of the cells while boosting the EMSCs' paracrine effects; secondly, it increased the expression of anti-inflammatory and antioxidant factors; thirdly, it inhibited the activation of hepatic stellate cells (HSCs) and liver collagen build-up by modulating the Wnt/ß-catenin signaling pathways. Collectively, these effects helped to halt the progression of liver fibrosis. Therefore, the use of ALP-EMSCs presents an innovative and promising approach for treating hepatic fibrosis in clinical scenarios.

Single-walled carbon nanotubes synthesized by laser ablation from coal for field-effect transistors.

Single-walled carbon nanotubes (SWCNTs) have been attracting extensive attention due to their excellent properties. We have developed a strategy of using coal to synthesize SWCNTs for high performance field-effect transistors (FETs). The high-quality SWCNTs were synthesized by laser ablation using only coal as the carbon source and Co-Ni as the catalyst. We show that coal is a carbon source superior to graphite with higher yield and better selectivity toward SWCNTs with smaller diameters. Without any pre-purification, the as-prepared SWCNTs were directly sorted based on their conductivity and diameter using either aqueous two-phase extraction or organic phase extraction with PCz (poly[9-(1-octylonoyl)-9H-carbazole-2,7-diyl]). The semiconducting SWCNTs sorted by one-step PCz extraction were used to fabricate thin film FETs. The transformation of coal into FETs (and further integrated circuits) demonstrates an efficient way of utilizing natural resources and a marvelous example in green carbon technology. Considering its short steps and high feasibility, it presents great potential in future practical applications not limited to electronics.

Adaptation of Droplet Digital PCR-Based HIV Transcription Profiling to Digital PCR and Association of HIV Transcription and Total or Intact HIV DNA.

In most people living with HIV (PLWH) on effective antiretroviral therapy (ART), cell-associated viral transcripts are readily detectable in CD4+ T cells despite the absence of viremia. Quantification of HIV RNA species provides insights into the transcriptional activity of proviruses that persist in cells and tissues throughout the body during ART ('HIV reservoir'). One such technique for HIV RNA quantitation, 'HIV transcription profiling', developed in the Yukl laboratory, measures a series of HIV RNA species using droplet digital PCR. To take advantage of advances in digital (d)PCR, we adapted the 'HIV transcription profiling' technique to Qiagen's dPCR platform (QIAcuity) and compared its performance to droplet digital (dd)PCR (Bio-Rad QX200 system). Using RNA standards, the two technologies were tested in parallel and assessed for multiple parameters including sensitivity, specificity, linearity, and intra- and inter-assay variability. The newly validated dPCR assays were then applied to samples from PLWH to determine HIV transcriptional activity relative to HIV reservoir size. We report that HIV transcriptional profiling was readily adapted to dPCR and assays performed similarly to ddPCR, with no differences in assay characteristics. We applied these assays in a cohort of 23 PLWH and found that HIV reservoir size, based on genetically intact proviral DNA, does not predict HIV transcriptional activity. In contrast, levels of total DNA correlated with levels of most HIV transcripts (initiated, proximally and distally elongated, unspliced, and completed, but not multiply spliced), suggesting that a considerable proportion of HIV transcripts likely originate from defective proviruses. These findings may have implications for measuring and assessing curative strategies and clinical trial outcomes.

Technical modelling of solar photovoltaic water pumping system and evaluation of system performance and their socio-economic impact.

Water is a precious resource for agriculture and most of the land is irrigated by tube wells. Diesel engines and electricity-operated pumps are widely used to fulfill irrigation water requirements; such conventional systems are inefficient and costly. With rising concerns about global warming, it is important to choose renewable energy source. In this study, SPVWPS has been optimally designed considering the water requirement, solar resources, tilt angle and orientation, losses in both systems and performance ratio. A PVSyst and SoSiT simulation tools were used to perform simulation analysis of the designed solar photovoltaic WPS. After designing and performance analysis, farmers were interviewed during fieldwork to assess socioeconomic impacts. In the result section, performance of PV system is analyzed at various tilt angles and it is established that system installed at a 15° tilt angle is more efficient. The annual PV array virtual energy at MPP of designed photovoltaic system is 33342 kWh and the annual energy available to operate the WPS is 23502 kWh. Module array mismatch and ohmic wiring losses are 374.16 kWh and 298.83 kWh, respectively. The total annual water demand of the selected site is 80769 m³ and designed SPWPS pumped 75054 m³ of water, supplying 92.93% of the irrigation demand. The normalized values of the effective energy, system losses, collection losses and unused energy in the SPVWP system are 2.6 kW/kWp/day, 0.69 kW/kWp/day, 0.72 kW/kWp/day and 0.48 kW/kWp/day, respectively. The annual average performance ratio of the proposed system is 74.62%. The results of the interviews showed that 70% of farmers are extremely satisfied with the performance of SPVWPS and 84% of farmers indicated that they did not incur any operating costs. The unit cost of the SPWPS is 0.17 €/kWh, which is 56.41% and 19.04% less expensive than the cost of diesel and grid electricity.

