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Abstract Refractory high-entropy alloys (RHEAs) are of interest for ultrahigh-temperature applications. To overcome their drawbacks — low-temperature brittleness and poor creep strength at high temperatures — improved fundamental understanding is needed. Using experiments, theory, and modeling, we investigated prototypical body-centered cubic (BCC) RHEAs, TiZrHfNbTa and VNbMoTaW. The former is compressible to 77 K, whereas the latter is not below 298 K. Hexagonal close-packed (HCP) elements in TiZrHfNbTa lower its dislocation core energy, increase lattice distortion, and lower its shear modulus relative to VNbMoTaW whose elements are all BCC. Screw dislocations dominate TiZrHfNbTa plasticity, but equal numbers of edges and screws exist in VNbTaMoW. Dislocation cores are compact in VNbTaMoW and extended in TiZrHfNbTa, and different macroscopic slip planes are activated in the two RHEAs, which we attribute to the concentration of HCP elements. Our findings demonstrate how ductility and strength can be controlled through the ratio of HCP to BCC elements in RHEAs.

Verticillium wilt, caused by Verticillium dahliae, is a soil-borne disease affecting eggplant. Wild eggplant, recognized as an excellent disease-resistant resource against verticillium wilt, plays a pivotal role in grafting and breeding for disease resistance. However, the underlying resistance mechanisms of wild eggplant remain poorly understood. This study compared two wild eggplant varieties, LC-2 (high resistance) and LC-7 (sensitive) at the phenotypic, transcriptomic, and metabolomic levels to determine the molecular basis of their resistance to verticillium wilt. These two varieties exhibit substantial phenotypic differences in petal color, leaf spines, and fruit traits. Following inoculation with V. dahliae, LC-2 demonstrated significantly higher activities of polyphenol oxidase, superoxide dismutase, peroxidase, phenylalanine ammonia lyase, β-1,3 glucanase, and chitinase than did LC-7. RNA sequencing revealed 4,017 differentially expressed genes (DEGs), with a significant portion implicated in processes associated with disease resistance and growth. These processes encompassed defense responses, cell wall biogenesis, developmental processes, and biosynthesis of spermidine, cinnamic acid, and cutin. A gene co-expression analysis identified 13 transcription factors as hub genes in modules related to plant defense response. Some genes exhibited distinct expression patterns between LC-2 and LC-7, suggesting their crucial roles in responding to infection. Further, metabolome analysis identified 549 differentially accumulated metabolites (DAMs) between LC-2 and LC-7, primarily consisting of compounds such as flavonoids, phenolic acids, lipids, and other metabolites. Integrated transcriptome and metabolome analyses revealed the association of 35 gene–metabolite pairs in modules related to the plant defense response, highlighting the interconnected processes underlying the plant defense response. These findings characterize the molecular basis of LC-2 resistance to verticillium wilt and thus have potential value for future breeding of wilt-resistant eggplant varieties.

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvβ3 and α5β1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model.Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE.Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvβ3, and α5β1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16.Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

Abstract Background Excessive sugar intake has become a major challenge in modern societies. Stevioside is a promising non-calorie sweetener with anti-inflammatory effects; however, its effects on the oral environment and periodontitis remain unclear. Therefore, this study explores the effect of stevioside on periodontitis in mice. Methods Mice were divided into four groups, namely, control, treated with water, and periodontitis models, established using 5 − 0 silk sutures ligation around the second molar then infected the oral cavity with Porphyromonas gingivalis (P. gingivalis) viscous suspension, divided into three groups treated with 0.1% stevioside (P + S), 10% glucose (P + G), or water (P). Micro-CT scanning was used to assess alveolar bone resorption, while RT-PCR was used to evaluate the inflammatory factors expression and P. gingivalis invasion in the gingiva. The composition of the oral bacteria was analysed using 16 S rRNA sequence in the saliva. In addition, P. gingivalis was co-cultured with stevioside at different concentrations in vitro, and bacterial activity was detected via optical density values and live/dead staining. The virulence was detected using RT-PCR, while biofilm formation was detected using scanning electron microscopy. Results Compared with 10% glucose, treatment with 0.1% stevioside reduced alveolar bone absorption and osteoclasts while decreasing IL-6, TNF-α, IL-1β, and P. gingivalis in the gingiva of periodontitis mice. The CEJ-ABC distance in the P + S group was significantly lower than that in the P and P + G groups (P

