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The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC).

Abstract Background CXC chemokine ligand 3 (CXCL3) is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a critical role in mediating tumor development and progression. However, the expression profile of CXCL3 and the exact molecular mechanism behind the role of CXCL3 in colon adenocarcinoma (COAD) has not been fully elucidated. Methods The expression and clinical significance of CXCL3 mRNA and protein in the tissues from COAD patients were estimated using bioinformatics and immunohistochemistry assays. The expression and roles of exogenous administration or overexpression of CXCL3 in HT-29 and SW480 COAD cells were determined using enzyme-linked immunosorbent assay(ELISA), Cell Counting Kit-8 (CCK-8) and Transwell assays. Mechanically, CXCL3-induced malignant behaviors were elucidated using western blotting assay and extracellular signal-regulated protein kinase 1/2 (ERk1/2) inhibitor PD98059. Results The cancer genome atlas (TCGA)-COAD data analysis revealed that CXCL3 mRNA is highly expressed and has high clinical diagnostic accuracy in COAD. Increased expression of CXCL3 mRNA was associated with patient’s clinical stage, race, gender, age, histological subtype, nodal mestastasis and tumor protein 53 (TP53) mutation status. Similarly, immunohistochemistry assay also exhibited that CXCL3 protein in COAD tissues was significantly up-regulated. Gene expression associated assay implied that CXC chemokine ligand 1 (CXCL1) and CXC chemokine ligand 2 (CXCL2) were markedly correlated with CXCL3 in COAD. Protein-protein interaction (PPI) analysis revealed that cyclin B1 (CCNB1), mitotic arrest deficient 2 like 1 (MAD2L1), H2A family member Z (H2AFZ) and CXCL2 may be the important protein molecules involved in CXCL3-related tumor biology. Gene set enrichment analysis (GSEA) analysis revealed that CXCL3 was mainly enriched in the cell cycle, DNA replication, NOD-like receptors, NOTCH and transforming growth factor-β (TGF-β) Signal pathways. In vitro, exogenous administration or overexpression of CXCL3 resulted in increased malignant behaviors of HT-29 and SW480 cells, and down-regulation of CXCL3 expression inhibited the malignant behaviors of these tumor cells. In addition, overexpression of CXCL3 affected the expression of genes related to extracellular signal regulated kinase (ERK) pathway, including ERK1/2, p-ERK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cyclin D1. Finally, CXCL3-induced malignant behaviors in HT-29 and SW480 cells were obviously attenuated following treatment with ERK inhibitor PD98059. Conclusion CXCL3 is upregulated in COAD and plays a crucial role in the control of malignant behaviors of tumor cells, which indicated its involvement in the pathogenesis of COAD.

Beam pumping is currently the broadly used method for oil extraction worldwide. A pumpjack shutdown can be incurred by failures from the load, corrosion, work intensity, and downhole working environment. In this study, the duration of uninterrupted pumpjack operation is defined as the pump inspection cycle. Accurate prediction of the pump inspection cycle can extend the lifespan, reduce unexpected pump accidents, and significantly enhance the production efficiency of the pumpjack. To enhance the prediction performance, this study proposes an improved two-layer stacking ensemble model, which combines the power of the random forests, light gradient boosting machine, support vector regression, and Adaptive Boosting approaches, for predicting the pump inspection cycle. A big pump-related oilfield data set is used to demonstrate the proposed two-layer stacking ensemble model can significantly enhance the prediction quality of the pump inspection cycle.

