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Abstract The main purpose of this paper is to consider the multiple birth properties for multi-type Markov branching processes. We first construct a new multi-dimensional Markov process based on the multi-type Markov branching process, which can reveal the multiple birth characteristics. Then the joint probability distribution of multiple birth of multi-type Markov branching process until any time t is obtained by using the new process. Furthermore, the probability distribution of multiple birth until the extinction of the process is also given.

The H9N2 subtype of avian influenza virus (AIV) is widely prevalent in poultry and wild birds globally, and has become the predominant subtype circulating in poultry in China. The H9N2 AIV can directly or indirectly (by serving as a “donor virus”) infect humans, posing a significant threat to public health. Currently, there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province, central China. In this study, we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province, and genetic analysis revealed that these viruses belonged to 7 different genotypes. Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations, and exhibited diverse replication abilities within these birds. These viruses could replicate efficiently in the lungs of mice, with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys. At the cellular level, the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays, revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level. The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters. Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China. It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

IntroductionEarly oral feeding (EOF) has been shown to improve postoperative recovery for many surgeries. However, surgeons are still skeptical about EOF after gastric cancer surgery due to possible side effects. This updated systematic review and meta-analysis aimed to investigate the efficacy and safety of EOF in patients after gastric cancer surgery.MethodsRandomized controlled trials (RCTs) investigating EOF in patients after gastric cancer surgery were searched in the databases of PubMed, Embase, Clinicaltrials.gov, and Cochrane from 2005 to 2023, and an updated meta-analysis was performed using RevMan 5.4 software.ResultsThe results of 11 RCTs involving 1,352 patients were included and scrutinized in this analysis. Hospital days [weighted mean difference (WMD), −1.72; 95% confidence interval (CI), −2.14 to −1.30; p

Skeletal muscle aging in rats is a reduction in skeletal muscle mass caused by a decrease in the number or volume of skeletal muscle myofibers. Apoptosis has been recognized to play a key role in accelerating the process of skeletal muscle aging in rats. The thioredoxin (Trx) system is a widely expressed oxidoreductase system that controls the cellular reduction/oxidation state and has both potent anti-free radical damage and important pro-growth and apoptosis inhibitory functions. Previous studies have shown that exercise delays skeletal muscle aging. However, it is unclear whether exercise attenuates skeletal muscle aging via the Trx system. Therefore, the present study used the Trx system as an entry point to explore the effect of aerobic exercise to improve skeletal muscle aging in rats and its possible mechanisms, and to provide a theoretical basis for exercise to delay skeletal muscle aging in rats. It was shown that aerobic exercise in senescent rats resulted in increased gastrocnemius index, decreased body weight, increased endurance, decreased skeletal muscle cell apoptosis, increased activity and protein expression of the Trx system, and decreased expression of p38 and ASK1. Based on these findings, we conclude that 10 weeks of aerobic exercise may enhance the anti-apoptotic effect of Trx by up-regulating Trx and Trx reductase (TR) protein expression, which in turn increases Trx activity in rat skeletal muscle, and ultimately alleviates apoptosis in senescent skeletal muscle cells.

Charcot arthropathy is a rare disease in clinic, which is easy to be misdiagnosed and delayed diagnosis. Imaging examination plays a key role in the diagnosis of Charcot arthropathy. It is important to improve the early diagnosis rate and strive for early treatment to improve the quality of life of these patients. Here we reported a rare case of charcot knee (CK) accompanied by tethered cord syndrome and lumbosacral fur sinus, who presented with joint destruction, joint deformity and multiple free bodies and received joint free bodies removal and joint replacement surgery with acceptable short and midterm follow-up results.

Abstract Background To observe morphologic and functional changes in meibomian glands in pediatric patients with and without lower eyelid epiblepharon. Methods In this prospective observation study, 55 eyes of 55 patients( 24 males, 31 females; mean age ± SD,9.82 ± 2.59 years; range 6–14 years) and 60 eyes of 60 controls ( 32 males, 28 females; mean age ± SD,10.57 ± 2.75 years; range 6–14 years) were included. The following tests were performed: eyelid margin abnormality by slit-lamp examination, measurement of noninvasive keratographic break-up time (NIKBUT), grading of absence of meibomian gland (meibography score) assessed with noncontact meibography, morphologic changes of meibomian glands (thinning, dilatation and distortion), tear production by the Schirmer 1 test, and grading of meibum quality and meibomian gland expressibility. Results The morphologic changes in meibomian glands were more common in the epiblepharon group (56.36%) than in the control group (28.33%) (p = 0.002). The meibum quality was worse in the epiblepharon group than in the control group (p = 0.009), and the NIKBUT was significantly shorter in the epiblepharon group than in the control group (p = 0.012). There was no significant difference in the Schirmer 1 test, meibomian gland expressibility, eyelid margin abnormality score or total meibography score between the two groups. Morphologic changes in the meibomian glands in the upper eyelids (38.18%) were more common than those in the lower eyelids (20%) (p = 0.036) in the epiblepharon group, and the meibography score was higher in the upper eyelids than in the lower eyelids (p = 0.001). Conclusion There are morphological and functional changes in meibomian glands in pediatric patients with lower eyelid epiblepharon. Although the inverted eyelashes were located in the lower eyelid, morphological changes in the meibomian glands were more common in the upper eyelid.

Abstract In this paper, we consider n-type Markov branching–immigration processes. The uniqueness criterion is first established. Then, we construct a related system of differential equations based on the branching property. Furthermore, the explicit expression of extinction probability and the mean extinction time are successfully obtained in the absorbing case by using the unique solution of the related system of differential equations and Kolmogorov forward equations. Finally, the recurrence and ergodicity criteria are given if the zero state 0 is not absorbing.