Abstract Deep learning is one of the most powerful machine learning algorithms at present. The convolutional neural network model has the ability to automatically learn features, and has a greater performance advantage than other deep learning models in the field of image processing. Based on deep learning, the effects of platelet-rich plasma injection of betamethasone on shoulder pain and function in patients with partial rotator cuff injury were investigated. Eighty patients with tendinosis or a partial tear (

AbstractGradual loss of neuronal structure and function due to impaired blood–brain barrier (BBB) and neuroinflammation are important factors in multiple sclerosis (MS) progression. Our previous studies demonstrated that the C16 peptide and angiopoietin 1 (Ang-1) compound (C + A) could modulate inflammation and vascular protection in many models of MS. In this study, nanotechnology and a novel nanovector of the leukocyte chemotactic peptide N-formyl-methionyl-leucyl–phenylalanine (fMLP) were used to examine the effects of C + A on MS. The acute experimental autoimmune encephalomyelitis (EAE) model of MS was established in Lewis rats. The C + A compounds were conjugated to control nano-carriers and fMLP-nano-carriers and administered to animals by intravenous injection. The neuropathological changes in the brain cortex and spinal cord were examined using multiple approaches. The stimulation of vascular injection sites was examined using rabbits. The results showed that all C + A compounds (C + A alone, nano-carrier C + A, and fMLP-nano-carrier C + A) reduced neuronal inflammation, axonal demyelination, gliosis, neuronal apoptosis, vascular leakage, and BBB impairment induced by EAE. In addition, the C + A compounds had minimal side effects on liver and kidney functions. Furthermore, the fMLP-nano-carrier C + A compound had better effects compared to C + A alone and the nano-carrier C + A. This study indicated that the fMLP-nano-carrier C + A could attenuate inflammation-related pathological changes in EAE and may be a potential therapeutic strategy for the treatment of MS and EAE.

Abstract Background Childhood obesity was associated with retinochoroidal microvascular changes using optical coherence tomography angiography (OCTA), but obesity duration was neglected. Obesity is chronic and progressive and obesity duration is related to microvascular function. Thus, it is important to identify microvascular changes in obese children timely to allow possible interventions with the increase in the number of obese children. This pilot study aimed to characterize retinochoroidal microvascular changes in newly developed obese children compared to age- and sex-matched controls. Methods Forty newly developed obese children and 40 age- and sex-matched controls were recruited. All subjects completed comprehensive eye examinations, including axial length, cycloplegic refraction, optical coherence tomography angiography scans (AngioVue; Optovue Inc), etc. Results There were no statistically significant differences between groups in terms of month age (P = 0.927), spherical equivalent refraction (P = 0.753) and axial length (P = 0.196). Newly developed obese children had lower vessel density (VD) in the inferior parafovea (P = 0.026), nasal parafovea (P = 0.038) and temporal perifovea (P = 0.026) of deep vascular complex (DVC), higher VD in the fovea of superficial vascular complex (P = 0.021) and the fovea of DVC (P = 0.016), and smaller foveal avascular zone (P = 0.003) when compared to controls. Also, no apparent differences in any quadrant of total retinal thickness, subfoveal choroidal thickness (SFCT), and choriocapillaries fow voids were detected (all P > 0.05). Conclusion Retinochoroidal microvascular changes had already occurred in newly developed obese children, so early screening and close follow-up eye examinations were recommended; Retinal microvascular insult may precede its structural change and that retina may be a better candidate to predict the onset of retinochoroidal microvascular changes than choroid in obese children.

This paper investigates the average peak age-of-information (APAoI) in a cooperative wireless sensor network (WSN), which deploys non-orthogonal multiple access (NOMA) and simultaneous wireless information and power transfer (SWIPT) techniques. To assist the poor source–destination direct link, the relay can utilize the harvested energy to decode the superposition-coded signal sent by the source and send its decoded information to the remote destination. With the aim of minimizing APAoI for long-term transmission, we formulate an energy allocation policy problem to trade off rate, energy, and time under certain constraints. To overcome the difficulties caused by time-varying parameters and non-convexity constraints, we perform a quasi-static transformation to obtain a simplified optimization model and some energy allocation criteria. Based on this work, we propose a heuristic APAoI real-time adaptive optimization (APRAO) algorithm that decomposes the original problem into multiple sub-problems for each transmission. During the sub-problem solving process, we introduce the static energy allocation criteria, which let the obtained solutions help our APRAO algorithm track the optimal solution as the transmission number increases. Finally, we evaluate and verify the performance of the proposed algorithm through numerical experiments.