Calcium plays a crucial role in plant growth and development, yet little is known about its function in endodormancy regulation. Tree peony (Paeonia suffruticosa), characterized by compound buds and large flowers, is well-known for its ornamental and medicinal value. To break bud dormancy release is a prerequisite of flowering and forcing culture, particularly during the Spring Festival. In this study, the Ca2+ chelator EGTA and Ca2+ channel blocker LaCl3 were applied, resulting in a significant delay in budburst during both chilling- and gibberellin (GA)- induced dormancy release in a dosage-dependent manner. As expected, the retardation of bud break was recovered by the supplementation of 30 mM CaCl2, indicating a facilitating role of calcium in dormancy release. Accordingly, several calcium-sensor-encoding genes including Calmodulin (CaM) and Ca2+-dependent protein kinases (CDPKs) were significantly up-regulated by prolonged chilling and exogenous GAs. Ultrastructure observations revealed a decline in starch grains and the reopening of transport corridors following prolonged chilling. Calcium deposits were abundant in the cell walls and intercellular spaces at the early dormant stage but were enriched in the cytosol and nucleus before dormancy release. Additionally, several genes associated with dormancy release, including EBB1, EBB3, SVP, GA20ox, RGL1, BG6, and BG9, were differentially expressed after calcium blocking and recovery treatments, indicating that calcium might partially modulate dormancy release through GA and ABA pathways. Our findings provide novel insights into the mechanism of dormancy release and offer potential benefits for improving and perfecting forcing culture technology in tree peonies.

The bias of the maximum likelihood estimator can cause a considerable estimation error if the sample size is small. To reduce the bias of the maximum likelihood estimator under the small sample situation, the maximum likelihood and parametric bootstrap bias-correction methods are proposed in this study to obtain more reliable maximum likelihood estimators of the unit exponential distribution parameters. The procedure to implement the bias-corrected maximum likelihood estimation method is derived analytically, and the steps to obtain the bias-corrected bootstrap estimators are presented. The simulation results show that the proposed maximum likelihood bootstrap bias-correction method can significantly reduce the bias and mean squared error of the maximum likelihood estimators for most of the parameter combinations in the simulation study. A soil moisture data set and a numerical example are used for illustration.

A new inorganic flame retardant P/N-GO was prepared by chemically modifying graphene oxide (GO) with phosphorus trichloride (POCl3) and 4,4-diamino-diphenylmethane (DDM). The P/N-GO was covalently grafted into a phosphorus-containing aqueous polyurethane (PWPU) system to prepare a flame-retardant nanocomposite (P/N-GO/PWPU). Due to the uniform distribution of P/N-GO in the polymer matrix, a strong interfacial adhesion can be formed and the mechanical properties of the WPU can be significantly improved. The mechanical strength of the composites increased from 4.56 MPa to 9.16 MPa. The LOI value of WPU increased from 25.5% to 30.5%, indicating that its flame-retardant properties were improved and met the standards for flame-retardant materials. At the same time, the peak heat release rate (PHRR) was reduced from 184.374 kW/m2 to 116.730 kW/m2, which showed good flame retardant properties of P/N-GO/PWPU and was favourable for expanding the application scope and safe use of WPU.

Infectious diseases are severe public health events that threaten global health. Prophylactic vaccines have been considered as the most effective strategy to train the immune system to recognize and clear pathogenic infections. However, the existing vaccines against infectious diseases have several limitations, such as difficulties in mass manufacturing and storage, weak immunogenicity, and low efficiency of available adjuvants. Biomaterials, especially functional polymers, are expected to break through these bottlenecks based on the advantages of biocompatibility, degradability, controlled synthesis, easy modification, precise targeting, and immune modulation, which are excellent carriers and adjuvants of vaccines. This review mainly summarizes the application of immunologically effective polymers-enhanced vaccines against viruses- and bacteria-related infectious diseases and predicted their potential improvements.

