Search

The accurate determination of sugar content in tangerines plays a pivotal role in assessing their quality, nutritional value, and marketability. Traditional methods for sugar quantification often involve time-consuming and resource-intensive processes. In this paper, we introduce a novel approach for sugar determination in tangerines utilizing fluorescence spectroscopy in conjunction with an improved Partial Least Squares (iPLS) algorithm. A robust testing model was developed, incorporating a diverse dataset of tangerine samples with known sugar concentrations. Fluorescence spectra were acquired for 80 samples, of which 37 were used to build the iPLS model and were considered as the training dataset. The remaining 43 samples served as the validation dataset and were used to show the model’s efficacy. The training dataset was evaluated using cross-validation, and F -values were computed to determine how many main components should be utilized to build the model. The result approved validation dataset’s R -square and root-mean-square error were 0.9777 and 0.002992, respectively. These findings open the door to broader applications in the citrus industry and beyond, with the potential for automating the analysis process and improving overall quality control.

Logistics is an essential service for manufacturing because it supports the coordination and integration of global production activities, ultimately reducing costs and improving efficiency. However, it is not clear that the complex structural relationship between logistics and manufacturing under the Global Value chains (GVCs). Consequently, employing the input-output model, we develop the logistics input complexity (LIC) to capture the complex structural characteristics of logistics services embodied in manufacturing sectors and investigate its role in manufacturing comparative advantage. We find that the logistics input complexity can boost manufacturing competitiveness. Furthermore, we also confirm that the domestic and foreign groups of LIC have at least a partially complementary effect on the export competitiveness of manufacturing. Finally, we identify heterogeneity in the domestic and foreign groups’ five subdivision logistics modes of LIC. It suggests that logistics service providers must precisely match the related manufacturing production chains to cultivate a comparative advantage in manufacturing.

The study aimed to screen for the possible presence of lactic acid bacteria (LAB) in cat milk in order to evaluate their probiotic properties. The isolates were characterized by biochemical identification, morphological tests and 16S rDNA sequencing. Afterward, gastrointestinal passage, in vitro safety and probiotic properties were evaluated. The results showed that the isolates had 10 strains of Pediococcus acidilactici permitted in the feed additive catalog. The high survival rate in the acid and bile salt resistance test reflected the good strain tolerance of the isolates to the simulated gastrointestinal conditions of the host in vitro. The mean inhibitory diameters of the 10 strains against chloramphenicol and tetracycline were 23.6 mm and 17.4 mm, respectively; none of the hemolytic tests showed α/β hemolytic ring. The bacteriostatic test showed that P. acidilactici YH-9, YH-14 and YH-15 had inhibitory effects on four common pathogenic bacteria, including Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Streptococcus. The adhesion test showed that P. acidilactici YH-15 had good adhesion to HT-29 cells. Based on these results, we concluded that P. acidilactici YH-15 extracted from cat milk has potential application as a clinical probiotic therapy and health care product.

Excessive reactive oxygen species stress due to salinity poses a significant threat to the growth of Glycyrrhiza uralensis Fisch. To adapt to salt stress, G. uralensis engages in alternative splicing (AS) to generate a variety of proteins that help it withstand the effects of salt stress. While several studies have investigated the impact of alternative splicing on plants stress responses, the mechanisms by which AS interacts with transcriptional regulation to modulate the salt stress response in G. uralensis remain poorly understood. In this study, we utilized high-throughput RNA sequencing data to perform a comprehensive analysis of AS events at various time points in G. uralensis under salt stress, with exon skipping (SE) being the predominant AS type. KEGG enrichment analysis was performed on the different splicing genes (DSG), and pathways associated with AS were significantly enriched, including RNA transport, mRNA surveillance, and spliceosome. This indicated splicing regulation of genes, resulting in AS events under salt stress conditions. Moreover, plant response to salt stress pathways were also enriched, such as mitogen-activated protein kinase signaling pathway – plant, flavonoid biosynthesis, and oxidative phosphorylation. We focused on four differentially significant genes in the MAPK pathway by AS and qRT-PCR analysis. The alternative splicing type of MPK4 and SnRK2 was skipped exon (SE). ETR2 and RbohD were retained intron (RI) and alternative 5’splice site (A5SS), respectively. The expression levels of isoform1 of these four genes displayed different but significant increases in different tissue sites and salt stress treatment times. These findings suggest that MPK4, SnRK2, ETR2, and RbohD in G. uralensis activate the expression of isoform1, leading to the production of more isoform1 protein and thereby enhancing resistance to salt stress. These findings suggest that salt-responsive AS directly and indirectly governs G. uralensis salt response. Further investigations into AS function and mechanism during abiotic stresses may offer novel references for bolstering plant stress tolerance.

Abstract Background The prevalence of diabetes and obesity has been continuously rising worldwide over the last three decades, particularly in China. The prevalence varies widely among different ethnicities. In this study, we investigated the prevalence of diabetes and obesity, as well as the associated factors for diabetes in Kazakh adults in Xinjiang to improve diabetes screening. Methods We collected data from the Xinjiang physical examination in 2018, including a total sample of 118,505 Kazakh adults in Altay District. Data on demographic characteristics, medical history, physical examination, fasting plasma glucose (FPG) and serum lipid profiles were collected. The chi-square test was used to examine the differences between multiple variables. Multivariate logistic regression was performed to identify the factors associated with diabetes. Results The mean age was 43. 66 years (SD 14.14). 49.3% of the population were women and 75.5% were rural residents. The mean FPG was 5.33 mmol/L (SD 1.22). The prevalence of diabetes was 6.3% and 4.1% received a new diagnosis by FPG. 26.6% were diagnosed with impaired fasting glucose (IFG). The mean body mass index (BMI) was 26.29 kg/m2 (SD 14.14) and the mean waist circumference was 87.69 cm (SD 12.74). 33.2% of the population were overweight, and 33.0% were obese. The prevalence of central obesity was 51.4%. Diabetes was mostly positively associated with hypertension (OR = 3.821, P