Abstract This study was designed to explore the expression changes of P2Y1 receptors in the distal colonic myenteric layer of rats. An opioid induced constipation(OIC) rat model was generated by intraperitoneal (i.p) injection of loperamide. At 7 days post-treatment, the model rats were assessed by calculating the fecal water content and the gastrointestinal transit ratio. The immunofluorescence (IF)-based histochemical study was used to observe the distribution of P2Y1 receptors in the distal colonic myenteric plexus. Western blotting (WB) was performed to evaluate the expression changes of P2Y1 proteins in the myenteric layer, and the electrophysiological approaches were carried out to determine the regulatory roles of P2Y1 receptors on distal colonic motor function. IF showed that P2Y1 receptors are co-expressed MOR in the enteric nerve cells of the distal colonic myenteric plexus. Moreover, the WB revealed that the protein levels of P2Y1 were significantly decreased in the distal colonic myenteric layer of OIC rats. In vitro tension experiments exhibited that the P2Y1 receptor antagonist MRS2500 enhanced the spontaneous contraction amplitude, adding EM2 and β-FNA did not have any effect on MRS2500. Therefore, P2Y1 receptor expression could be associated with the occurrence of OIC in this rat model and the regulation of colonic motility by MOR may be related to the release of purine neurotransmitters such as ATP in the colonic nervous system.

An insightful understanding of the formation mechanism of process-inherent defects and deformation is increasingly important for the property evaluation and structural design of ceramic matrix composites (CMCs). For this purpose, a coupled thermal–diffusive–mechanical modeling approach was proposed by considering three important phenomena that occur during the pyrolysis process for manufacturing CMCs: variations of the physical and mechanical properties of the constituents, generation and diffusive of pyrolysis gas, and multiple thermal deformations. The synergistic effects of these three phenomena on the stress, damage development, microstructural morphology, and process deformation of SiC matrix composites were investigated using finite-element simulations. This new approach was validated by comparing the simulation and experimental results. Significant volume shrinkage of the matrix during the polymer-to-ceramic transformation resulted in large tensile stresses and subsequent highly fragmented microstructure in CMCs. The pyrolysis-gas-induced expansion on the matrix under a damage state may yield a positive process deformation of CMCs at the macroscale, overcoming the effects of the volume shrinkage of the bulk matrix at the microscale. The modeling approach is expected to guide high-quality manufacturing of CMCs and comprehensive studies of structure–processing–property relationships.

Pigeon Newcastle disease, caused by pigeon paramyxovirus type 1 (PPMV-1), is a significant infectious disease in pigeons that can result in substantial mortality and poses a severe threat to the pigeon industry. The rapid and accurate onsite diagnosis of pigeon disease is crucial for timely diagnosis and the implementation of effective prevention and control measures. In this study, we established a rapid detection method for PPMV-1 based on recombinase-aided amplification (RAA) and CRISPR/Cas12a. The RAA primers target the conserved regions of the L gene for preamplification in clinical nucleic acid samples, followed by CRISPR/Cas12a detection of the target gene. Visualization could be achieved by combination with a lateral flow dipstick (LFD). This method demonstrated high specificity, showing no cross-reactivity with non-PPMV-1 samples. The sensitivity of the method assessed by fluorescence analysis reached 100 copies/µL, and when it was combined with an LFD, the sensitivity was 103 copies/µL. The constructed RAA-CRISPR/Cas12a-LFD visual detection method was applied to clinical sample testing and was found to enable the rapid and accurate detection of swab samples and tissue specimens. Its sensitivity was consistent with the current gold standard, quantitative real-time PCR results. The RAA-CRISPR/Cas12a-LFD detection method we developed provides a novel approach for the rapid, simple, precise, and specific onsite diagnosis of pigeon Newcastle disease.

Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.

Abstract Rituximab has been incorporated into the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL), and induces the death of tumor cells via complement-dependent cytotoxicity (CDC). Unfortunately, the resistance of DLBCL cells to Rituximab limits its clinical usefulness. It remains unclear whether the complement system is related to Rituximab resistance in DLBCL. A Rituximab-resistant DLBCL cell line (Farage/R) was generated under the stress of Rituximab. Constituent proteins of the complement system in wild-type Farage cells (Farage/S) and Farage/R cells were analyzed by qPCR, western blotting, and immunofluorescence. In vitro and in vivo knockdown and overexpression studies confirmed that the complement 1Q subcomponent A chain (C1qA) was a regulator of Rituximab resistance. Finally, the mechanism by which C1qA is regulated by m6A methylation was explored. The reader and writer were identified by pull-down studies and RIP-qPCR. Activity of the complement system in Farage/R cells was suppressed. C1qA expression was reduced in Farage/R cells due to post-transcriptional regulation. Furthermore, in vitro and in vivo results showed that C1qA knockdown in Farage/S cells decreased their sensitivity to Rituximab, and C1qA overexpression in Farage/R cells attenuated the Rituximab resistance of those cells. Moreover, METTL3 and YTHDF2 were proven to be the reader and writer for m6A methylation of C1qA, respectively. Knockdown of METTL3 or YTHDF2 in Farage/R cells up-regulated C1qA expression and reduced their resistance to Rituximab. In summary, the aberrant downregulation of C1qA was related to Rituximab resistance in DLBCL cells, and C1qA was found to be regulated by METTL3- and YTHDF2-mediated m6A methylation. Enhancing the response of the complement system via regulation of C1qA might be an effective strategy for inhibiting Rituximab resistance in DLBCL.

[This corrects the article DOI: 10.1371/journal.ppat.1006851.].