The standardized nutrition support therapy can improve the nutritional status, immunity, quality of life, and clinical outcomes of patients with novel coronavirus disease (COVID-19) infection. The latest Chinese government policy also clearly states that nutrition support therapy should be included in the whole process of treatment and recovery of patients with COVID-19. Therefore, the Beijing Quality Control and Improvement Center for Clinical Nutrition Therapy has organized relevant experts to formulate the Recommendations of Nutritional Treatment for Patients with COVID-19 Infection (2023), following the latest clinical nutrition guidelines, research evidence and clinical practice of nutrition support of COVID-19. The recommendations suggest that individualized nutrition management be implemented by following the standardized pathway of nutrition management, which includes nutrition-risk screening, malnutrition diagnosis, nutrition treatment and nutrition monitoring, and by taking into account the clinical characteristics of patients with COVID-19.

BackgroundThe purpose of this study was to evaluate the changes in fundus vascular density and micromorphological structure of all vascular plexuses during the different stages of diabetic retinopathy (DR), and the correlation between fundus blood flow and the DR severity.MethodsThis observational cross-sectional study was conducted of 50 eyes with different stages of DR, 25 diabetes mellitus (DM) patients without clinical signs of DR and 41 healthy eyes. The foveal avascular zone (FAZ), vessel density of superficial capillary plexus (SCP), and deep retinal capillary plexus (DCP) were acquired by RTVue XR Avanti OCTA device. The perfusion density (PD), skeleton vessel density (SVD) was manually calculated using ImageJ. The area under receiver operating characteristic (ROC) curve was used to determine the diagnostic value of OCTA parameters in distinguishing DR and healthy eyes.ResultsThe choroidal VD were significantly higher in the healthy group than in the DM without DR, NPDR, and PDR groups (p

In this study, the estimation methods of bias-corrected maximum likelihood (BCML), bootstrap BCML (B-BCML) and Bayesian using Jeffrey’s prior distribution were proposed for the inverse Gaussian distribution with small sample cases to obtain the ML and Bayes estimators of the model parameters and the process performance index based on the lower specification process performance index. Moreover, an approximate confidence interval and the highest posterior density interval of the process performance index were established via the delta and Bayesian inference methods, respectively. To overcome the computational difficulty of sampling from the posterior distribution in Bayesian inference, the Markov chain Monte Carlo approach was used to implement the proposed Bayesian inference procedures. Monte Carlo simulations were conducted to evaluate the performance of the proposed BCML, B-BCML and Bayesian estimation methods. An example of the active repair times for an airborne communication transceiver is used for illustration.

Cervical spinal fusion is the standard of care for treating intractable spinal diseases. However, frequent adjacent segment disease (ASD) has recently drawn a great deal of attention among clinicians and researchers. At present, the etiology of ASD remains controversial. The investigation of cervical spine biomechanics after fusion may contribute to understanding the causes of ASD. In the present study, a cervical spinal musculoskeletal fusion model, with multi-body dynamics method, was established. Dynamic head flexion–extension movements were simulated for both a fusion subject and a normal subject. The cervical spinal loading pattern, load sharing ratios, and translations of instant centers of the rotation at adjacent segments were then predicted. The average intervertebral compressive forces, shear forces, and facet joint forces against the intervertebral angle were also obtained. By comparison, some obvious differences in cervical spinal loading patterns were found between the fusion subject and the normal subject. Fusion surgery would alter the postoperative biomechanical surrounding of the cervical spine, especially the adjacent segments. These changes might affect the intervertebral disc-bearing capacity, and even weaken the physiological structure. From a purely biomechanical perspective, the cervical spinal fusion model can contribute to comprehending the etiology of ASD after spinal fusion.