Helping behavior are actions aiming at assisting another individual in need or to relieve their distress. The occurrence of this behavior not only depends on automated physiological mechanisms, such as imitation or emotional contagion, that is, the individual’s emotion and physiological state matching with others, but also needs motivation to sustain. From a comparative and developmental perspective, we discover that the motivation for helping behavior has a deep foundation both phylogenetically and ontogenetically. For example, empathic concern for others, relieving personal distress and the desire for social contact are universal motivations across rodents, non-human primates and human early childhoods. Therefore, a circle-layered model integrating evidences for motivation for helping behavior from rodent to human early childhood research is proposed: the inner circle contains the emotional-behavioral system and the outer circle contains the affective-cognitive system. The application of this model has significance for both behavioral neuroscience research and cultivating prosocial behavior in human society.

Acupuncture has been used for centuries to heal the body; it is essential to comprehend the mechanism of acupuncture within the modern medical framework. By far much research provided a modern scientific understanding of how acupuncture works, most of them indicated that nervous system is involved. However, few studies have been conducted on how acupuncture trigger the nervous system. When the thin needle inserts the acupoint, the mechanical stress generated by acupuncture is the key factor of acupuncture effect. The first peripheral receptors activated in this process are mechanoreceptors, which are sensitive to mechanical forces. The purpose of this review is to explore the connection between the mechanoreceptors located in the skin and subcutaneous tissues and the acupuncture therapy. It also attempts to clue the possible roles of mechanoreceptors in the skin surface and subcutaneous tissue during the acupuncture manipulation and electroacupuncture.

Abstract Animal studies have indicated that increased blood-brain barrier (BBB) permeability and inflammatory cell infiltration are involved during the progression of Parkinson’s disease (PD). This study used C16, a peptide that competitively binds to integrin αvβ3 and inhibits inflammatory cell infiltration, as well as angiopoietin-1 (Ang-1), an endothelial growth factor crucial for blood vessel protection, to reduce inflammation and improve the central nervous system (CNS) microenvironment in murine models of PD. The combination of C16 and Ang-1 yielded better results compared to the individual drugs alone in terms of reducing dopaminergic neuronal apoptosis, ameliorating cognitive impairment, and electrophysiological dysfunction, attenuating inflammation in the CNS microenvironment, and improving the functional disability in PD mice or rats. These results suggest neuroprotective and anti-inflammatory properties of the C16 peptide plus Ang-1 in PD.

BackgroundEhlers-Danlos syndrome (EDS) spinal deformity type 2 has clinical features similar to those of spondyloepimetaphyseal dysplasia with joint laxity, type 1 (SEMDJL1). They have similar clinical manifestations and a similar genetic basis, both of which can be caused by mutations in the B3GALT6 gene. Hence, genetic screening and careful clinical examination are key to the differential diagnosis of these two diseases.Case presentationA 4-month-old boy was admitted to our hospital in order to find the causes of developmental delay. The clinical examination revealed that the child was delayed, with an excessive range of motion of joints, patent foramen ovale, and was accompanied by skin aging; the child was suspected to have EDS. However, unlike EDS, the child had normal muscle tension, and at the same time had a spinal deformity, mild kyphosis, widened right hip joint space, as well as a special face, joint laxity, and slender fingers, which were typical characteristics of SEMDJL1. A gene analysis showed two suspicious mutations in the B3GALT6 gene: c.808G > A(p.(G270S)) and c.942G > C(p.(W314C)), which were verified to be compound heterozygous mutations by analyzing genes in his parents. This mutation was not included in the HGMD, ClinVar, and other mutation databases, and thus was a newly discovered mutation.ConclusionUsing the clinical and genetic analyses, this study reported a Chinese case with EDS-like SEMDJL1 for the first time. Two pathogenic mutations were discovered in the B3GALT6 gene: c.808G > A(p.(G270S)) and c.942G > C(p.(W314C)).