Diffuse Large B-cell lymphoma (DLBCL) is a highly aggressive disease with heterogeneous outcomes and marked variability in the response to chemotherapy. DLBCL comprises two major subtypes: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Our study highlights the extensive antitumour activity of artesunate (ART) against both major DLBCL subtypes. Transcriptome analysis suggests the potential involvement of ferroptosis in artesunate-induced cell death. Because of low glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with the accumulation of free iron (Fe2+), artesunate induces the excessive production of reactive oxygen species (ROS), ultimately leading to ferroptosis, a form of cell death driven by phospholipid peroxidation. A putative target of artesunate, metallothionein 1G (MT1G), was selected for further analysis. Subsequent studies revealed that inhibiting MT1G expression in vitro significantly impedes the ferroptosis-promoting activity of artesunate by reducing lipid peroxidation and iron accumulation. We also showed that the combination of artesunate and doxorubicin had a marked additive inhibitory effect on GCB and ABC DLBCL cells. In conclusion, artesunate induces ferroptotic death in GCB and ABC DLBCL cells by attenuating the GPX4/GSH antioxidant defence system and increasing intracellular iron levels, indicating its therapeutic potential for relapsed or refractory DLBCL.

Abstract Objective To understand the status and influencing factors of Kyrgyz chronic disease prevention literacy, and to explore the impact of chronic disease prevention literacy on behavior and living habits. Method Using stratified sampling method, Kyrgyz residents aged ≥ 18 years in Artush City, Aheqi County and Ucha County were surveyed by questionnaire. Results A total of 10,468 subjects were investigated, and the literacy rate of chronic disease prevention in Kyrgyz was 11.2%. The results of Logistic regression analysis showed that the literacy rate of chronic disease prevention was low among people with low education level, herdsmen, low income, urban and chronic disease (P

The defects of the cast-in-place bored piles heavily influence their integrities and bearing capacities. The bearing capacity and reliability index of the cast-in-place bored piles with different defects were studied using the finite element method. The accuracy of the numerical model is verified by the field test results of an in situ cast-in-place bored pile. Parametric studies are conducted to investigate the toe debris, mud cake, and necking and bulging defects on the ultimate bearing capacities of the cast-in-place bored piles. The results indicate that maximum reduction in the ultimate bearing capacities of the cast-in-place bored pile was observed, with the ultimate bearing capacity of the toe debris defect decreased by 17%, that of the mud cake defect decreased by 19%, that of the necking defect by 6.1%, and that of the pile bulging defect increased by 40.9%. The minimum reliability index can be 0.81 when the diameter of the pile necking defect is 0.2 m. The maximum reliability index can be 3.63 when the diameter of the pile necking defect is 2.0 m.

ObjectiveThe Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility.MethodsBetween 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs).ResultsIn a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(PConclusionThe AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.

BackgroundProkinetic agents are currently considered the first-line therapy to improve gastric emptying when feeding intolerance occurred in critically ill adults. In this study, we developed a technique to assess the feasibility of predicting prokinetic agent efficacy in critically ill patients.MethodsThe first images of each patient were obtained after EFI had occurred but before the first dose of prokinetic agents was administered and additional images were obtained every morning until the seventh day. The gastric antrum echodensity was recorded based on grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean) and daily energy and protein intake was collected as the judgment for effective and ineffective group. A receiver operating characteristic curve was analyzed to distinguish the thresholds between the two groups and thus determine the ability of the gastric antrum echodensity to predict the efficacy of prokinetic agents.ResultsIn total, 83 patients were analyzed. Patients in the ineffective group had a higher ED50 (58.13 ± 14.48 vs. 49.88 ± 13.78, p

Abstract Background Inorganic nanocomposites especially Au nanostructures have exhibited outstanding physicochemical properties in biomedical fields. For further clinical applications on theranostics, especially drug delivery, numerous explorations of green and facile synthesis methods combining with pharmacoactive natural components have been investigated to construct safe and multifunctional bioactive Au nanoparticles (NPs). Ginsenoside Rh2 is protopanaxadiol type compound isolated from plants of genus Panax, with excellent anticancer effect and antioxidant activity. In this research, we prepared the novel Au nanoparticles using ginsenoside Rh2 as both reducing and stabilizing agents. Results The synthesized Au@ginsenoside Rh2 NPs were proved to exhibit desirable inhibitory effect on different cancer cell lines, which benefited from the inherent anticancer effect of the ginsenoside Rh2. Investigations in vitro indicated that Au@ginsenoside Rh2 NPs inhibited cell proliferation, cell migration and invasion, induced cell cycle arrest, enhanced the reactive oxygen species (ROS) generation, and regulated the protein expressions of caspase-3, 8, 9 to trigger cell apoptosis as well. Conclusions Because of the absence of toxic chemical surfactants, the eco-friendly synthesis method of Au NPs modified by natural phytochemicals avoided tedious separation and modification processes. On the other hand, Au@ginsenoside Rh2 NPs also improved water solubility and bioavailability of the hydrophobic drug ginsenoside Rh2. It broadened minds for preparation and application of traditional Chinese medicines (TCMs) modified metal nanoparticles and deserved further study.

As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos’ stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.

