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Caldicellulosiruptor bescii is a cellulolytic bacterium that secretes multifunctional glycoside hydrolases for efficient hydrolysis of lignocellulose into fermentable sugars. Additionally, some abundant noncatalytic proteins accompanying multifunctional glycoside hydrolases are also secreted by C. bescii, but its function has not yet been demonstrated. In this study, noncatalytic protein Athe_0181 and multifunctional glycoside hydrolases CbMan5C/Cel5A were expressed and purified from Escherichia coli BL21(DE3). Effective binding capacity of Athe_0181 to lignocellulose was displayed, and it showed preferential affinity to rice straw. Athe_0181 was shown to be a cellulase synergistic protein. It exhibited high synergistic activity of 523% in the presence of 25 μg/mL of CbMan5C/Cel5A with microcrystalline cellulose as the substrate. The structure-modifying activity of Athe_0181 to microcrystalline cellulose was demonstrated by scanning electron microscopy and X-ray diffraction analysis. These characteristics demonstrated that Athe_0181 played a role in the synergism of glycoside hydrolases from C. bescii for efficient hydrolysis of lignocellulose.

In order to realise the biocompatibility and antibacterial activity of Ti alloy to meet the requirements of oral and orthopaedic applications, drug-loaded hydroxyapatite coatings doped with stronti...

BackgroundOsteoporosis affects the mandible resulting in bone loss. Though impairments are not life threatening, they affect a person's quality-of-life particularly vulnerable elderly. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in regulating bone metabolism. Autophagy is evolutionarily conserved intracellular self-degradation process and is vital in the maintenance of both miRNA and bone homeostasis. However, the role of autophagy in the pathogenesis of miRNA regulating osteoporosis remains unclear.MethodsIn the study, we established a rat osteoporosis model induced by ovariectomy (OVX) and isolated mesenchymal stem cells from mandible (MMSCs-M). Several miRNAs were identified to regulate osteoporosis in some studies. qRT-PCR was applied to examine the expression of miRNA, autophagy and osteogenic differentiation-related genes. Western blotting assays were performed to detect the expression of autophagy and osteogenic differentiation proteins. Immunofluorescence and transmission electron microscope were used to verify the autophagy activity. Transfecting technology was used to enhance or suppress the expression of miR-152-5p which enable us to observe the relationship between miR-152-5p, autophagy and osteogenic differentiation. Additionally, the measurement of reactive oxygen species was used to investigate the mechanism of autophagy affecting osteogenic differentiation.ResultsWe found an upregulated expression of miR-152-5p in MMSCs-M in OVX group. Downregulated autophagy-related gene, proteins and autophagosome were detected invitroof OVX group compared with sham group. Moreover, downregulation of miR-152-5p promoted osteogenic differentiation of MMSCs-M as well as enhanced autophagy-related proteins in OVX group. Conversely, overexpression of miR-152-5p showed opposite effect in sham group. Meanwhile, we foundAtg14(autophagy-related protein homolog 14) was identified to be a direct target of miR-152-5p theoretically and functionally. In other words, we confirmed inhibition of miR-152-5p promoted the osteogenic differentiation via promoting ATG14-mediated autophagy. Furthermore, miR-152-5p/ATG14-mediated autophagy regulated osteogenic differentiation by reducing the endogenous ROS accumulation and maintaining cellular redox homeostasis.ConclusionOur data suggest that miR-152-5p is the first identified to regulate osteogenic differentiation by directly targeting autophagy-related protein ATG14 and regulating oxidative stress and therapeutic inhibition of miR-152-5p may be an efficient anabolic strategy for osteoporosis.