Background: The enhancement of DNA damage repair is one of the important mechanisms of platinum resistance. Protein cell division cycle 7 (CDC7) is a conserved serine/threonine kinase that plays important roles in the initiation of DNA replication and is associated with chemotherapy resistance in ovarian cancer. However, whether the CDC7 inhibitor XL413 has antitumor activity against ovarian cancer and its relationship with chemosensitivity remain poorly elucidated. Methods: We evaluated the antitumor effects of carboplatin combined with XL413 for ovarian cancer in vitro and in vivo. Cell viability inhibition, colony formation and apoptosis were assessed. The molecules related to DNA repair and damage were investigated. The antitumor effects of carboplatin combined with XL413 were also evaluated in SKOV-3 and OVCAR-3 xenografts in subcutaneous and intraperitoneal tumor models. Results: Sequential administration of XL413 after carboplatin (CBP) prevented cellular proliferation and promoted apoptosis in ovarian cancer (OC) cells. Compared with the CBP group, the expression level of RAD51 was significantly decreased and the expression level of γH2AX was significantly increased in the sequential combination treatment group. The equential combination treatment could significantly inhibit tumor growth in the subcutaneous and intraperitoneal tumor models, with the expression of RAD51 and Ki67 significantly decreased and the expression of γH2AX increased. Conclusions: Sequential administration of CDC7 inhibitor XL413 after carboplatin can enhance the chemotherapeutic effect of carboplatin on ovarian cancer cells. The mechanism may be that CDC7 inhibitor XL413 increases the accumulation of chemotherapy-induced DNA damage by inhibiting homologous recombination repair activity.

This paper concentrates on the general birth–death processes with two different types of catastrophes. The Laplace transform of transition probability function for birth–death processes with two-type catastrophes is successfully expressed with the Laplace transform of transition probability function of the birth–death processes without catastrophe. The first effective catastrophe occurrence time is considered. The Laplace transform of its probability density function, expectation and variance are obtained.

SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE−/− mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE−/− mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.

FeCoCu pre-alloy powder was added into tungsten carbide matrix to find out the influence law of FeCoCu content and sintering temperature on matrix performance, aiming to improve the adaptability between bit matrix wear resistance and formation abradability and to enhance the self-sharpening ability of the bits. The ratio of FeCoCu to WC powder was adjusted and the matrix were sintered at different sintering temperatures. The test results show that with the increase of FeCoCu content, the performances of the matrix decrease, namely relative density, hardness, bending strength and wear resistance. It is also found that the sintering temperature has a significant impact on the wear resistance of the matrix, the maximum change of which reaches 310%; but it has small impact on other performances such as relative density, hardness and bending strength. In conclusion, the coupling effect of FeCoCu pre-alloy and sintering temperature provides a wide adjusting range for the wear resistance of the bits, whose adaptability to formations could be improved through the two-way adjustment of the two parameters.

IntroductionThere are not enough nurses around the world, and there are even fewer male nurses. It has not been easy for men to become nurses because of stereotypes about the roles of men and women in the workplace, which lead to prejudice and discrimination. This study explored how the self-esteem of male nurses and male nursing students affects their professional identity in an environment where stereotypes and social prejudice exist. This study also examined the differences of relevant variables in different sociodemographic characteristics of the research subjects in a Chinese social context.MethodsBy purposive and snowball sampling, 464 male nurses and male nursing students were surveyed through questionnaires from November 2021 to January 2022. Data analysis was performed using SPSS 25.0 and PROCESS Macro 3.3.ResultsSelf-esteem could indirectly affect professional identity through perceived prejudice and psychological distress. Nonetheless, self-esteem still had a significant direct effect on professional identity. The total mediating effect accounted for 32.816% of the total effect, and the direct effect accounted for 67.184% of the total effect. Also of note was that 81.7% of participants reported experiencing psychological distress.DiscussionTo improve the professional identity of male nurses and male nursing students, nursing educators and administrators should do the following: protect and improve their self-esteem; take steps to reduce social prejudice against them; value their mental health and alleviate their psychological distress.

Bacteriophages are viruses that infect bacteria. Bacteria and bacteriophages have been fighting for survival. Over time, the evolution of both populations has been affected. Pathogenic Flavobacteriaceae species including Riemerella anatipestifer mainly infects ducklings, geese, and turkeys. However, it does not infect humans, rats, or other mammals, and is a suitable and safe research object in the laboratory. Our previous study showed that there is a 10K genomic island in R. anatipestiferIn this study, we found another integrated 50K genomic islands and focused on the relationship between R. anatipestifer genomic islands and the RAP44 phage genome. The phage RAP44 genome was integrated into R. anatipestifer chromosome, and an evolutionary relationship was evident between them in our comparative analysis. Furthermore, the integrated defective RAP44 phage sequence had the function of integration, excision, and cyclization automatically. Integrases are important integration elements. The integrative function of integrase was verified in R. anatipestifer. The integrase with the attP site can be integrated stably at the attB locus of the R. anatipestifer genome. A recombinant strain can stably inherit and express the exogenous gene. By studying the integration between host bacterium and phage, we have provided evidence for the evolution of the genomes in R. anatipestifer.

Abstract Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

Patients with epidermolysis bullosa (EB) could develop significant urological complications, such as hydroureteronephrosis, renal amyloidosis and IgA nephropathy (IgAN). Here, we presented a 12-year-old boy carrying pathogenic COL7A1 mutation with diagnosis of dystrophic epidermolysis bullosa (DEB). The patient had concomitant gross hematuria and proteinuria. Pathological examinations and immunostaining of renal biopsy showed glomeruli with mesangial hypercellularity and deposition of IgA, which were indicative of IgAN. Interestingly, serological evaluation showed antineutrophil cytoplasmic antibody (ANCA) directed against myeloperoxidase and proteinase 3. Treatment with glucocorticoid, immunosuppressants, angiotensin-converting enzyme inhibitor and antibiotics efficiently improved hemato-proteinuria, and ANCAs became negative as well. This case of DEB presented a unique collection of clinical manifestations and pathological alterations. IgAN and serum positive ANCA were possibly associated with sustained infection secondary to DEB, and can be managed by empirical treatment for primary IgAN.