ABSTRACT Hepatectomy is a common clinical procedure for the treatment of many liver diseases, and the successful recovery of a patient’s liver metabolism and function after surgery is crucial for a good prognosis. The objective of this study was to elucidate the metabolic response to hepatectomy using high-throughput sequencing analysis of 16S rRNA gene, metabolomics, and proteomics data. Fecal and serum samples from beagle dogs were collected on day 0 (LH0), day 7 (LH7), and day 28 (LH28) after laparoscopic partial hepatectomy. Liver tissue samples were taken on LH0 and LH7. Dysbiosis in the fecal microbiota was explored, and host-microbiome interactions based on global metabolic and protein profiles and inflammatory processes were determined. Results showed that the relative abundance of Allobaculum and Turicibacter was decreased and that of Escherichia-Shigella was increased after hepatectomy (P < 0.05); the phenylalanine, tyrosine, and tryptophan biosynthetic pathway, along with the phenylalanine and aminoacyl-tRNA biosynthetic pathway, was significantly associated with liver injury. The serum metabolites l-phenylalanine and l-arginine were useful as biomarkers, and the fecal metabolite l-threonine was a signature target monitor for liver recovery. The proteomics profile revealed 412 significantly different proteins and further highlighted two key signaling pathways (mitogen-activated protein kinase [MAPK] and peroxisome proliferator-activated receptor [PPAR]) involved in the response to liver injury. We systematically explored the metabolic mechanism of liver injury and recovery, providing new insights into effective ways to promote recovery after hepatectomy and improve liver function and long-term survival. These fundamental studies on hepatectomy will provide the basis for future advances in treatment and recovery from common liver diseases. IMPORTANCE As the largest parenchymal organ, the liver is a target for bacterial and viral infections, nonalcoholic fatty liver disease (NAFLD), cirrhosis, cancer, and many other diseases, constituting a serious worldwide problem. The treatment for many of these diseases involves hepatectomy. Here, we show that aberrant inflammatory processes after hepatectomy of the liver as reflected in the association between liver metabolism and gut microbiota create a grave risk. This study investigated the mechanisms of gut microbiota and host metabolism involved in liver injury and recovery after hepatectomy, using proteomics to reveal the mechanisms of postoperative liver injury and a comprehensive multi-omics approach to identify changes in metabolism after hepatectomy.

IntroductionGut motility dysfunction, the most common complication of post-septic organ dysfunction, depends on immune and neuronal cells. This study aimed to investigate the mechanisms that activate these cells and the contribution of macrophages to the recovery of intestinal motility dysfunction after sepsis.Materials and methodsPostoperative gut motility dysfunction was induced by establishing Klebsiella pneumonia sepsis in mice with selective deletion of neutrophils and macrophages in the gut. The distribution of orally administered fluorescein isothiocyanate-dextran and carmine excretion time was used to determine the severity of small bowel disease. The effect of macrophages on intestinal motility was evaluated after prostaglandin E2 therapy.ResultsWe found that muscular neutrophil infiltration leading to neuronal loss in the intestine muscle triggered intestinal motility dysfunction after pneumonia sepsis; however, reduced neutrophil infiltration did not improve intestinal motility dysfunction. Moreover, macrophage depletion aggravated gut motility dysfunction. The addition of macrophages directly to a smooth muscle was responsible for the recovery of intestinal motility.ConclusionOur results suggest that a direct interaction between macrophages and smooth muscle is neurologically independent of the restoration of intestinal dysmotility.

Objective. Many patients with type 2 diabetes have an abnormal body mass index (BMI) and hypertension together, but few studies on the interaction of the two on the risk of T2DM are reported. We aim to explore the effect of the interaction between abnormal BMI and hypertension on the risk of type 2 diabetes mellitus (T2DM) in Uyghur residents. Methods and Results. Based on the physical examination data of 27,4819 Uygur residents in Moyu County, a logistic regression model was used to analyze the correlation between BMI abnormality, hypertension, and T2DM disease, and then, the effect of their interaction on the risk of T2DM was evaluated by an additive model and a multiplicative model. The results showed that the detectable rate of T2DM was 5.58%, the proportion of abnormal BMI was 59.49%, and the proportion of hypertension was 25.14%. The risk of T2DM in people with an abnormal BMI and hypertension was higher than that in people with a normal weight and without hypertension, and the difference was statistically significant P

Background: The unprecedented COVID-19 pandemic has been spreading for a long time. However, it is unclear whether the pandemic influenced admission in a surgical pediatric intensive care unit (PICU) that never received COVID-19 patients during the early outbreak in China. Methods: A retrospective study was conducted in a surgical PICU in a tertiary hospital in Chengdu, China. We sought to describe the trend in admission numbers from January 2018 to April 2021. We explored the impact of the COVID-19 outbreak on PICU admission characteristics by including all patients younger than 18 years admitted to the PICU between January 23 and April 8 in 2020 and those admitted in the same time periods in prepandemic years (2018 and 2019) and in 2021. Results: The percentage of patients admitted to the PICU from the Chengdu region increased from 34.2 percent in 2019 to 40.4 percent in 2020, whereas that from other provinces decreased from 11.7 percent in 2019 to 5.8 percent in 2020 (P = 0.012). The median length of stay (LOS) in the PICU was significantly longer in the 2020 cohort (4.0 days) than in the 2019 cohort (2.0 days) (P < 0.001); the median hospital LOS was also significantly longer in the former (12.0 days) than in the latter (8.0 days) (P < 0.001). Hospital outcomes (P = 0.005) and primary diagnosis distributions (P = 0.025) between the 2020 and 2019 cohorts were both statistically significant. Conclusions: In a surgical PICU that never received COVID-19 patients, the onset of the 2020 major outbreak was accompanied by changes in the composition of the regional sources of patients, longer PICU and hospital stays, increased proportions of unauthorized discharges, and changes in the distribution of primary diseases for admission. These findings have yet to be strengthened by additional studies involving similar healthcare backgrounds.