Mimicking bone matrix through coaxial electrospinning of core-shell nanofibrous scaffold for improving neurogenesis bone regeneration.

There is a significant clinical demand for bone repair materials with high efficacy. This study was designed to fabricate nanofibrous scaffolds to promote bone defect regeneration using magnesium doped mesoporous bioactive glass (MBG), a fusion protein Osteocalcin-Osteopontin-Biglycan (OOB), silk fibroin (SF) and nerve growth factor (NGF) for facilitating accelerated bone formation. We found that MBG adsorbed with OOB (OOB@MBG) as core, and SF adsorbed with NGF (SF@NGF) as shell to fabricate the nanofibrous scaffolds (OOB@MBG/NGF@SF) through coaxial electrospinning. OOB@MBG/NGF@SF scaffolds could effectively mimic the component and structure of bone matrix. Interestingly, we observed that OOB@MBG/NGF@SF scaffolds could substantially promote bone mesenchymal stem cells (BMSCs) osteogenesis through stimulating Erk1/2 activated Runx2 and mTOR pathway, and it could also activate the expression level of various osteogenic marker genes. Intriguingly, OOB@MBG/NGF@SF scaffolds could also enhance BMSCs induced neural differentiation cells differentiated into neuron, and activate the expression of the different neuron specific marker genes. Moreover, it was found that OOB@MBG/NGF@SF scaffolds accelerated bone regeneration with neurogenesis, and new neurons were formed in Haversian canal in vivo. Consistent with these observations, we found that Erk1/2 and mTOR signaling pathways also regulated osteogenesis with the neurogenesis process from RNA sequencing result. Overall, our findings provided novel evidence suggesting that OOB@MBG/NGF@SF scaffolds could function as a potential biomaterial in accelerating bone defect regeneration with neurogenesis, as well as in recovering the motor ability and improving the quality of life of patients.

Enterobacter sp. Strain SM1_HS2B Manifests Transient Elongation and Swimming Motility in Liquid Medium.

Many species of bacteria change their morphology and behavior under external stresses. In this study, we report transient elongation and swimming motility of a novel Enterobacter sp. strain, SM1_HS2B, in liquid broth under a standard growth condition. When growing in the Luria-Bertani medium, HS2B cells delay their cell division and elongate. Although transient over a few hours, the average cell length reaches over 10 times that of the stationary-state cells. The increase is also cumulative following repeated growth cycles stimulated by taking cells out of the exponential phase and adding them into fresh medium every 2 hours. The majority of the cells attain swimming motility during the exponential growth phase, and then they lose swimming motility over the course of several hours. Both daughter cells due to division of a long swimming cell retain the ability to swim. We confirm that the long HS2B cells swim with rigid-body rotation along their body axis. These findings based on microscopic observation following repeated cycles of growth establish HS2B as a prototype strain with sensitive dependence of size and motility on its physical and biochemical environment. IMPORTANCE Bacteria undergo morphological changes in order to cope with external stresses. Among the best-known examples are cell elongation and hyperflagellation in the context of swarming motility. The subject of this report, SM1_HS2B, is a hyperswarming strain of a newly identified species of enterobacteria, noted as Enterobacter sp. SM1. The key finding that SM1_HS2B transiently elongates to extreme length in fresh liquid medium offers new insights on regulation in bacterial growth and division. SM1_HS2B also manifests transient but vigorous swimming motility during the exponential phase of growth in liquid medium. These properties establish HS2B as a prototype strain with sensitive dependence of size and motility on its physical and biochemical environment. Such a dependence may be relevant to swarming behavior with a significant environmental or physiological outcome.

Jejunal Gastrointestinal Stromal Tumor (GIST) as a Rare Cause of GI Bleed: A Case Report.