Abstract Excessive wear is a key issue affecting the performance of ultra‐high molecular weight polyethylene (UHMWPE)‐based artificial prosthesis. This work is focussed on the bio‐tribology behaviours of UHMWPE when mating with different metal counterparts (iron‐based 316L, Co‐based Stellite‐S21 and Stellite‐S22). According to the ASTM F732 standard, two million cycles comparative wear tests were carried out under bovine serum lubrication. When coupled with S21, S22, and 316L metal counterparts, the obtained average wear factors of UHMWPE were 1.333 ± 0.192, 1.360 ± 0.160, and 1.190 ± 0.177 × 10−6 mm3/N · m, respectively. Initial surface roughness of the metal counterpart has shown an important role in controlling the volume of UHMWPE wear, especially the first one million cycles. Compared with 316L, CoCrMo‐based counterparts possessed relative higher hardness and exhibited less rise in surface roughness caused by wear. For UHMWPE‐on‐metal bearings, random scratch, surface pit, and wear debris attachment were commonly seen, which suggested the coexistence of abrasion, third‐body abrasion, and adhesion‐based wear. In contrast, the metal counterpart was slightly scratched with no polymer transfer film formation. The work conducted in the present study gives useful knowledge regarding the UHMWPE‐on‐metal bearing design. With an intention to minimise wear, surface roughness of metal counterpart should be carefully controlled.

Objective: To determine whether sildenafil has an effect on pregnancy outcomes in patients with poor endometrial development. Methods: This study included 472 infertility patients who underwent in vitro fertilization/intracytoplasmatic sperm injection and frozen-thawed embryo transfer (IVF/ICSI-FET) and subsequently suffered from poor endometrial development during hormone replacement cycle (HRC) from April 2017 to July 2019. The patients were divided into two groups: the sildenafil group (n ​= ​88) and the control group (n ​= ​384). We analyzed endometrial thicknesses and types on endometrial transformation day, as well as pregnancy outcomes after FET (biochemical pregnancy, clinical pregnancy, early abortion, late abortion, and live birth rates) between the two groups. Results: After adjusting for confounding factors, we found no significant differences in endometrial thicknesses and types on endometrial transformation day between the sildenafil group and the control group (0.79 ​± ​0.08 vs 0.81 ​± ​0.09, P ​= ​0.144; 79.76% vs83.87%, P ​= ​0.402). There were also no statistically significant differences in biochemical pregnancy rate (75.0% vs 76.8%, P ​= ​0.892), clinical pregnancy rate (59.09% vs 69.53%, P ​= ​0.087), early abortion rate (17.31% vs 14.61%, P ​= ​0.557), late abortion rate (3.85% vs 4.49%, P ​= ​0.859), or live birth rate (45.45% vs 55.47%, P ​= ​0.101) between the two groups. In subgroup analysis, the application of sildenafil was unable to improve endometrial thickness (group one: 0.80 ​± ​0.08 ​cm vs 0.82 ​± ​0.08 ​cm; group two:0.78 ​± ​0.08 ​cm vs 0.80 ​± ​0.10 ​cm; group three:0.75 ​± ​0.11 ​cm vs 0.77 ​± ​0.08 ​cm, p ​> ​0.05) and type endometrium on transformation day (group one: 78.57% vs 86.78%; group two: 80.65% vs 77.78%; group three: 81.82% vs 83.78%, p ​> ​0.05). Moreover, sildenafil use was not closely associated with clinical pregnancy outcomes, clinical pregnancy rate, early abortion rate, late abortion rate, and live birth rate (p ​> ​0.05). Conclusions: Sildenafil did not benefit endometrial development and pregnancy outcomes in patients with poor endometrial development during the hormone replacement cycle.

The MoO3–Bi2O3 binary oxides with higher ion potential difference, lower interaction parameters and lower melting points were selected as the high temperature lubricants for NiAl-based coating to further improve the tribological properties in wide temperature range. The friction and wear performance at low and medium temperatures (400–600 °C) is significantly improved compared to previous works. The NiAl-nanostructured MoO3/Bi2O3 composite coatings were fabricated via atmospheric plasma spraying (APS). The impact of the ratio of the MoO3/Bi2O3 binary oxides on the mechanical and tribological properties at high temperatures was investigated. The results show that the friction coefficients and wear rates of composite coating with a MoO3:Bi2O3 ratio of 1:1 were significantly reduced from room temperature to 800 °C compare with our previous work, where, the friction coefficient and wear rate were reduced to lower than 0.22 and 2.8 × 10−5 mm3·(N·m)-1 at 400–800 °C. The decrease of friction coefficient at room temperature is due to the lower melting points of MoO3 and Bi2O3 than that of other oxides. While above 400 °C, the improved friction and wear performance was attributed to the formation of new easy-to-shear ternary oxides as NiMoO4, Bi2Mo3O12 and Bi2MoO6 on the worn surfaces through tribo–chemical reactions, which works synergistically to reduce the friction coefficients and wear rate.