To mitigate potential safety hazards during expressway operation, safety evaluation plays a crucial role. This study develops a fuzzy comprehensive evaluation model to assess the safety of expressway operations. First, an expressway operation safety risk assessment index system consisting of four criteria-layer indicators and 10 sub-criteria layer indicators is established. Then, the comprehensive weight of each evaluation index is calculated based on the combined AHP and entropy methods. Finally, the expressway safety level is obtained by converting qualitative indicators into fuzzy sets and defining corresponding membership functions to describe their degree of membership. The evaluation model is applied to the Jinliwen Expressway in a mountainous area in Zhejiang Province, China. The results show that the method could quantitatively and comprehensively evaluate the safety status of expressways and identify the weak links of operational safety management, which can effectively improve the safety level of expressway operations. The research findings will assist decision-makers in gaining a better understanding of the safety issues of expressways and, thus, using corresponding measures to enhance the safety level of the expressway.

Abstract Background Osteomyelitis variolosa is a self-limiting disease triggered by variola virus that cannot be prevented or repaired. Smallpox has been eradicated for 40 years, and complications that remain after smallpox has been cured have become a remarkable diagnostic challenge for contemporary physicians. In this systematic review, we searched PubMed (MEDLINE), Web of Science, and Google Scholar for cases on complications, diagnosis, and treatment for osteomyelitis variolosa between January 1980 and February 2021. Results Ten papers and eleven finished cases, all patients from India, were included for comparison with the present case. In total, 100% of patients presented with bilateral elbow deformities, the ankle was the second most common site of lesion in 50%, and knee lesions accounted for 25% in this study. Flexion contracture, joint instability, secondary arthritis, and fracture are common complications of osteomyelitis variolosa, and most patients receive conservative treatment, while internal fixation has good results for combined fractures. Conclusions Although osteomyelitis variolosa is not a direct threat to the safety of patients, severe skeletal deformities can have a significant impact on quality of life. With advances in surgical techniques, clinicians are offering an increasing number of treatment options for patients with osteomyelitis variolosa. However, most importantly, smallpox has basically been removed from the historical arena, and for areas where smallpox was once endemic, physicians need to deepen the understanding of this disease again.

BackgroundBovine metabolism undergoes significant changes during subclinical mastitis, but the relevant molecular mechanisms have not been elucidated. In this study we investigated the changes in milk microbiota and metabolites after intramammary infusion of matrine-chitosan hydrogels (MCHs) in cows with subclinical mastitis.MethodsInfusions were continued for 7 days, and milk samples were collected on days 1 and 7 for microbiome analysis by 16S rRNA gene sequencing and metabolite profiling by liquid chromatography-mass spectrometry.ResultsMCHs significantly decreased the somatic cell count on day 7 compared to day 1, and the Simpson index indicated that microbial diversity was significantly lower on day 7. The relative abundance of Aerococcus, Corynebacterium_1, Staphylococcus and Firmicutes was significantly decreased on day 7, while Proteobacteria increased. In the milk samples, we identified 74 differentially expressed metabolites. The MCHs infusion group had the most significantly upregulated metabolites including sphingolipids, glycerophospholipids, flavonoids and fatty acyls. The mammary gland metabolic pathways identified after MCHs treatment were consistent with the known antimicrobial and anti-inflammatory properties of matrine that are associated with glycerophospholipid metabolism and the sphingolipid metabolic signaling pathways.ConclusionThese insights into the immunoregulatory mechanisms and the corresponding biological responses to matrine demonstrate its potential activity in mitigating the harmful effects of bovine mastitis.

This study considers a multi-item production lot-size problem incorporating postponement, an external source for common parts, and an adjustable-rate for end products. Dealing with product variety, timely requirements, and limited in-house capacity has led production managers to seek manufacturing schemes and utilization-reduction strategies that can help them meet customer needs, smoothen fabrication schedules, and lower overall manufacturing expenses. We propose a two-stage manufacturing scheme. The first stage produces common parts for multiproduct incorporating a partial supply from an outside contractor to reduce utilization/uptime. Stage two fabricates all end products using an adjustable-rate to reduce the uptime further. We build a model to characterize the problem’s features and use optimization methods to derive the optimal rotation cycle time in order to help managers make cost-effective lot-size decisions and allow manufacturers to gain competitive advantages. A numerical illustration validates the model’s capability and applicability. This study makes two important contributions: (1) It offers a decision-support model for studying such a particular batch-size problem and deciding the optimal rotation cycle time, and (2) it identifies the individual/collective influence of dual uptime-reduction strategies on the operating policy and various performance indexes to help facilitate managerial decision-making.

Abstract Chimeric antigen receptor-based T-cell immunotherapy is a promising strategy for treatment of hematological malignant tumors; however, its efficacy towards solid cancer remains challenging. We therefore focused on developing nanobody-based CAR-T cells that treat the solid tumor. CD105 expression is upregulated on neoangiogenic endothelial and cancer cells. CD105 has been developed as a drug target. Here we show the generation of a CD105-specific nanobody, an anti-human CD105 CAR-T cells, by inserting the sequences for anti-CD105 nanobody-linked standard cassette genes into AAVS1 site using CRISPR/Cas9 technology. Co-culture with CD105+ target cells led to the activation of anti-CD105 CAR-T cells that displayed the typically activated cytotoxic T-cell characters, ability to proliferate, the production of pro-inflammatory cytokines, and the specific killing efficacy against CD105+ target cells in vitro. The in vivo treatment with anti-CD105 CAR-T cells significantly inhibited the growth of implanted CD105+ tumors, reduced tumor weight, and prolonged the survival time of tumor-bearing NOD/SCID mice. Nanobody-based CAR-T cells can therefore function as an antitumor agent in human tumor xenograft models. Our findings determined that the strategy of nanobody-based CAR-T cells engineered by CRISPR/Cas9 system has a certain potential to treat solid tumor through targeting CD105 antigen.