ObjectiveTo investigate dentists’ psychological status and influencing factors in Shaanxi Province during the COVID-19 epidemic and assess their perceived wellness.MethodsThe study was conducted among dentists from Shaanxi Province in China. The basic information was collected through the network questionnaire star platform. Depression, Anxiety, and Stress Scales (DASS-42) and Perceived Wellness Survey (PWS) were used to assess subjects’ psychological status and perceived wellness. Univariate linear regression analysis and multivariate analysis were performed on the influencing factors of depression, anxiety, and stress, and t-test and analysis of variance were used to analyze the perceived wellness results.ResultsThe results demonstrated that 33.2% of the surveyed dentists were in a state of depression, 37.1% were anxious, and 34.4% reported stress among 256 subjects. Linear Regression analysis results showed that: “years of working,” “the impact of COVID-19 on their life, work, and sleep,” “worrying about occupational exposure/virus infection,” “lacking the awareness of prevention and control measures,” “overtime work during the epidemic,” “worrying about participating in the supporting work,” and “continuous exhaustion from work” were significant contributors to depression, anxiety, and stress status. In addition, the results of PWS found that each dimension of PWS was correlated with depression, anxiety, and stress state, which indicates the individual’s physical and mental health state was associated with multiple factors.ConclusionCOVID-19 has significantly impacted dentists’ mental health in Shaanxi Province. With these findings, we aim to educate and promote targeted interventions that can be utilized to improve dentists’ mental health by analyzing the influencing factors.

Pseudorabies virus (PRV) variants have caused substantial economic losses in the swine industry in China since 2011. To surveil the genetic variation in PRV field strains, here, two novel variant strains of PRV were isolated from Shanxi Province in central China and were designated SX1910 and SX1911. To identify the genetic characteristics of the two isolates, their complete genomes were sequenced, and phylogenetic analysis and sequence alignment revealed that field PRV variants have undergone genetic variations; notably, the protein-coding sequences UL5, UL36, US1 and IE180 exhibited extensive variation and contained one or more hypervariable regions. Furthermore, we also found that the glycoproteins gB and gD of the two isolates had some novel amino acid (aa) mutations. Importantly, most of these mutations were located on the surface of the protein molecule, according to protein structure model analysis. We constructed a mutant virus of SX1911 with deletion of the gE and gI genes via CRISPR/Cas9. When tested in mice, SX1911-ΔgE/gI-vaccinated mice were protected within a comparable range to Bartha-K61-vaccinated mice. Additionally, a higher dose of inactivated Bartha-K61 protected the mice from lethal SX1911 challenge, while a lower neutralization titer, higher viral load and more severe microscopic lesions were displayed in Bartha-K61-vaccinated mice. These findings highlight the need for continuous monitoring of PRV and novel vaccine development or vaccination program design for PRV control in China.

In this work, a new technique of self-consumption friction plug spot welding (SFPSW) was introduced to spot welding of Ti–6Al–4V alloy sheets using a semi-consumable welding tool, and defect-free joints were successfully produced. The semi-consumable welding tool consists of a nickel-based superalloy shoulder and a titanium alloy plug. The spot welding parameters were discussed, and the effect of welding parameters on the microstructure and mechanical properties of the joints was investigated. The cross-section of the welding zone was divided into five regions: base metal (BM), heat-affected zone (HAZ), thermo-mechanically affected zone (TMAZ), stir zone (SZ), and filled zone (FZ). The final joint interface has a basket-weave structure. The maximum tensile-shear load of the joint was up to 69.5 kN and the hardness value of the welding region was lower than that of base metal. The failure mode of the tensile-shear test was a typical quasi-cleavage fracture.

Abstract Background To observe the effects of chalazion and its treatments on meibomian gland function and morphology in the chalazion area. Methods This nonrandomized, prospective observational clinical study included 58 patients (67 eyelids) who were cured of chalazion, including 23 patients (23 eyelids) treated with a conservative method and 35 patients (44 eyelids) treated with surgery. Infrared meibomian gland photography combined with image analysis by ImageJ software was used to measure the chalazion area proportion. Slit-lamp microscopy was employed to evaluate meibomian gland function, and a confocal microscope was used to observe meibomian gland acinar morphology before treatment and 1 month after complete chalazion resolution. Results At 1 month after chalazion resolution, the original chalazion area showed meibomian gland loss according to infrared meibomian gland photography in both groups. In patients who received conservative treatment, the meibomian gland function parameters before treatment were 0.74 ± 0.75, 0.48 ± 0.67, and 1.22 ± 0.60, respectively. One month after chalazion resolution, the parameters were 0.35 ± 0.49, 0.17 ± 0.49, and 0.91 ± 0.60, respectively; there was significant difference (P 0.05). In patients who underwent surgery, the meibomian gland function parameters before surgery were 0.93 ± 0.87, 1.07 ± 0.70, and 1.59 ± 0.76, respectively, and at 1 month after chalazion resolution, they were 0.93 ± 0.82, 0.95 ± 0.75, and 1.52 ± 0.70, respectively; there was no significant difference (P > 0.05). The proportion of the chalazion area before surgery was 14.90 (12.04, 21.6), and the proportion of meibomian gland loss at 1 month after chalazion resolution was 14.84 (11.31, 21.81); there was no significant difference (P > 0.05). The acinar structure could not be observed clearly in the meibomian gland loss area in most patients. Conclusions Chalazion causes meibomian gland loss, and the range of meibomian gland loss is not related to the treatment method but to the range of chalazion itself. A hot compress as part of conservative treatment can improve meibomian gland function at the site of chalazion in the short term.

Copy number variation (CNV) is an important type of mutation in the human genome, and is significantly associated with cancer and other diseases. Accurate detection of CNVs in tumor genomes is crucial for biologists aiming to understand tumorigenesis. One of the key steps in this task is to establish a reasonable model to conduct meaningful assessment of each genome region. Although a great number of computational approaches have been developed in the past few years, none of them is versatile enough to detect CNVs in all scenarios associated with complex genomes. In this paper, we propose a new statistical approach, called CRSCNV, to detect CNVs in individual samples, based on next-generation sequencing data. The approach adopts a cross-model-based statistical strategy to test the significance of genome bins, i.e., the genome to be analyzed is divided into N parts. The bins in each part are tested by establishing a statistical model based on the remaining (N - 1) parts. The advantage of such a cross model is that it can improve the meaning of P-value assessment. We tested the performance of CRSCNV on a large number of simulation datasets and compared it to the state-of-the-art methods. The results demonstrated that CRSCNV achieved the best trade-off between recall and precision. We further validated CRSCNV, using several real sequencing samples, where it produced a number of previously reported CNVs and some additional CNVs with potential biological importance. Thus, CRSCNV is a reliable approach for CNV detection, even in scenarios of extremely low purity.