Abstract In this study, the effects of in vivo (head flexion‐extension, lateral bending, and axial rotation) and in vitro (ISO 18192‐1) working conditions on the wear of ultrahigh molecular weight polyethylene (UHWMPE)‐based cervical disc prosthesis were studied via numerical simulation. A finite‐element‐based wear prediction framework was built by using a sliding distance and contact area dependent Archard wear law. Moreover, a pre‐developed cervical spine multi‐body dynamics model was incorporated to obtain the in vivo conditions. Contact mechanic analysis stated that in vitro conditions normally led to a higher contact stress and a longer sliding distance, with oval or crossing‐path‐typed sliding track. In contrast, in vivo conditions led to a curvilinear‐typed sliding track. In general, the predicted in vivo wear rate was one order of magnitude smaller than that of in vitro. According to the yearly occurrence of head movement, the estimated total in vivo wear rate was 0.595 mg/annual. While, the wear rate given by the ISO standard test condition was 3.32 mg/annual. There is a significant impact of loading and kinematic condition on the wear of UHMWPE prosthesis. The work conducted in the present study provided a feasible way for quantitatively assessing the wear of joint prosthesis.

Immunotherapy has paved the way for the future of cancer therapy, but there are still significant challenges to be overcome, such as the occurrence of immune escape or suppression. Adenosine is essential in modulating the immune responses of immune cells and maintaining immune tolerance. Emerging adenosine pathway inhibitors are considered a breakthrough in cancer immunotherapy, with emphasis first being placed on the top-down blockade of adenosine signaling axis, followed by combination therapy. However, these therapeutic strategies rely on adenosine inhibitors, mainly small molecules or antibody proteins, which are limited by a single route of administration and off-target toxicity. Therefore, synergistic nanomedicine with accurate delivery targeting deeper tumors is focused on in preclinical studies. This review discusses how adenosine reshapes immunosuppressive microenvironments through its effects on immune cells, including lymphocytes and myeloid cells. Additionally, it will be the first discussion of a comprehensive strategy of biomaterials in modulating the adenosine signaling pathway, including inhibition of adenosine production, inhibition of adenosine binding to immune cells, and depletion of adenosine in the microenvironments. Furthermore, biomaterials integrating multiple therapeutic modalities with adenosine blocking are also discussed as a promising strategy for promoting cancer immunotherapy.

Portable devices possess powerful application prospects in on-site sensing without the limitation of bulky instruments. Given the relevance of pesticides to food safety, we herein fabricated a robust gold nanocluster (AuNC)-based hydrogel test kit for precisely quantified chlorpyrifos by using a three-dimensional (3D) printed subsidiary device. In this work, the fluorescence of AuNC-based hydrogel could be efficiently quenched by cobalt oxyhydroxide nanoflakes (CoOOH NFs) through the Förster resonance energy transfer effect. Chlorpyrifos as an acetylcholinesterase inhibitor controls the enzymatic hydrolysis reaction and further regulates the production of thiocholine that could decompose CoOOH nanoflakes into Co2+, resulting in the fluorescence response of AuNC-based hydrogel. By using a homemade subsidiary device and smartphone, the fluorescence color was transformed into digital information, achieving the on-site quantitative detection of chlorpyrifos with the limit of detection of 0.59 ng ml−1. Owing to specific AuNC signatures and hydrogel encapsulation, the proposed fluorescence hydrogel test kit displayed high sensitivity, good selectivity, and anti-interference capability in a real sample analysis, providing great potential in on-site applications.