BackgroundShoulder arthroscopic surgery is a common surgical method used in orthopedics. However, severe postoperative pain can significantly limit the early joint movement of patients and adversely affect the impact of the surgery. At present, there is no consistent and effective analgesic scheme for the management of postoperative pain after arthroscopic surgery of the shoulder.PurposeThe aim of this study was to search for the most effective analgesic scheme to control pain in the perioperative period of arthroscopic surgery of the shoulder.Study DesignNetwork meta-analysis.MethodsWe searched 5 different databases (i.e., Medline, PubMed, Embase, Web of Science, and the Cochrane Library) from January 2011 to January 2021 for English literature. Thereafter, we sifted out randomized controlled trials (RCTs), which compared different intervention schemes for pain management after shoulder arthroscopy and selected only 12 h, 24 h, or 48 h after the patient leaves the operating room as an optimal period for administration of analgesic intervention schemes. Only patients with shoulder disease who have undergone arthroscopic shoulder surgery were included in this study. The Cochrane “risk of bias” was used for the quality assessment. Moreover, some additional tests were performed to enhance the credibility of the results.ResultsTwenty-nine RCTs involving 1,885 patients were included in this frequentist network meta-analysis (NMA). These articles mainly were divided into two distinct groups, namely, the nerve block group and the non-nerve block group. Regarding the nerve block group, at postoperative 12 h, the intervention suprascapular nerve block + interscalene nerve block (SSNB + INB) was ranked first, whereas INB + intra-articular injection (INB + IAI) was ranked first at 24 h and 48 h postoperation. In the non-nerve block group, external application (EA) was ranked first at postoperative 12 h, but oral administration (OA) exhibited a better analgesic effect at postoperative 24 h and postoperative 48 h.ConclusionWe conclude that the analgesic effect of SSNB+INB was the best at postoperative 12 h, and INB+IAI was the best at postoperative 24 h and 48 h in the nerve block group. For the non-nerve block group, the effect of EA was the best at postoperative 12 h, and the analgesic effect of OA at postoperative 24 h and 48 h was significantly better than any other interventions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42021286777.

Abstract As one of the basic supporting technologies of 5G system, wireless sensor networks technology is facing a new challenge to improve its transmission energy efficiency. This paper considers combining simultaneous wireless information and power transfer (SWIPT) technique and routing technique, and applying them to multi-hop clustered wireless sensor networks (MCWSN), where each node can decode information and harvest energy from a received radio-frequency signal. And the relay nodes in MCWSN can utilize the harvest energy to forward data to their next hop nodes according to the routing scheme. First, we formulate an energy-efficient routing problem of MCWSN with SWIPT. Then, a heuristic energy efficient cooperative SWIPT routing algorithm (EECSR) is presented to find a transmission path with the maximum energy efficiency. Specifically, in EECSR, the resource allocation problem in each hop of the path is transformed to some equivalent convex optimization problems, which are resolved via dual decomposition. Moreover, a distributed routing protocol based on EECSR is proposed. As far as we know, this is the first solution that considers energy efficiency optimization based on routing and SWIPT in MCWSN. Simulation results show that our EECSR algorithm has high energy efficiency and good robustness. And our distributed routing protocol has better real-time performance than traditional protocols.

Congenital nasolacrimal duct obstruction(CNLDO)has an incidence rate of 5.7% and there are many clinical treatments for the disease. But these treatments have been taken very randomly. Therefore, it is still a controversial topic on how to choose the best treatment. This paper will discuss the treatments of CNLDO so as to know the characteristics of each treatment for better clinical services.

This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 (P

Certificateless strong designated verifier signature schemes have realized the merit of CL-PKC against the traditional strong designated verifier signatures. However, when the signer and the designated verifier disagree with the signature, existing schemes cannot distinguish the original signature from the signature transcript. In addition, errors or malicious actions introduced by the designated verifier may lead to the failure of signature verification. To solve these issues, we propose a certificateless verifiable strong designated verifier signature scheme. When disputes arise between the signer and the verifier, the scheme can effectively prevent the signer from denying the signature generated by the signer, as well as the designated verifier from denying valid signatures or invalid ones. Our scheme does not rely on bilinear pairings. The proposed scheme satisfies the requirements of verifiability, unforgeability, non-delegability, non-transferability and signer ambiguity. We also provide formal security proof in the random oracle model for the proposed scheme.