Comprehensive identification and cataloging of copy number variation (CNVs) are essential to providing a complete view of human genetic variation and to finding diseased genes. Due to the large-scale sequencing and cost control whole-genome sequencing (WGS) data, low-coverage data is favorably disposed towards CNV identification. However, such low-coverage data is sensitive to noise and sequencing biases, which results in low resolution of CNV detection in past experimental designs for WGS datasets. In this paper, we present a control-free Dirichlet process Gaussian mixture model (dpGMM) based approach, to analyze the read depth (RD) of low-coverage WGS datasets for CNV discovery. First, noise and biases of the RD signals are corrected through the preprocessing step of dpGMM. Then we assume that RD signals across genomic regions follow a Gaussian mixture model (GMM) in which each Gaussian distribution is followed by a copy number state. Without requiring the number of Gaussian distributions, dpGMM builds a Dirichlet process (DP) GMM for RD signals and further uses a DP prior to infer the number of Gaussian models. After that, we apply dpGMM to simulation datasets with different coverages and individual datasets, and compare ours to three widely used RD-based pipelines, CNVnator, GROM-RD, and BIC-seq2. Simulation results demonstrate that our approach, dpGMM, has a high F1 score in both low- and high- coverage sequences. Also, the number of overlaps between CNVs detected in real data by ours and the standard benchmark is twice as much as that detected by other tools such as CNVnator and GROM-RD.

Abstract (Z)-Cinnamate derivatives are prevalent in natural bioactive products and in organic synthesis. Herein, we report a practical approach toward the efficient synthesis of (Z)-cinnamate derivatives via visible-light-driven isomerization. When E-isomers of cinnamate derivatives were irradiated with blue light in the presence of 1 mol% Ir2(ppy)4Cl2 (ppy = 2-phenylpyridine), Z-isomers were readily obtained in good yields. This strategy allows the large-scale synthesis of (Z)-cinnamate derivatives with simple purification. This convenient, mild, and green synthetic methodology was subsequently applied to the synthesis of coumarins.

Abstract Background Viral respiratory infection (VRI) is a common contraindication to elective surgery. Asymptomatic shedding among pediatric surgery patients (PSPs) could potentially lead to progression of symptomatic diseases and cause outbreaks of respiratory diseases. The aim of this study is to investigate the incidence of infection among mild symptomatic PSP group and asymptomatic PSP group after surgical procedure. Methods We collected the induced sputum from enrolled 1629 children (under 18 years of age) with no respiratory symptom prior to pediatric surgery between March 2017 and February 2019. We tested 16 different respiratory virus infections in post-surgery mild symptomatic PSP group and asymptomatic PSP group using a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay panel. We analyzed symptom data and quantitative viral load to investigate the association between viruses, symptoms and viral quantity in qRT-PCR-positive PSPs. Results Out of 1629 children enrolled, a total of 204 respiratory viruses were present in 171 (10.50%) PSPs including 47 patients with mild symptoms and 124 with no symptoms after surgery. Commonly detected viruses were human rhino/enterovirus (HRV/EV, 42.19%), parainfluenza virus 3 (PIV3, 24.48%), coronavirus (CoV NL63, OC43, HKU1, 11.46%), and respiratory syncytial virus (RSV, 9.9%). PIV3 infection with a higher viral load was frequently found in PSPs presenting with mild symptoms, progressing to pneumonia with radiographic evidence after surgery. HRV/EV were the most commonly detected pathogens in both asymptomatic and mild symptomatic PSPs. CoV (OC43, HKU1) infections with a higher viral load were mostly observed in asymptomatic PSPs progressing to alveolar or interstitial infiltration. Conclusions Our study suggested that PIV3 is a new risk factor for VRI in PSPs. Employing a more comprehensive, sensitive and quantitative method should be considered for preoperative testing of respiratory viruses in order to guide optimal surgical timing.

Inorganic nanomaterials with enzyme-like activity have been attracting much attention due to their low cost, favorable stability, convenient storage, and simple preparation. Herein, Co3O4 nanoplates with a uniform nanostructure were prepared by the thermolysis of cobalt hydroxide at different temperatures, and the influence of the annealing temperature on the performance of the mimetic enzyme also was reported for the first time. The results demonstrated that Co3O4 nanoplates obtained at an annealing temperature of 200 °C possessed strong oxidase activity and efficiently catalyzed the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) without the addition of hydrogen peroxide to generate the blue color product ox-TMB. Once the annealing temperature was increased to 500 °C and 800 °C, the oxidase activity of Co3O4 decreased rapidly, and was even inactivated. This might be attributed to the relatively large specific surface area of Co3O4 annealed at 200 °C. Besides this, based on the TMB-Co3O4 nanoplate system, a colorimetric analysis method was developed to detect dopamine with a limit of 0.82 μmol/L in a linear range from 1.6 μmol/L to 20 μmol/L.

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.

In the design of planetary sampling devices, calculating the reaction force acting on the sampling devices is crucial. According to related research, the influence zone caused by sampling plays an important role in calculating the reaction force. A new method for estimating the range of the influence zone based on 3D DEM simulation is discussed in this paper. Taking lunar soil as an example, first, via validation of physical experiments, the DEM lunar soil simulant was proven to have mechanical properties similar to those of real lunar soil. Second, stress was selected as an indicator to identify the influence zone by computing the match percentage via a comparison between classical soil mechanics and DEM simulation. Using the proposed calculation method, it can be observed that the trend of change of influence zone at different sampling moments showed similar to the change of reaction force. Calculation of the influence zone can be used to analyze the reaction force of different gravity environments, sampling device structures, and motions.