The performance and programming conditions of the triple shape memory of crosslinked trans-polyisoprene/poly (ethylene-co-vinyl acetate) (TPI/EVA) composites with different contents of dicumyl peroxide (DCP) were investigated. The effect of triple shape memory in the TPI/EVA composites was studied by tensile loading, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and dynamic thermomechanical analysis (DMA). It was demonstrated that the content of DCP increased, the crystallization temperature of TPI decreased from 55.2 to 38.3 °C, and the crystallization temperature of EVA decreased slightly. The SEM results showed that DCP, as an initiator, could form a graft copolymer of TPI-g-EVA at the interface of the two phases, which could improve the adhesion of the two phases. The DMA showed that the higher the content of DCP, the higher the first-stage shape recovery ratio. Moreover, the composites exhibited favorable shape fixity ratio (Rf) and shape recovery ratio (Rr) with the incorporation of 0.4 phr DCP. At the same time, it was demonstrated that the TPI/EVA composites showed excellent mechanical strength, including tensile strength up to 24.3 MPa, as well as elongation at break reaching 508%.

Glioma is the most common primary craniocerebral malignant tumor, arising from the canceration of glial cells in the brain and spinal cord. The quality of life and prognosis of patients with this disease are still poor. Doxorubicin (DOX) is one of the most traditional and economical chemotherapeutic drugs for the treatment of glioma, but its toxic effect on normal cells and the resistance of tumor cells to DOX make the application of DOX in the treatment of glioma gradually less effective. To solve this problem, we co-encapsulated DOX and endogenous tumor suppressor miR-125b into nanoparticles (NPs) by nanoprecipitation methods, and passively targeted them into glioma cells. In vitro experiments show that miR-125b and DOX can be effectively encapsulated into nanoparticles with different ratios, and by targeting YES proto-oncogene 1 (YES1), they can affect the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/p53 pathway and induce brain glioma cell apoptosis. They can also affect the DNA damage repair process and inhibit cell proliferation. The obtained data suggest that co-delivery of DOX and miR-125b could achieve synergistic effects on tumor suppression. Nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

Over the years, lung cancer remains the leading cause of cancer deaths in worldwide. In view of this, increasingly importance has been attached to the further optimization and improvement of its treatment. Reactive oxygen species (ROS) play a key role in regulating tumor development and anti-cancer treatment. Recently, the development of nanomaterials provides new platforms for ROS-based cancer treatment methods, which can help to reduce side effects and enhance anti-cancer effects. In recent years, a variety of lung cancer treatment models have been reported, such as chemodynamic therapy (CDT), photodynamic therapy (PDT), radiation therapy (RT) and controlled drug release (CDR). In this review, we are going to discuss the possible mechanism of action and current research status of ROS-based nanomaterials in the treatment of lung cancer in order to provide constructive ideas for relative research and expect this work could inspire the future development of novel lung cancer treatments.

The process performance index (PPI) can be a simple metric to connect the conforming rate of products. The properties of the PPI have been well studied for the normal distribution and other widely used lifetime distributions, such as the Weibull, Gamma, and Pareto distributions. Assume that the quality characteristic of product follows power-normal distribution. Statistical inference procedures for the PPI are established. The maximum likelihood estimation method for the model parameters and PPI is investigated and the exact Fisher information matrix is derived. We discuss the drawbacks of using the exact Fisher information matrix to obtain the confidence interval of the model parameters. The parametric bootstrap percentile and bootstrap bias-corrected percentile methods are proposed to obtain approximate confidence intervals for the model parameters and PPI. Monte Carlo simulations are conducted to evaluate the performance of the proposed methods. One example about the flow width of the resist in the hard-bake process is used for illustration.