This study investigates the effect of stochastic breakdowns, overtime, and rework on the inventory replenishment decision. The overtime capacity and inevitable situations during the manufacturing process, such as the production of imperfect items and random breakdowns, are often considered in advance by production manager to smoothen fabrication schedules, maintain the desired quality, and reduce the impact from undesirable interruptions. This study builds a model to characterize these real features of a manufacturing process and derive the total relevant expenses of the system. Although a closed-form solution is unobtainable, a recursive algorithm is proposed to help find the optimal runtime for the batch fabrication plan. A numerical illustration shows how the proposed procedure and algorithm function. It also demonstrates the ability of the proposed model to reveal diverse crucial information regarding the individual and combined influences of deviations in overtime factors, the mean-time-to-failure, and rework- related variables, on the optimal replenishment runtime, total operating expenses, and different cost contributors. The research results will facilitate better decision-making aimed at increasing the competitive advantages of a manufacturing firm.

Conditionally automated driving is expected to become available to the public in near future. However, the driver is expected to take over control from the system when a sudden system failure occurs or when the driving automation system is approaching its operational design domain (ODD) exit. The time budget for drivers to take over control is different: (1) in the sudden system failure situation, the system needs to be deactivated immediately with issuing a request to intervene (RTI); (2) in the ODD exit situation, the system could keep active for a while after the issue of RTI. In this paper, two hypotheses were put forward based on driver’s expected utility analysis: (1) the drivers respond faster to the RTI in the system failure situation; (2) the drivers perform smoother driving behaviour after takeover in the ODD exit situation. We recruited 32 participants to conduct a driving simulator experiment, in which the driver takeover performance in system failure situation was compared with that in the ODD exit condition. Results revealed that drivers responded significantly faster in the system failure situation. There was no significant difference of longitudinal takeover performance between the two types of limitations. However, the drivers generally performed smoother lateral takeover performance in the ODD exit situation, which supported our hypothesis.

Alzheimer’s disease (AD) is a neurodegenerative disease with unknown pathogenesis and complex pathological manifestations. At present, a large number of studies on targeted drugs for the typical pathological phenomenon of AD (Aβ) have ended in failure. Although there are some drugs on the market that indirectly act on AD, their efficacy is very low and the side effects are substantial, so there is an urgent need to develop a new strategy for the treatment of AD. An increasing number of studies have confirmed epigenetic changes in AD. Although it is not clear whether these epigenetic changes are the cause or result of AD, they provide a new avenue of treatment for medical researchers worldwide. This article summarizes various epigenetic changes in AD, including DNA methylation, histone modification and miRNA, and concludes that epigenetics has great potential as a new target for the treatment of AD.

Glycyrrhiza uralensis contains many secondary metabolites with a wide range of pharmacological activities. Drought stress acts as a positive regulator to stimulate the production of medicinal active component in G. uralensis, however, the underlying mechanism remains unclear. The aim of this work is to investigate the accumulation and regulatory mechanism of pharmaceutical active ingredients in G. uralensis under drought stress. The materials of the aerial and underground parts of G. uralensis seedlings treated by 10% PEG6000 for 0, 2, 6, 12, and 24 h were used for RNA sequencing and determination of phytohormones and pharmaceutical active ingredients. PEG6000, ibuprofen (IBU), and jasmonic acid (JA) were utilized to treat G. uralensis seedlings for content detection and gene expression analysis. The results showed that, the contents of glycyrrhizic acid, glycyrrhetinic acid, and flavonoids (licochalcone A, glabridin, liquiritigenin, isoliquiritigenin, and liquiritin) were significantly accumulated in G. uralensis underground parts under drought stress. Kyoto Encyclopedia of Genes and Genomes analysis of the transcriptome data of drought-treated G. uralensis indicated that up-regulated differentially expressed genes (UDEGs) involved in glycyrrhizic acid synthesis in the underground parts and flavonoids synthesis in both aerial and underground parts were significantly enriched. Interestingly, the UDEGs participating in jasmonic acid (JA) signal transduction in both aerial and underground parts were discovered. In addition, JA content in both aerial and underground parts under drought stress showed the most significantly accumulated. And drought stress stimulated the contents of JA, glycyrrhizic acid, and flavonoids, coupled with the induced expressions of genes regulating the synthesis and transduction pathway. Moreover, In PEG6000- and JA-treated G. uralensis, significant accumulations of glycyrrhizic acid and flavonoids, and induced expressions of corresponding genes in these pathways, were observed, while, these increases were significantly blocked by JA signaling inhibitor IBU. JA content and expression levels of genes related to JA biosynthesis and signal transduction were also significantly increased by PEG treatment. Our study concludes that drought stress might promote the accumulation of pharmaceutical active ingredients via JA-mediated signaling pathway, and lay a foundation for improving the medicinal component of G. uralensis through genetic engineering technology.