Trichomicin, a novel small-molecule compound isolated from the fungus Trichoderma harzianum and identified as new structure compound, exhibited antitumor activities in various human cancer cell lines and reversed drug resistance activity in the multidrug-resistant cancer cell line KBV. The underlying cellular and molecular mechanism was illuminated. Trichomicin can significantly induce cancer cell apoptosis and reduced IL-6 expression and phosphorylation of STAT3 were found in response to Trichomicin treatment. The blockade of IL-6 mediated JAK-STAT3 signaling pathway by Trichomicin was confirmed using reporter gene system. As a promising antitumor-activity compound, Trichomicin is presented in this study.

The behavior of rock mass is governed by the properties of both the rock material and discontinuities in the rock mass. Surrounding environments including the existence of water also have a great influence on the behavior and mechanical properties of rocks. In this study, a novel-designed compression and seepage testing system, associated with an acoustic emission system, was designed and constructed. The changes in the specimens resulting from the uniaxial compression were monitored by an acoustic emission technique. The characteristics of the acoustic emission parameters at different stages including compaction and crack initiation, crack propagation, and catastrophic failure were analyzed. The existence of seepage had direct influences on the mechanical properties and failure patterns of the specimens. The specimens tested in pure compression conditions demonstrated strong burst proneness and ruptured into separate pieces, while for the specimens with seepage, no burst proneness was observed and the specimens tended to fail along a macroscopic shear failure plane. The highest average energy of the acoustic signal occurred at the stage of initial rupture of rock specimens, rather than at the stage of widespread rupture. The studies explored the possibilities of using the acoustic emission technique to investigate the problems associated with the seepage in geotechnical and rock engineering and provided meaningful results for further research in this field.

Abstract Background Numerous protocols for viral enrichment and genome amplification have been created. However, the direct identification of viral genomes from clinical specimens using next-generation sequencing (NGS) still has its challenges. As a selected viral nucleic acid extraction method may determine the sensitivity and reliability of NGS, it is still valuable to evaluate the extraction efficiency of different extraction kits using clinical specimens directly. Results In this study, we performed qRT-PCR and viral metagenomic analysis of the extraction efficiency of four commonly used Qiagen extraction kits: QIAamp Viral RNA Mini Kit (VRMK), QIAamp MinElute Virus Spin Kit (MVSK), RNeasy Mini Kit (RMK), and RNeasy Plus Micro Kit (RPMK), using a mixed respiratory clinical sample without any pre-treatment. This sample contained an adenovirus (ADV), influenza virus A (Flu A), human parainfluenza virus 3 (PIV3), human coronavirus OC43 (OC43), and human metapneumovirus (HMPV). The quantity and quality of the viral extracts were significantly different among these kits. The highest threshold cycle(Ct)values for ADV and OC43 were obtained by using the RPMK. The MVSK had the lowest Ct values for ADV and PIV3. The RMK revealed the lowest detectability for HMPV and PIV3. The most effective rate of NGS data at 67.47% was observed with the RPMK. The other three kits ranged between 12.1–26.79% effectiveness rates for the NGS data. Most importantly, compared to the other three kits the highest proportion of non-host reads was obtained by the RPMK. The MVSK performed best with the lowest Ct value of 20.5 in the extraction of ADV, while the RMK revealed the best extraction efficiency by NGS analysis. Conclusions The evaluation of viral nucleic acid extraction efficiency is different between NGS and qRT-PCR analysis. The RPMK was most applicable for the metagenomic analysis of viral RNA and enabled more sensitive identification of the RNA virus genome in respiratory clinical samples. In addition, viral RNA extraction kits were also applicable for metagenomic analysis of the DNA virus. Our results highlighted the importance of nucleic acid extraction kit selection, which has a major impact on the yield and number of viral reads by NGS analysis. Therefore, the choice of extraction method for a given viral pathogen needs to be carefully considered.

ABSTRACT Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation upon replication in humans. Here, we generate a series of reassortant or mutant H7N9 AIVs and test them in mice. We show that the low polymerase activity attributed to the viral PA protein is the intrinsic driving force behind the emergence of PB2 E627K during H7N9 AIV replication in mice. Four residues in the N-terminal region of PA are critical in mediating the PB2 E627K acquisition. Notably, due to the identity of viral PA protein, the polymerase activity and growth of H7N9 AIV are highly sensitive to changes in expression levels of human ANP32A protein. Furthermore, the impaired viral polymerase activity of H7N9 AIV caused by the depletion of ANP32A led to reduced virus replication in Anp32a−/− mice, abolishing the acquisition of the PB2 E627K mutation and instead driving the virus to acquire the alternative PB2 D701N mutation. Taken together, our findings show that the emergence of the PB2 E627K mutation of H7N9 AIV is driven by the intrinsic low polymerase activity conferred by the viral PA protein, which also involves the engagement of mammalian ANP32A. IMPORTANCE The emergence of the PB2 E627K substitution is critical in the mammalian adaptation and pathogenesis of AIV. H7N9 AIVs that emerged in 2013 possess a prominent ability in gaining the PB2 E627K mutation in humans. Here, we demonstrate that the acquisition of the H7N9 PB2 E627K mutation is driven by the low polymerase activity conferred by the viral PA protein in human cells, and four PA residues are collectively involved in this process. Notably, the H7N9 PA protein leads to significant dependence of viral polymerase function on human ANP32A protein, and Anp32a knockout abolishes PB2 E627K acquisition in mice. These findings reveal that viral PA and host ANP32A are crucial for the emergence of PB2 E627K during adaptation of H7N9 AIVs to humans.