Additive manufacturing provides a novel and robust way to prepare medical product with anatomic matched geometry and tailored mechanical performance. In this study, the surface characteristics, microstructure, and mechanical properties of fused deposition modeling (FDM) prepared polyether-ether-ketone (PEEK) were systematically studied. During the FDM process, the crystal unit cell and thermal attribute of PEEK material remained unchanged, whereas the surface layer generally became more hydrophilic with an obvious reduction in surface hardness. Raster angle has a significant effect on the mechanical strength but not on the failure mechanism. In practice, FDM fabricated PEEK acted more like a laminate rather than a unified structure. Its main failure mechanism was correlated to the internal voids. The results show that horizontal infill orientation with 30° raster angle is promising for a better comprehensive mechanical performance, and the corresponding tensile, flexural, and shear strengths are (76.5 ± 1.4) MPa, (149.7 ± 3.0) MPa, and (55.5 ± 1.8) MPa, respectively. The findings of this study provide guidelines for FDM-PEEK to enable its realization in applications such as orthopedic implants.

In this study, a new three-statement randomized response estimation method is proposed to improve the drawback that the maximum likelihood estimation method could generate a negative value to estimate the sensitive-nature proportion (SNP) when its true value is small. The Bayes estimator of the SNP is obtained via using a hierarchical Bayesian modeling procedure. Moreover, a hybrid algorithm using Gibbs sampling in Metropolis–Hastings algorithms is used to obtain the Bayes estimator of the SNP. The highest posterior density interval of the SNP is obtained based on the empirical distribution of Markov chains. We use the term 3RR-HB to denote the proposed method here. Monte Carlo simulations show that the quality of 3RR-HB procedure is good and that it can improve the drawback of the maximum likelihood estimation method. The proposed 3RR-HB procedure is simple for use. An example regarding the homosexual proportion of college freshmen is used for illustration.

Considering the impact of the heterogeneous conditions of the mixture baseline distribution on the parameter estimation of a composite dynamical system (CDS), we propose an approach to infer the model parameters and baseline survival function of CDS using the maximum likelihood estimation and Bayesian estimation methods. The power-trend hazard rate function and Burr type XII mixture distribution as the baseline distribution are used to characterize the changes of the residual lifetime distribution of surviving components. The Markov chain Monte Carlo approach via using a new Metropolis–Hastings within the Gibbs sampling algorithm is proposed to overcome the computation complexity when obtaining the Bayes estimates of model parameters. A numerical example is generated from the proposed CDS to analyze the proposed procedure. Monte Carlo simulations are conducted to investigate the performance of the proposed methods, and results show that the proposed Bayesian estimation method outperforms the maximum likelihood estimation method to obtain reliable estimates of the model parameters and baseline survival function in terms of the bias and mean square error.

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg−1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

Background. The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods. After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results. There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions. Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.

A composite dynamic system (CDS) is composed of multiple components. Each component failure can equally induce higher loading on the surviving components and, hence, enhances the hazard rate of each surviving component. The applications of CDS and the reliability evaluation of CDS has earned more attention in the recent two decades. Because the lifetime quality of components could be inconsistent, the lifetimes of components in the CDS is considered to follow heterogeneous baseline Gompertz distributions in this study. A power-trend hazard rate function is used in order to characterize the hazard rate of the CDS. In order to overcome the difficulty of obtaining reliable estimates of the parameters in the CDS model, the Bayesian estimation method utilizing a hybrid Gibbs sampling and Metropolis-Hasting algorithm to implement the Markov chain Monte Carlo approach is proposed for obtaining the Bayes estimators of the CDS parameters. An intensive simulation study is carried out to evaluate the performance of the proposed estimation method. The simulation results show that the proposed estimation method is reliable in providing reliability evaluation information for the CDS. An example regarding the service system of small electric carts is used for illustration.