Background: We aimed to investigate the demographic situation relating to people with hearing loss in Xinjiang, the largest province in China. The situation may vary between regions and races. Methods: We conducted a population-based demographic study. We analyzed data obtained from 3931 people with hearing impairments (i.e., from the Han or Uyghur ethnic groups) including children and adults. We accounted for the survey design and sampling size in order to ensure that estimates were regionally representative. Basic characteristics were determined, and an ethnic distribution analysis was conducted based on age group, level of educational, marital status, and level of disability. Results: Of the 3931 participants, 2228 (56.68%) were male and 1703 (43.32%) were female. The mean age of the participants was 46.02 (±19.46) years. Most of the participants (26.20%) were in the 45–59 yr age group. Illiterate people constituted the largest group (34.19%) in the Uyghur population, while a substantial proportion of participants of Han nationality had obtained a junior education (28.98%). The number of unmarried people in both ethnic groups accounted for the highest proportion (more than 70%). Grade 3 was the highest grade observed in the Uyghur population (32.35%), while Grade 1 hearing impairments were the most prevalent in the Han population (28.28%). Conclusion: The difference in basic characteristics between participants of Uyghur and Han ethnicity revealed that different provinces should set different prevention and control targets. Different policy measures should be taken to allocate medical resources and provide rehabilitation services to assist people with hearing impairments in Xinjiang, China. Abbreviations: WHO=World Health Organization, Xinjiang=Xinjiang Uyghur Autonomous Region, YLD=years lived with disability, dB HL=Decibel Hearing Level, SPSS=Statistical Product and Service Solutions, Inc.=Incorporated, IL=Illinois, USA=United States of America; i.e.,=id est (in other words).

Non-alcoholic fatty liver disease (NAFLD) is a common serious health problem worldwide, which lacks efficient medical treatment. We aimed to develop and validate the machine learning (ML) models which could be used to the accurate screening of large number of people. This paper included 304,145 adults who have joined in the national physical examination and used their questionnaire and physical measurement parameters as model's candidate covariates. Absolute shrinkage and selection operator (LASSO) was used to feature selection from candidate covariates, then four ML algorithms were used to build the screening model for NAFLD, used a classifier with the best performance to output the importance score of the covariate in NAFLD. Among the four ML algorithms, XGBoost owned the best performance (accuracy = 0.880, precision = 0.801, recall = 0.894, F-1 = 0.882, and AUC = 0.951), and the importance ranking of covariates is accordingly BMI, age, waist circumference, gender, type 2 diabetes, gallbladder disease, smoking, hypertension, dietary status, physical activity, oil-loving and salt-loving. ML classifiers could help medical agencies achieve the early identification and classification of NAFLD, which is particularly useful for areas with poor economy, and the covariates' importance degree will be helpful to the prevention and treatment of NAFLD.

Abstract Background Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a key mechanism in pulmonary arterial hypertension (PAH). Serotonin (5-hydroxytryptamine, 5-HT) can induce abnormal proliferation of PASMCs. The role of miR-361-3p in serotonin-induced abnormal PASMCs proliferation remains unclear. Methods The miR-361-3p level was analyzed in plasma from PAH patients and normal controls and in human PASMCs (hPASMCs) using RT-PCR. The hPASMCs were transfected with an miR-361-3p mimic and then treated with serotonin. Untransfected hPASMCs were used as the control. Cell proliferation was evaluated using an MTS assay and 5-ethynyl-2′-deoxyuridine (EdU) staining. The cell cycle stages were evaluated using flow cytometry. The association between miR-361-3p and serotonin transporter (SERT) was determined using a luciferase reporter assay and anti-AGO2 RNA immunoprecipitation assay. The protein expression was evaluated via western blotting. Results The miR-361-3p level was lower in plasma from PAH patients than in plasma from the any of the normal control subjects. The mean pulmonary arterial pressure, pulmonary vascular resistance and pulmonary vascular resistance index were higher in PAH patients whose miR-361-3p level was lower than the median value for patients than in those whose miR-361-3p level was higher than the median. Serotonin treatment reduced miR-361-3p expression in the hPASMCs. MiR-361-3p overexpression suppressed cell proliferation, promoted apoptosis, induced G1 arrest, and decreased the phosphorylation level of ERK1/2 in serotonin-treated hPASMCs. SERT was identified as an miR-361-3p target. Its overexpression alleviated the effect of miR-361-3p overexpression on serotonin-induced hPASMC proliferation and upregulation of phosphorylated ERK1/2. Conclusions The miR-361-3p level is lower in the plasma of PAH patients. Upregulation of miR-361-3p suppresses serotonin-induced proliferation of hPASMCs by targeting SERT. Our results suggest that miR-361-3p is a potential therapeutic target in PAH.

This study aims to provide valuable insight into the irrigation in curved root canals with CFD method. Numerical simulation of the flow originated from a side-vented or an open-ended flat needle located in the prepared root canal with two different insertion depths was performed. The distribution of velocity, wall shear stress, apical pressure, and the detailed flow structures were all evaluated. The results show that both the side port of the side-vented needle and the curved portion of the target root canal tends to make circumferentially non-symmetric wall shear stress distribution and asymmetrical streamlines. However, the impact of the root-canal curvature variation on the flow pattern is apparent only when the open-ended flat needle was selected for irrigation or the needle was inserted into the curved part of the root canal. The insertion depth and the size of the gap between the outer surface of the needle and the root canal internal wall are critical to the apical pressure, except the former is simultaneously crucial for the micro-velocity zone decreasing. Overall, the optimal method for effective irrigation in a curved root canal is the side-vented needle with the same curvature to the root canal, deeper insertion, and reasonable gap size.

Fluorescence spectroscopy attracted more and more attention in pesticide residue detection field because of its advantages of non-destructive, non-contact, high speed and no requirement of complex pre-process procedure. However, given that the concentration of the pesticide detected via fluorescence spectroscopy is calculated in accordance with the Beer-Lambert law, this method can only be used to detect samples containing a single kind of pesticide or several kinds of pesticides with completely different fluorescence which is not in accordance with practical cases. In this article, to overcome this disadvantage, back-propagation (BP) neural network algorithm was introduced to detect multiple kinds of pesticides via fluorescence spectroscopy. The results from four kinds of pesticides which are usually used for fruits and vegetables indicated the effectiveness of BP neural network algorithm.