Alzheimer’s disease (AD) is a neurological disorder characterized by neuronal cell death, tau pathology, and excessive inflammatory responses. Several vascular risk factors contribute to damage of the blood–brain barrier (BBB), secondary leak-out of blood vessels, and infiltration of inflammatory cells, which aggravate the functional disability and pathological changes in AD. Growth factor angiopoietin-1 (Ang-1) can stabilize the endothelium and reduce endothelial permeability by binding to receptor tyrosine kinase 2 (Tie2). C16 peptide (KAFDITYVRLKF) selectively binds to integrin ανβ3 and competitively inhibits leukocyte transmigration into the central nervous system by interfering with leukocyte ligands. In the present study, 45 male Sprague-Dawley (SD) rats were randomly divided into three groups: vehicle group, C16 peptide + Ang1 (C + A) group, and sham control group. The vehicle and C + A groups were subjected to two-vessel occlusion (2-VO) with artery ligation followed by Aβ1-42 injection into the hippocampus. The sham control group underwent sham surgery and injection with an equal amount of phosphate-buffered saline (PBS) instead of Aβ1-42. The C + A group was administered 1 mL of drug containing 2 mg of C16 and 400 µg of Ang-1 daily for 2 weeks. The sham control and vehicle groups were administered 1 mL of PBS for 2 weeks. Our results showed that treatment with Ang-1 plus C16 improved functional disability and reduced neuronal death by inhibiting inflammatory cell infiltration, protecting vascular endothelial cells, and maintaining BBB permeability. The results suggest that these compounds may be potential therapeutic agents for AD and warrant further investigation.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Human serum albumin (HSA) is widely used in the clinic for the treatment of several diseases in large amount each year. With the increasing demands of HSA in clinic and limited blood resource, recombinant HSA (rHSA) is becoming an attractive and alternative source for HSA production. In this study, we aimed to express rHSA in the mammary glands of transgenic mice by using a tissue-specific promoter and other regulatory elements. An rHSA expression vector was constructed bearing the cDNA and first intron of HSA under the control of bovine αs1-casein promoter with a 2 × chicken β-globin insulator in the front. Transgenic mice were generated and reverse transcription polymerase chain reaction showed that rHSA was expressed only in the mammary gland, indicating the tissue specificity of the bovine αs1-casein promoter in directing transgene transcription in transgenic mice. Enzyme-linked immunosorbent assay test showed that rHSA was successfully secreted into the milk of transgenic mice with the highest level at 1.98 ± 0.12 g/L. Our results indicate the ability of the bovine αs1-casein promoter to induce successful expression of rHSA in the mammary gland of transgenic mice.

Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of “anti-inflammatory” T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.

Objective This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60–72 months.Design Cross-sectional.Participants 1342 children with complete data on the questionnaire, stereoacuity and refraction were included.Results The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis.Conclusion Later-borns had poorer stereoacuity than first-borns.

The goal of this study was to elucidate the mechanism of action of C16, a laminin-1 peptide that competes with αvβ3 for integrin binding, in treating neuromyelitis optica (NMO). A NMO rat model was established and specific inhibitors were used to investigate the effect of Tie2 kinase, integrin, and PI3K/Akt signaling pathways on C16 function in NMO using histological, immunohistochemical, immunofluorescence, Western blot, and ELISA assays. A total of 150 rats were divided into five groups: a control untreated group (n = 18) and four test groups (n = 33 per group) including vehicle-treated control, C16, Tie2 kinase inhibitor + C16, and PI3K/Akt inhibitor LY294002 + C16. We found that inhibiting Tie2 kinase resulted in partial loss of C16 peptide-mediated effects, while suppressing PI3K/Akt signaling reduced C16 peptide-mediated effects. In addition, activation of the αvβ3 integrin axis and Tie2 kinase promoted PI3K/Akt signaling. Our study showed that the Tie2-PI3K/Akt, Tie2 integrin, and integrin-PI3K/Akt signaling pathways regulate C16 peptide function in vascular growth and stabilization as well as inflammation in NMO.

Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common human malignant diseases in the world, and the mechanisms underlying HCC carcinogenesis and progression need further investigation. MicroRNAs play important roles in the development of cancer, and miR-500a is suggested to be deregulated in some types of cancer. However, the underlying molecular mechanisms of miR-500a in HCC remain unknown. Methods: The expression of miR-500a in HCC was analyzed in The Cancer Genome Atlas (TCGA) database and examined in 33 pairs of HCC tissues and matched nontumor tissues. The correlation between miR-500a expression and prognosis of HCC patients was analyzed from the survival data in TCGA. The mechanism of miR-500a upregulation in HCC was detected using chromatin immunoprecipitation-quantitative real-time PCR. The roles of miR-500a in HCC development were examined using a cell counting kit-8 assay in vitro and growth of transplanted tumors in nude mice in vivo. Apoptosis of HCC was detected using Annexin V/propidium iodide staining. The expression of BH3-interacting death agonist (BID) protein was examined using western blot analysis. Results: miR-500a expression was upregulated in HCC tissues, and high miR-500a expression was significantly correlated with the poor prognosis of HCC patients. Histone modifications in the promoter region of miR-500a may be responsible for its increased expression. Inhibition of miR-500a in HCC cell lines significantly promoted apoptosis, as well as inhibiting the proliferation of HCC cells and growth of transplanted tumors in nude mice. miR-500a directly targeted the 3′ untranslated region of BID mRNA, and inhibition of miR-500a-promoted apoptosis was almost completely abolished by the administration of ABT-199 via the BID-mitochondria pathway. Conclusion: Our results suggest that histone modifications in the promoter region of miR-500a may be responsible for the increased expression of miR-500a in HCC, which promotes cancer progression by targeting BID, indicating that miR-500a may be a potential prognostic predictor and therapeutic target for HCC patients.