In this study, two new integrated control charts, named T2-MAE chart and MS-MAE chart, are introduced for monitoring the quality of a process when the mathematical form of nonlinear profile model for quality measure is complicated and unable to be specified. The T2-MAE chart is composed of two memoryless-type control charts and the MS-MAE chart is composed of one memory-type and one memoryless-type control charts. The normality assumption of error terms in the nonlinear profile model for both proposed control charts are extended to a generalized model. An intensive simulation study is conducted to evaluate the performance of the T2-MAE and MS-MAE charts. Simulation results show that the MS-MAE chart outperforms the T2-MAE chart with less false alarms during the Phase I monitoring. Moreover, the MS-MAE chart is sensitive to different shifts on the model parameters and profile shape during the Phase II monitoring. An example about the vertical density profile is used for illustration.

The Burr type XII (BurrXII) distribution is very flexible for modeling and has earned much attention in the past few decades. In this study, the maximum likelihood estimation method and two Bayesian estimation procedures are investigated based on constant-stress accelerated life test (ALT) samples, which are obtained from the doubly truncated three-parameter BurrXII distribution. Because computational difficulty occurs for maximum likelihood estimation method, two Bayesian procedures are suggested to estimate model parameters and lifetime quantiles under the normal use condition. A Markov Chain Monte Carlo approach using the Metropolis−Hastings algorithm via Gibbs sampling is built to obtain Bayes estimators of the model parameters and to construct credible intervals. The proposed Bayesian estimation procedures are simple for practical use, and the obtained Bayes estimates are reliable for evaluating the reliability of lifetime products based on ALT samples. Monte Carlo simulations were conducted to evaluate the performance of these two Bayesian estimation procedures. Simulation results show that the second Bayesian estimation procedure outperforms the first Bayesian estimation procedure in terms of bias and mean squared error when users do not have sufficient knowledge to set up hyperparameters in the prior distributions. Finally, a numerical example about oil-well pumps is used for illustration.

Fetal alcohol spectrum disorder (FASD) can cause severe mental retardation in children who are prenatally exposed to ethanol. The effects of prenatal and early postnatal ethanol exposure on adult hippocampal neurogenesis have been investigated; however, the effects of prenatal ethanol exposure on the subventricular zone (SVZ) have not. Gypenosides (GPs) have been reported to have neuroprotective effects in addition to other bioactivities. The effects of GPs on neural stem cells (NSCs) in the FASD model are unknown. Here, we test the effect of prenatal ethanol exposure on the neonatal SVZ, and the protection potential of GPs on NSCs in FASD rats. Our results show that prenatal ethanol exposure can suppress the cell proliferation and differentiation of neural stem cells in the neonatal SVZ and that GPs (400 mg/kg/day) can significantly increase the cell proliferation and differentiation of neural stem cells inhibited by ethanol. Our data indicate that GPs have neuroprotective effects on the NSCs and can enhance the neurogenesis inhibited by ethanol within the SVZ of neonatal rats. These findings provide new evidence for a potential therapy involving GPs for the treatment of FASD.

This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 101, 102, 103 nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Müller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated.

In-situ printing is a promising injury repair technique that can be directly applied during surgical operations. This paper features a potential in-situ printing platform based on a small-scale robotic arm with a micro-sized dispenser valve. A double-light-source curing method was applied to print poly(ethylene glycol) diacrylate (PEGDA) with a 20% (weight/volume) ratio and the entire process was controlled automatically by a computer interface where droplet diameter, curing time, mechanical properties were measured and essential printing parameters (e.g., nozzle velocity, nozzle frequency) were determined. Three different two-dimensional (2D) plane models (namely, square, circular, and heart-shaped) were printed during initial printing trials. The feasibility study of in-situ printing on curved surfaces was tested using a three-dimensional (3D) printed defect model. The defect was successfully filled using both parallel and ring printing paths. In conclusion, the robotic arm printing platform and its forming method can achieve a rapid curing of PEGDA hydrogel on a curved surface and has the potential to be applied to in-situ printing.