Jejunal gastrointestinal stromal tumor (GIST) is a rare cause of recurrent gastrointestinal bleeding (GIB). Early diagnosis for patients with jejunal GIST is often challenging, which can lead to delays in treatment. We present a case of a 32-year-old male patient with persistent abdominal pain and hematemesis despite treatment for gastroesophageal reflux disease (GERD). Upon initial ER visit, CT result was consistent with intra-abdominal abscess and the patient underwent interventional radiology (IR) drainage. On a second ER visit three weeks later, CT showed a suspicious lesion in the small bowel. The patient underwent exploratory laparoscopy which revealed a mass in the jejunum. The lesion was resected successfully and pathology report confirmed the diagnosis of GIST with positive immunohistochemistry marker cluster of differentiation (CD)117. The patient was discharged with no complications post-operatively. In conclusion, recurrent GIB and unusual imaging findings should raise clinical suspicion for alternative causes for GIB, including tumors such as GIST.

New insights on folliculogenesis and follicular placentation in marine viviparous fish black rockfish (Sebastes schlegelii).

In viviparous fish, a considerable degree of variation in placental structures have been described. However, no distinct structures are reported in Scorpaenidae. In this study, we demonstrate a new type of folliculogenesis and follicular placentation in Sebastes schlegelii. Before copulation, the germinal epithelium gradually surrounds the oocytes and develops into individually follicles with a stalk-like structure hanging on the ovigerous lamella, which ensures each follicle have access to spermatozoa after copulation. From V to early gestation stage, the cyp17-I highly expressesaccompanied by cyp19a1a signals disappearance, and 11-ketotestosterone level keeps rising and peaks at blastula stage, while 17ß-estradiol declines to the bottom. Meanwhile, the theca cells rapidly proliferate and invade outwards forming a highly hypertrophied and folded microvillous placenta. This unbalance of hormone might be an important factor driving the theca cells proliferation and invasion. Additionally, some conserved genes related to mammalian placentation are significantly high expression in follicular placenta suggesting the high convergence in vertebrate placenta evolution.

PCL nanofibrous incorporating unique matrix fusion protein adsorbed mesoporous bioactive glass for bone tissue engineering.

Mesoporous bioactive glass (MBG) is a potential biomedical material in bone defect repairment because of its bioactivity, biocompatibility, and osteoinduction properties. Here we report that Mg-doped MBG scaffold with 3:1 Ca/Mg ratio (MBG-Ca/Mg-3) is good for MC3T3-E1 osteoblast differentiation and mineralization. Mimicking bone extracellular matrix structure by electrospinning, we used MBG-Ca/Mg-3 adsorbed with Osteocalcin-Osteopontin-Biglycan (OOB), a new unique matrix fusion protein, to form OOB@MBG-Ca/Mg-3 scaffold, which has multifunctional ability in calvarial bone defect repairment in vivo. Intriguingly, we found that OOB@MBG-Ca/Mg-3 scaffold increases the expression of osteoblastic marker genes, including bone morphogenetic protein (Bmp2), osteopontin (Opn), Osterix, Runx2 through activation of ERK1/2. We concluded that OOB@MBG-Ca/Mg-3 scaffold promotes osteoblast differentiation and mineralization through ERK1/2 pathway and it can also enhance bone formation in vivo, which provides a new biomaterial in bone tissue engineering.

Erratum: Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy: Erratum.

[This corrects the article DOI: 10.7150/thno.47408.].

Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX-induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX-induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM- and Akk-induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX-induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM-induced anti-osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.

Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy.

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aß). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aß levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aß in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aß clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

Bioinspired membrane provides periosteum-mimetic microenvironment for accelerating vascularized bone regeneration.

Periosteum plays a pivotal role in vascularization, ossification and remodeling during the healing process of bone injury. However, there are few studies focused on the construction of artificial implants with periosteum-mimetic effect. To emulate the primary role of natural periosteum or endosteal tissues in bone regeneration, here we provide a functional biomimetic membrane with micropatterns of site-specific biomineralization. The micropattern is generated by using printed hydroxyapatite nanoparticles (HANPs), combined with selective growth of biomineralized apatite and in situ coprecipitation with growth factors. The biomimetic membrane can sustainably provide a periosteum-mimetic microenvironment, such as long-term topographical guidance for cell recruitment and induced cell differentiation, by releasing calcium phosphate and growth factors. We demonstrated that rat mesenchymal stem cells (rMSCs) on such biomimetic membrane exhibited highly aligned organization, leading to enhanced angiogenesis and osteogenesis. In the rat calvarial defect model, our biomimetic membranes with biomineralized micropatterns could significantly enhance vascularized ossification and accelerate new bone formation. The current work suggests that the functionally biomimetic membranes with specific biomineralized micropatterns can be a promising alternative to periosteal autografts, with great potential for bench-to-bedside translation in orthopedics.