Because there are less restrictions in space, a variety of different movement patterns and equipment structures may be used during the process of planetary surface sampling. Traditionally, the optimal analysis for surface sampling is focused on specific equipment structures and movements; in contrast, a new modular motion-structure design model for surface sampling, which is a more flexible model, is discussed in this paper. By establishing and combining two basic module groups, namely, the motion group and the structure group, this new design model can define and analyse multiple movement patterns and structures. For the motion group, calculating the sampling trajectory is the main purpose, in which there are two basic modules: tridimensional uniform rectilinear movements and tridimensional uniform circular movements. The two basic motion modules can be freely combined in a given coordinate system to simulate a random sampling trajectory. The structure group contains a series of curved and flat plates, which can be defined by a set of unified parameters (including section, extension, and cutting parameters). By assigning different values to these parameters, the curved or flat plates can represent different external shapes. The different structures of the various pieces of surface sampling equipment can be simulated by combining these different plates. In addition to defining these basic modules, analysing the coupling among different modules, which can be simplified to the relationship between velocity and surface, plays an important role in establishing this design model. Based on the modular design theory, this new model will not only reduce the difficulty of analysis but also improve accuracy for planetary surface sampling.

In this study, friction stir welding (FSW) of 2-mm-thick Ti–6Al–4V alloy plates was performed using a newly designed friction tool—and the effect of rotation speed and welding speed on microstructure and mechanical properties of the joints were investigated. A simulation model for FSW temperature field calculation was developed, and the effect of rotation speed and welding speed on the temperature field was investigated by experimental and numeric methods. The results show that the rotation speed has a dominant effect on peak temperature, while welding speed determines the dwell time of the weld exposed to high temperatures. In addition, the influence of process parameters on the microstructure of the joints was investigated using optical and scanning electron microscopy. The results revealed that there was a phase transformation in the stir zone during welding. The final microstructure of the stir zone was fully lamellar (α + β) structure, and the heat affection zone had a bimodal microstructure consisting of prior equiaxed α and lamellar (α + β) structure. Both rotation speed and welding speed affect the grain size of the weld. Lower peak temperature with decreasing spindle speed and/or shorter dwell time with increasing feed rate could produce finer grains in the stir zone of the joints, thereby could lead to higher microhardness value and the tensile strength of the joints.

Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen. The interaction between NP and PLSCR1 in mammalian cells was demonstrated by using co-immunoprecipitation and pull-down assays. We found that the stable overexpression of PLSCR1 suppressed the nuclear import of NP, hindered the virus life cycle, and significantly inhibited the replication of various influenza subtypes. In contrast, siRNA knockdown or CRISPR/Cas9 knockout of PLSCR1 increased virus propagation. Further analysis indicated that the inhibitory effect of PLSCR1 on the nuclear import of NP was not caused by affecting the phosphorylation status of NP or by stimulating the interferon (IFN) pathways. Instead, PLSCR1 was found to form a trimeric complex with NP and members of the importin α family, which inhibited the incorporation of importin β, a key mediator of the classical nuclear import pathway, into the complex, thus impairing the nuclear import of NP and suppressing virus replication. Our results demonstrate that PLSCR1 negatively regulates virus replication by interacting with NP in the cytoplasm and preventing its nuclear import.

Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions.

As potential biomarkers in periodontitis, microbiome, and cytokines have recently been extensively investigated, but combined analyses of the variations between the microbial structure and cytokine composition are rare. The present study aimed to investigate whether there are differences in the combined profile of microbiome and cytokines in individuals with or without periodontitis. The microbiome and cytokine composition in gingival crevicular fluid (GCF) from 16 patients and 15 controls from Jishi Shan (Gansu, China) were analyzed using 454 pyrosequencing and RayBio Quantibody Arrays. The results showed that a higher co-occurrence of genera in periodontitis group compared with the healthy group, as evaluated by Schoener's abundance-based co-occurrence index. C-reactive protein (CRP) was significantly (P < 0.05) higher in the GCF of the periodontitis group while interleukin (IL)-8 was significantly (P < 0.01) higher in the GCF of the healthy group. The Mantel test revealed a significant concordance between cytokines and microbiota, in the healthy group (Mantel statistic r = 0.36, P ≤ 0.05) but not in the periodontitis group (Mantel statistic r = 0.013, P = 0.434). The results were further confirmed by the Procrustes test. Matrix metalloproteinase (MMP)-9, osteoactivin, IL-8, and macrophage inflammatory protein (MIP)-1a were significantly associated with bacterial composition at the phylum, class, order, family, and genus levels. CRP was also associated with bacterial composition at the species level. In conclusion, alterations in the polymicrobial community structure leads to disruption in the healthy correlation between cytokines and microbiomes. This dysbiosis between the microbiota and the immune response could be one of the major etiological mechanisms underlying periodontitis.

Non-wood forest products (NWFPs) derived from understory plants are attracting attention about sustainable forestry development. Geographical distribution and climate correlates of bioactive compounds are important to the regional management for the natural reserves of medical plants in forests. In this study, we collected Eleutherococcus senticosus individuals from 27 plots to map the special distribution of concentrations of eleutheroside B, eleutheroside E, and isofraxidin in forests of Northeast China. Compound concentrations in both aerial and underground organs were further detected for relationships with the average of 20-year records of temperature, precipitation, and relative humidity (RH). We found higher shoot eleutheroside B concentration in populations in northern and low-temperature regions (R = −0.4394; P = 0.0218) and in eastern and high-RH montane forests (R = 0.5003; P = 0.0079). The maximum-likelihood regression indicated that both RH (Pr > Chi-square, 0.0201) and longitude (Pr > Chi-square, 0.0026) had positive contributions to eleutheroside B concentration in roots, but precipitation had strongly negative contributions to the concentrations of eleutheroside E (Pr > Chi-square, 0.0309) and isofraxidin (Pr > Chi-square, 0.0014) in roots. Both geography and climate factors had effects on the special distribution of medical compounds in E. senticosus plants in natural populations in Northeast China. The management of NWFP plants at the regional scale should consider effects from climatic geography.