An ophthalmic solution of naringenin (NAR) based on dipotassium glycyrrhizinate (DG) micelle solubilization, called DG-NAR, was prepared, and its effect on dry eye disease (DED) was evaluated. DG-NAR was a clear, colorless aqueous solution with small micelle size (24.75±0.52 nm), narrow size distribution of polydispersity index 0.273±0.160, and a high entrapment efficiency (99.67±0.51%). The solution also revealed good storage stability in a 12-week short-term storage evaluation; it also displayed good vivo ocular tolerance in rabbit eyes investigated via a slit lamp observation and histopathological examination. When observed under fluorescence microscopy, the solution further exhibited improved in vivo corneal permeation profiles in mice eyes. As expected, in a BAC-induced DED mouse model, ocular topical administration of DG-NAR achieved a remarkable efficacy against dry eye symptoms when compared to the DGNAR physical mixture solution or free NAR solution; this included decreased rose bengal and fluorescein staining, increased tear volume and corneal sensitivities, alleviated histopathological symptoms, and reversed corneal epithelium and endothelium damages. Additionally, performance in some efficacy evaluation parameters were better than in the commercialized 0.1% hyaluronic acid sodium salt eye drops. This therapeutic effect can be attributed to the mechanisms regulating HMGB1 signaling and its related proinflammatory cytokines. Together, these in vitro/in vivo results suggested that this novel phytochemical-based nanoformulation of DG-NAR may be a promising candidate in the efficacious treatment of DED.

Objective Medication-related osteonecrosis of the jaw (MRONJ) is the main adverse side effect of bisphosphonates (BPs), mainly owing to the inhibitory effect of BPs on osteoclastogenesis. CircRNAs were identified to be an important factor in regulating cellular processes. The aim of this study was to explore the effect of mmu_circ_0001066 on BP-inhibited osteoclastogenesis. Materials and methods The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Bioinformatics techniques were applied to screen potential circRNAs. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were used to examine the effect of mmu_circ_0001066 on osteoclastogenesis. Bioinformatics analysis, luciferase reporter assays, and Western blotting assays were performed to investigate the underlying mechanism. Results Four MRONJ-related miRNAs were upregulated in BP-treated RAW264.7 cells and the expression of mmu_circ_0001066 was negatively correlated with those of MRONJ-related miRNAs. Furthermore, the upregulation of mmu_circ_0001066 partially attenuated the inhibitory effect of BP on osteoclastogenesis in RAW264.7 cells. Mechanistically, upregulated miR-16 suppressed osteoclastogenesis and miR-16 inhibitor increased osteoclastogenesis. Furthermore, we have identified that miR-16 is a downstream effector of mmu_circ_0001066. Conclusion Our results suggest that mmu_circ_0001066 played an important role in the BP-mediated suppression of osteoclastogenesis, which lays a foundation for identifying mmu_circ_0001066 as a potential biomarker for MRONJ.

Bonding has been used to repair carbon fiber-reinforced polymer (CFRP) materials. However, research has shown that resin residue on the surface of CFRP can cause adhesion problems. Therefore, a reliable surface cleaning procedure is necessary to remove the resin residue before bonding. In this paper, the surface resin was removed by laser cleaning, while the surface properties of CFRP were improved. A pulsed laser cleaning experiment was designed to study the chemical activity and bonding strength of CFRP treated by laser with different laser power and scanning speed. The results showed that as the contact angle of the material surface decreased, chemical activity and adhesive properties were improved. The surface pretreated with laser power of 16 W (scanning speed of 1500 mm/s) had no resin residue and the best adhesive properties; the bonding strength was 1.6 times higher than that of the untreated surface, and the failure mode was dominated by a cohesive damage mode.

Cloud service based on data center network (DCN) has become an attractive choice for various applications. Traditionally, multiple DCs are distributed at different nodes across a given optical network, and users access DCs through predefined routes (this architecture is named as Multiple Independent DCN, MI-DCN). However, as there exist transmission delay and failure probability on each link, such a network may not be a good choice for the service providers from the perspective of service reliability and cost. Therefore, we propose the idea of regrouping all the racks and distributing each rack group on a special node, where there exists a gateway (this architecture is named as Integrated Distributed DCN, ID-DCN). As each group can provide service independently, by properly grouping and routing, the whole network can work more efficiently with lower cost and higher reliability. In this paper, we study the service provision in the above two types of DCN. With the given failure probability and transmission delay on each link, we aim to minimize the total service cost and design the access routes for the demands originated from each node. To integrate the system cost, we introduce two cost scaling factors for delay and failure probability, which can be flexibly adjusted to control their relative importance (i.e., the weights). Based on mathematical approximation, a novel method is proposed to compute the failure probabilities of individual service paths. This translates our objective function into a linear expression. Then, we formulate two integer linear programs (ILP) to compare the solutions of the two scenarios. Via extensive numerical experiments, the performance of the two schemes is properly verified.