Characterization of CYP26B1-Selective Inhibitor, DX314, as a Potential Therapeutic for Keratinization Disorders.

Inhibition of CYP450-mediated retinoic acid (RA) metabolism by RA metabolism blocking agents increases endogenous retinoids and is an alternative to retinoid therapy. Currently available RA metabolism blocking agents (i.e., liarozole and talarozole) tend to have fewer adverse effects than traditional retinoids but lack target specificity. Substrate-based inhibitor DX314 has enhanced selectivity for RA-metabolizing enzyme CYP26B1 and may offer an improved treatment option for keratinization disorders such as congenital ichthyosis and Darier disease. In this study, we used RT-qPCR, RNA sequencing, pathway, upstream regulator, and histological analyses to demonstrate that DX314 can potentiate the effects of all-trans-RA in healthy and diseased reconstructed human epidermis. We unexpectedly discovered that DX314, but not all-trans-RA or previous RA metabolism blocking agents, appears to protect epidermal barrier integrity. In addition, DX314-induced keratinization and epidermal proliferation effects are observed in a rhino mice model. Altogether, the results indicate that DX314 inhibits all-trans-RA metabolism with minimal off-target activity and shows therapeutic similarity to topical retinoids in vitro and in vivo. Findings of a barrier-protecting effect require further mechanistic study but may lead to a unique strategy in barrier-reinforcing therapies. DX314 is a promising candidate compound for further study and development in the context of keratinization disorders.

Air pollution as a determinant of food delivery and related plastic waste.

Plastic waste is a growing environmental concern. The food delivery industry is criticized for its environmental impact, especially its current use of plastic packaging. At the same time, the environment impacts the industry. We show that air pollution is a behavioural driver of food delivery consumption in the urban developing world. Our hypothesis is that individuals are more likely to order delivery when their personal cost of exposure to the outdoor environment rises. We surveyed office workers in three Chinese cities and found that an increase of 100 µg m-3 in particulate matter pollution (PM2.5) raised the propensity to order food delivery by two-fifths of the sample mean. We used photographic evidence to quantify disposable plastic in meal delivery. Data from an online delivery platform with a broad customer base indicate a smaller, but still substantial, causal link between air quality and food delivery. Overall, air pollution control brings plastic waste co-benefits.

Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3.

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn-/ - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn-/ - mice or infecting optn-/ - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn-/ - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP.Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; µCT: micro computed tomography.

In vitro and in vivo osteogenesis up-regulated by two-dimensional nanosheets through a macrophage-mediated pathway.

Two-dimensional (2D) nanomaterials are attracting more and more interest in regenerative medicine due to their unique properties; however 2D biomimetic calcium mineral has not yet been developed and demonstrated application for bone tissue engineering. Here we described a novel calcium phosphate material with a 2D nanostructure that was synthesized using collagen and sodium alginate as the template. In vitro performance of the nanocrystalline material was evaluated, and we found that 2D CaP nanoparticles (NPs) enhanced the in vitro osteogenic differentiation of rat mesenchymal stem cells (rMSCs) through a macrophage-mediated signal pathway, when co-cultured with RAW 264.7 cells, rather than direct NP/stem cell interaction. A 2D topology structured surface was constructed by encapsulating the CaP nanomaterials in a gelatin hydrogel, which was demonstrated to be able to mediate in vivo ossification through a macrophage polarization related pathway in a femur defect rat model, and allowed the optimal therapeutic outcome compared to normal CaP counterparts. Our current work may have enlightened a new mechanism regarding NP-induced stem cell differentiation through immunoregulation, and the 2D CaP encapsulated hydrogel scaffold may serve as a potential alternative to autograft bone for orthopedic applications.

Ångstrom-scale silver particle-embedded carbomer gel promotes wound healing by inhibiting bacterial colonization and inflammation.

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.