Cable-bolt failures due to stress corrosion cracking (SCC) could significantly compromise the sustainability and long-term stability of underground constructions. To fully understand the SCC of cable bolts, a two-step methodology was implemented: (i) long-term cable-bolt coupon tests using mineralogical materials collected from underground mines; and (ii) accelerated full-scale cable-bolt tests using an acidified solution. In the long-term tests, a novel three-point bending coupon was designed. The effects of mineralogical materials on SCC were evaluated under the simulated underground bolting conditions through the application of “corrosion cells”. For accelerated tests, SCC resistance of different type of cable bolts was examined using the new designed tensile-loading apparatus under the periodically increasing strain-rate loading mechanism. It was identified that mineralogical materials and applied stress intensity accelerated the corrosion process of the cable bolts. The number of wires and wire surface conditions in different types of cable bolt directly affected SCC susceptibility. The cable bolts with a greater number of wires provided higher resistance to SCC. The developed experimental methodologies can be applied to study SCC in other reinforcement materials and the results can be used to design optimal support systems in different environmental and geotechnical conditions.

In this article, we are concerned with the E-Bayesian (the expectation of Bayesian estimate) method, the maximum likelihood and the Bayesian estimation methods of the shape parameter, and the reliability function of one-parameter Burr-X distribution. A hybrid generalized Type-II censored sample from one-parameter Burr-X distribution is considered. The Bayesian and E-Bayesian approaches are studied under squared error and LINEX loss functions by using the Markov chain Monte Carlo method. Confidence intervals for maximum likelihood estimates, as well as credible intervals for the E-Bayesian and Bayesian estimates, are constructed. Furthermore, an example of real-life data is presented for the sake of the illustration. Finally, the performance of the E-Bayesian estimation method is studied then compared with the performance of the Bayesian and maximum likelihood methods.

Objective: To explore the feasibility of a modified 3D porous small intestinal submucosa (SIS) scaffold seeded with urothelial cells (UC) for surgical reconstruction in a rabbit model. Material and methods: Eighteen New England white male rabbits were divided into three groups and a 0.8 × 1.5 cm2 section of the anterior urethral mucosa was removed from each animal. Ventral onlay urethroplasty was performed with a 1.0 × 1.7 cm2 SIS scaffold that was either cell-seeded and treated with 5% peracetic acid (PAA) (n = 6), or cell-seeded and untreated (n = 6), or unseeded and treated with 5% PAA (n = 6). Animals were sacrificed at 6 months post-repair and retrograde urethrography and histological analyses performed. Results: In animals implanted with cell-seeded and PAA treated SIS scaffolds, urethrography showed wide-caliber urethra without any signs of stricture or fistulae, and histological analyses confirmed a complete urethral structure. In contrast, ulceration and fistula occurred in the reconstructed urethra of animals implanted with cell-seeded but untreated SIS scaffolds, and evident stricture was present in the unseeded, PAA treated group. Histological analyses demonstrated less urothelial coverage and smooth muscle in the cell-seeded and untreated SIS scaffold group, and serious fibrosis formation occurred in the unseeded, treated group. Conclusions: A modified 3D porous SIS scaffold seeded with UC and treated with PAA produces better urethroplasty results than cell-seeded untreated SIS scaffolds, or unseeded PAA treated SIS scaffolds.

Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential "differentiating infected from vaccinated animals" (DIVA) vaccine candidates for the surveillance and eradication of PPR.

The nonautonomous stochastic Gilpin-Ayala competition model driven by Lévy noise is considered. First, it is shown that this model has a global positive solution. Then, we discuss the asymptotic behavior of the solution including moment and pathwise estimation. Finally, sufficient conditions for extinction, nonpersistence in the mean, and weak persistence of the solution are established.

MgO/MCM-41 materials with weak basic sites were synthesized by dispersing MgO onto mesoporous Si-MCM-41. Such MgO-modified MCM-41 materials were characterized by Fourier-transform infrared spectroscopy (FT-IR), temperature programmed desorption (TPD), X-ray diffraction (XRD) and N 2 adsorption/desorption measurements. The results indicated that the surface area, pore size and pore volume of the materials decreased with the introduction of MgO. Their CO 2 uptakes could be significantly improved when the MgO loading was increased from 0 wt% to 20 wt%. CO 2 -TPD and in situ FT-IR measurements showed that the materials possessed weak basic sites which could react with CO 2 to form bicarbonate species and thereby improve the CO 2 uptake. As a result, the adsorbed CO 2 could be desorbed completely from the sample at 200 °C. In addition, the MgO/MCM-41 materials had a high thermal stability and showed promising performances in practical applications.

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

The main objective of this study was observe the distribution and expression of tau in the distal colonic muscle layers using opioid-induced constipation (OIC) rat model and to explore the mechanistic correlation between the tau phosphorylation and occurrence of OIC. The rat model of OIC was generated by intraperitoneal (i.p) injection of loperamide hydrochloride (Lop; 5mg/kg), and was evaluated by examining the fecal properties, intestinal propulsion mobility, immunohistochemistry (IHC), western blot (WB) and ELISA for detecting levels of Tau, P-Ser396-tau, P-Ser404-tau, protein kinase C (PKC), p38 MAPK (p38), p-p38 MAPK (p-p38) and µ-opioid receptors (MORs) in the colonic samples. The gene sequencing approach was used to detect alternatively spliced tau isoforms in the distal colonic muscle layer. Sequencing analysis revealed that 3 isoforms of tau, namely 2N4R, 1N4R and 0N4R were expressed in the distal colonic myocardium tissue. OIC rats had small, dry and hard feces, and intestinal propulsion velocity was significantly slower, especially in the distal colon. P-Ser396-Tau, P-Ser404-Tau, PKC, p-p38, p38, and Tau positive cells were distributed in the intestinal muscle plexus of the distal colon, and all of them were colocalized with MORs; though the expressions levels of tau and p38 remained unchanged, others indexes above significantly increased in the distal colonic muscle layer of OIC rats. However, after the administration of p38 blocker SB203580, OIC rats had salami-like feces, with an increase in colonic propulsion velocities; although the expressions levels of Tau and p38 didn't change significantly in distal colonic muscle layers, the expressions levels of P-Ser396-Tau, P-Ser404-Tau, and p-p38 significantly reduced. To conclude there is a unique distribution pattern of tau within the distal colonic musculature of OIC rats. The abnormal activation of MORs contributes to the hyperphosphorylation of tau protein, which in turn induces the development of OIC. [ABSTRACT FROM AUTHOR]