Abstract Background Hantaviruses are important zoonotic pathogens, and they pose a profound risk to public health. So far, there has been no evidence showing that Tula virus (TULV), one species of hantavirus, is endemic in China. In this study, we captured rodents and found that the Tula virus had infected voles in Yili region, Xinjiang, China. Methods Rodents were captured by flooding their burrows in mountain pasture areas in Narati, Xinyuan County, Xinjiang, China. Hantavirus L gene fragments were amplified by nest RT-PCR using genus-specific primers. Positive samples were further identified by sequencing of RT-PCR products of S gene fragment for species identification. To identify the species of captured small mammals, the rodents’ cytochrome b (Cytb) was amplified by PCR and sequenced. Phylogenetic analysis was used to show the clustering and evolution relationship of the viral nucleic acids. Results Here, 31 out of 198 voles captured (16%) were infected with TULV. Host sequencing analysis showed these voles were Microtus obscurus (M. obscurs). Alignment and phylogenetic analysis of the exon region (1191 bp) of the hantavirus S gene confirmed that all of the detected amplicons were TULV, which was similar to one strain of TULV identified in Kazakhstan. Conclusion This is the first identification of Tula virus in China, and we found that M. obscurus acts as a natural reservoir for carrying the virus. Although the infection rate in the local human population remains unknown, the high prevalence of TULV in the small mammals in the region constitutes a risk that this putative pathogen may spread to the local population.

Abstract Background Polymorphisms have been identified to predispose to NAFLD. Here, we accessed the seven polymorphisms of rs1260326, rs780094 in GCKR, rs2954021 near TRIB1, rs2228603 in NCAN, rs58542926 in TM6SF2, rs12137855 near LYPLAL1, and rs10883437 near CPN1 on NAFLD susceptibility in the Uygur population. Material and methods We collected 620 samples (317 NAFLD and 303 controls) for this case-control study. Meta-analysis was performed using Stata Software. Results Our data detected that the rs1260326 (T vs. C: OR = 1.27, 95% CI = 1.01–1.59) and rs780094 (T vs. C: OR = 1.30, 95% CI = 1.04–1.63) were significantly associated with the susceptibility to NAFLD in Uygur population. The rs1260326 and rs780094 T/T genotype are significantly associated with soda, egg, and soybean intakes in the consumption group with twice or more in a week. Furthermore, a significant haplotype effect of rs1260326/T- rs780094/T was found (OR = 1.29, 95% CI: 1.03–1.62) compared with CC haplotype. An additional meta-analysis using 4352 cases and 10,168 controls established that rs780094 (OR = 1.21, 95%CI: 1.14–1.28) is significantly associated with NAFLD. Finally, among the 4 case-control studies on rs1260326, including 712 NAFLD and 658 controls, significant associations were found in Asian, liver biopsy, adult and pediatric groups. Conclusion Collectively, both our case-control study and meta-analysis confirm a significant association between rs780094 and NAFLD. Additionally, our results suggest Asian-specific, liver biopsy-specific, adult-specific and pediatric-specific associations between the rs1260326 and NAFLD. Moreover, the rs1260326 and rs780094 T/T genotype are significantly associated with food habits, such as soda, egg, and soybean.

While planning for batch manufacturing, determining the optimal runtime that minimizes total system costs is equally important and so is maintaining high product quality, keeping the batch process environment free of disruption, and ensuring timely delivery of end products to meet market demand. Owing to the imperfect nature of the fabrication process, both the production of random scrap and machine failures are inevitable and require special treatment. Permitting an acceptable level of shortages with backordering is often considered an effective approach to reduce inventory costs and lower the total system costs. Moreover, for delivering end products, a periodic multi-shipment policy is commonly adopted in real supply chain systems. To cope with the aforementioned realistic factors, this study explores a fabrication–inventory problem that considers scrap items, an acceptable level of stock outs with backordering, stochastic machine failures, and a multi-shipment policy. A mathematical model is built to accurately represent the problem. An optimization method along with an algorithm is presented to derive optimal production uptime that minimizes total system costs. Using a numerical example, we demonstrate that this precise model and its solution process can not only provide an optimal decision, but also reveal diverse and valuable system characteristics including (1) details of cost components of the system and (2) the individual and joint impact of system factors, such as product quality, service-level constraints, machine failures, number of deliveries, and uptime in the proposed problem. Without such an in-depth exploration, these important system characteristics remain inaccessible and unknown to production managers.

Purpose We aimed to assess if lipid accumulation product (LAP) could outperform body mass index (BMI) as a marker for diabetes diagnosis. Methods We analyzed the results of a national physical examination project in Urumqi, China. This project was conducted in 442 community clinics in Urumqi from October 2016 to February 2017. Results LAP was highly correlated with diabetes. The subjects with higher amounts of LAP had a higher risk of diabetes, and the prevalence of diabetes in the fourth quartile of LAP was dramatically higher than in the first quartile (5.72% vs. 21.76%). The adjusted odds ratios (AOR) associated with diabetes in the fourth quartile of LAP was significantly higher than the AOR associated with diabetes in the first quartile, and when BMI ≥ 28 kg/m2 was compared with BMI < 28 kg/m2 (3.24 (3.11, 3.37) vs. 1.65 (1.60, 1.70)). The LAP’s area under the curve (AUC) was significantly higher than the BMI’s AUC when based on diabetes (0.655 vs. 0.604). In the normal BMI group, 34% of participants had a LAP value higher than the cutoff point found during ROC analysis. In this subgroup, we observed a significantly higher prevalence of diabetes that was similar to that of the subgroup with a BMI ≥ 28 kg/m2, and both of their LAP values were higher than the cutoff point. Conclusion When use as a tool for diabetes diagnosis, LAP performed better than BMI, implying that LAP could be a preferable anthropometry assessment.