We consider differentiated timecritical task scheduling in a N×N input queued optical packet switch to ensure 100% throughput and meet different delay requirements among various modules of data center. Existing schemes either consider slot-by-slot scheduling with queue depth serving as the delay metric or assume that each input-output connection has the same delay bound in the batch scheduling mode. The former scheme neglects the effect of reconfiguration overhead, which may result in crippled system performance, while the latter cannot satisfy users’ differentiated Quality of Service (QoS) requirements. To make up these deficiencies, we propose a new batch scheduling scheme to meet the various portto- port delay requirements in a best-effort manner. Moreover, a speedup is considered to compensate for both the reconfiguration overhead and the unavoidable slots wastage in the switch fabric. With traffic matrix and delay constraint matrix given, this paper proposes two heuristic algorithms Stringent Delay First (SDF) and m-order SDF(m-SDF) to realize the 100% packet switching, while maximizing the delay constraints satisfaction ratio. The performance of our scheme is verified by extensive numerical simulations.

We consider unbalanced traffic distribution in a three-stage Clos switching network for datacenters to ensure 100% throughput and minimize traffic delay by balancing bandwidth utilization. Existing traffic scheduling algorithms with packet delay bound guarantee neglect the fact that unbalanced demands may lead to poor bandwidth utilization and thus lead to poor switching performance. To make up these deficiencies, we propose an efficient multiple hops strategy (MHS). MHS can well utilize internal bandwidth of the switch to achieve load balancing. As the first step of MHS, we first propose a naive algorithm AHF (Average Heavy-Traffic First) to decompose the traffic matrix by taking load balancing into account. By shifting and transmitting packets using those empty time slots (i.e., not-yet-utilized slots) in the configurations generated by AHF, the second step of MHS is achieved to minimize packet delay via a better load balancing strategy. Simulation results confirm that MHS outperforms the naive AHF algorithm by effectively reducing packet delay bound guarantee.

Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future.

We consider differentiated time-critical task scheduling in an N × N optical packet switch to ensure 100% throughput and meet different delay requirements among various modules of data center networks (DCNs). Existing algorithms assume that each input-output connection has the same delay bound, which cannot satisfy users' differentiated QoS requirements. To make up this deficiency, we propose a new scheduling scheme to meet the delay requirements in a best-effort manner. Moreover, a speedup is considered to compensate for both the reconfiguration overhead and the unavoidable slots wastage in the switch fabric. With traffic matrix and delay constraint matrix given, this paper proposes an algorithm SDF (Strict Delay First) to realize the packet switching, while minimizing the required speedup. The performance of our scheme is verified by extensive numerical simulations.

Physical machines (PMs) constitute the hardware infrastructure in data centers. Proper distribution and placement of PMs plays an important role in determining the system performance. Existing PM placement approaches generally ignore the demands of virtual machines (VMs), resulting in a poor resource utilization and service QoS. In this paper, we focus on the PM placement problem in a given optical network (called the optical layer) with given traffic demands on the VM-layer. By jointly considering optical and VM layers, we formulate an ILP (Integer Linear Program) to shape the PM-layer topology, while minimizing the overall cost of PM placement and VM mapping. To combine delay and transmission costs on each optical link, we define a cost factor θ, which can be used to adjust the impact of service delay. Extensive numerical simulations are carried out to validate the correctness of our ILP and the flexibility of our scheme.

With the widespread usage of cloud service, data center networks (DCNs), serving as the underlying supporting platform becomes increasingly important. However, the traditional centralized DCNs are not so scalable and efficient to meet the rapid growth of service demands. Therefore, we propose to split the racks of a DCN into multiple groups and distribute them in a given optical network. With given transmission delay and failure probability of each link as well as DCN internal and external traffic loads, we try to realize the distributed DCN and minimize the total cost. To combine delay and failure costs together, we introduce two cost scaling factors, which can be flexibly adjusted to control their relative importance (i.e., weights) and satisfy various performance targets. Then, we formulate an integer linear program (ILP) to solve the network planning problem and carry out extensive numerical simulations to validate the performance of our scheme.