With the development of modern industry and scientific technology, production equipment plays an increasingly important role in military and industrial production, and the fault detection signal of gears and bearings state in transmission equipment becomes very important. Therefore, this paper proposes a gear-bearing composite fault signal decomposition and reconstruction method, which combines the marine predator algorithm (MPA) and variational mode decomposition (VMD) technologies. For the parameters’ selection of VMD, the optimization algorithm allows us to quickly and accurately obtain the results with the best kurtosis correlation index after signal decomposition and reconstruction. The experiments demonstrate the excellent performance of our method in the field of separation and denoising mixed gear-bearing fault signals.

Abstract Background Current immunosuppressive medications used after transplantation induce significant toxicity , and a new medication regimen is needed. Based on recent research, Sirt1 exerts a proinflammatory effect on the immune response. Sirtinol is a Sirt1 inhibitor, but its impact on allograft rejection and its molecular mechanisms of action have not yet been reported. Resluts In this study, we examined the effect of sirtinol on prolonging allograft survival in a mouse cervical heterotopic heart transplantation model. Based on an examination of the allograft, allografts from sirtinol-treated recipients show significantly lower levels of IL-17A expression and higher levels of Foxp3 expression. In vivo, sirtinol reduces the proportion of Th17 cells and increases the proportion of Treg cells in splenocytes from recipients. In vitro, sirtinol reduces the proportion of Th17 cells and decreases the expression of IL-17A and RORγt in an isolated CD4+ T cell population. Moreover, we identified synergistic effects of sirtinol and FK506 on prolonging allograft survival, and sirtinol synergizes with FK506 to promote Foxp3 expression. Conclusion Sirtinol, a Sirt1 inhibitor, may be a promising immunosuppressive drug to prevent the rejection reaction in combination with FK506.

Generative adversarial networks (GANs) have a revolutionary influence on sample generation. Maximum mean discrepancy GANs (MMD-GANs) own competitive performance when compared with other GANs. However, the loss function of MMD-GANs is an empirical estimate of maximum mean discrepancy (MMD) and not precise in measuring the distance between sample distributions, which inhibits MMD-GANs training. We propose an efficient divide-and-conquer model, called DC-MMD-GANs, which constrains the loss function of MMD to tight bound on the deviation between empirical estimate and expected value of MMD and accelerates the training process. DC-MMD-GANs contain a division step and conquer step. In the division step, we learn the embedding of training images based on auto-encoder, and partition the training images into adaptive subsets through k-means clustering based on the embedding. In the conquer step, sub-models are fed with subsets separately and trained synchronously. The loss function values of all sub-models are integrated to compute a new weight-sum loss function. The new loss function with tight deviation bound provides more precise gradients for improving performance. Experimental results show that with a fixed number of iterations, DC-MMD-GANs can converge faster, and achieve better performance compared with the standard MMD-GANs on celebA and CIFAR-10 datasets.

Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease that mainly affects the spinal cord and optic nerve, causing blindness and paralysis in some individuals. Moreover, NMO may cause secondary complement-dependent cytotoxicity (CDC), leading to oligodendrocyte and neuronal damage. In this study, a rodent NMO model, showing typical NMO pathogenesis, was induced with NMO-IgG from patient serum and human complement. We then tested whether the combination of C16, an αvβ3 integrin-binding peptide, and angiopoietin-1 (Ang1), a member of the endothelial growth factor family, could alleviate NMO in the model. Our results demonstrated that this combination therapy significantly decreased disease severity, inflammatory cell infiltration, secondary demyelination, and axonal loss, thus reducing neural death. In conclusion, our study suggests a possible treatment that can relieve progressive blindness and paralysis in an animal model of NMO through improvement of the inflammatory milieu.