ObjectivesCompared with unaffected individuals, patients with type 2 diabetes (T2DM) have higher risk of hypertension, and diabetes combined with hypertension can lead to server cardiovascular disease. Therefore, the purpose of this study was to establish a simple nomogram model to identify the determinants of hypertension in patients with T2DM and to quickly calculate the probability of hypertension in individuals with T2DM.Materials and methodsA total of 643,439 subjects participating in the national physical examination has been recruited in this cross-sectional study. After excluding unqualified subjects, 30,507 adults with T2DM were included in the final analysis. 21,355 and 9,152 subjects were randomly assigned to the model developing group and validation group, respectively, with a ratio of 7:3. The potential risk factors used in this study to assess hypertension in patients with T2DM included questionnaire investigation and physical measurement variables. We used the least absolute shrinkage and selection operator models to optimize feature selection, and the multivariable logistic regression analysis was for predicting model. Discrimination and calibration were assessed using the receiver operating curve (ROC) and calibration curve.ResultsThe results showed that the major determinants of hypertension in patients with T2DM were age, gender, drinking, exercise, smoking, obesity and atherosclerotic vascular disease. The area under ROC curve of developing group and validation group are both 0.814, indicating that the prediction model owns high disease recognition ability. The p values of the two calibration curves are 0.625 and 0.445, suggesting that the nomogram gives good calibration.ConclusionThe individualized nomogram model can facilitate improved screening and early identification of patients with hypertension in T2DM. This procedure will be useful in developing regions with high epidemiological risk and poor socioeconomic status just like Urumqi, in Northern China.

Background. An estimated 425 million people globally have diabetes, accounting for 12% of the world’s health expenditures, and the number continues to grow, placing a huge burden on the healthcare system, especially in those remote, underserved areas. Methods. A total of 584,168 adult subjects who have participated in the national physical examination were enrolled in this study. The risk factors for type II diabetes mellitus (T2DM) were identified by p values and odds ratio, using logistic regression (LR) based on variables of physical measurement and a questionnaire. Combined with the risk factors selected by LR, we used a decision tree, a random forest, AdaBoost with a decision tree (AdaBoost), and an extreme gradient boosting decision tree (XGBoost) to identify individuals with T2DM, compared the performance of the four machine learning classifiers, and used the best-performing classifier to output the degree of variables’ importance scores of T2DM. Results. The results indicated that XGBoost had the best performance (accuracy=0.906, precision=0.910, recall=0.902, F‐1=0.906, and AUC=0.968). The degree of variables’ importance scores in XGBoost showed that BMI was the most significant feature, followed by age, waist circumference, systolic pressure, ethnicity, smoking amount, fatty liver, hypertension, physical activity, drinking status, dietary ratio (meat to vegetables), drink amount, smoking status, and diet habit (oil loving). Conclusions. We proposed a classifier based on LR-XGBoost which used fourteen variables of patients which are easily obtained and noninvasive as predictor variables to identify potential incidents of T2DM. The classifier can accurately screen the risk of diabetes in the early phrase, and the degree of variables’ importance scores gives a clue to prevent diabetes occurrence.

AIM: To investigate the changes of vascular endothelial function and hemorheological indexes in patients with primary open angle glaucoma(POAG)and to analyze the risk factors of POAG. METHODS: A total of 86 cases of POAG patients were selected as the research object(observation group), and they were divided into mild group(n=27), moderate group(n=29)and severe group(n=30)according to the visual field defect, another 30 cases normal healthy volunteers were selected as the control group. The levels of vascular endothelial function and blood hemorheology between the groups were compared, and to analysis the risk factors of the disease. RESULTS: The results of single factor analysis showed that there was no significant difference in the sex ratio, average age, history of alcoholism and cardiovascular disease between the control group and the observation group(P>0.05); the smoking history, hypertension history, diabetes history, and family history were statistically significant(PPPPPCONCLUSION: There are endothelial dysfunction and hemorrheology abnormality in patients with POAG. Smoking history, hypertension history, diabetes history, family history are related to the occurrence of POAG.

This study explores a finite production rate (FPR) model featuring overtime option and rework of nonconforming products. Classic FPR model assumed all items produced are of perfect quality. However, in real fabrication systems, owing to diverse uncontrollable conditions, production of nonconforming items is inevitable. To maintain high product quality and lower production cost allow present-day’s manufacturing firms to gain competition advantage. Also, due to limited in-house capacity, to be able to smooth production schedule enables management to meet due dates and better allocate fabrication resources. Motivated by these practical issues, the present study investigates a FPR model considering overtime and rework of nonconforming items. An exact model is developed to specifically describe the problem. Mathematical analysis and differential calculus are employed to help obtain the expected system cost function and prove its convexity, and then derive the optimal lot size per replenishment cycle. Moreover, sensitivity analysis and diverse effects of key system factors on the problem are demonstrated via numerical illustrations to help managerial decision-making. Keywords: Industrial engineering, Manufacturing system, Optimization, Finite production rate model, Overtime, Rework

Abstract Background A simple noninvasive model to predict obstructive coronary artery disease (OCAD) may promote risk stratification and reduce the burden of coronary artery disease (CAD). This study aimed to develop pre-procedural, noninvasive prediction models that better estimate the probability of OCAD among patients with suspected CAD undergoing elective coronary angiography (CAG). Methods We included 1262 patients, who had reliable Framingham risk variable data, in a cohort without known CAD from a prospective registry of patients referred for elective CAG. We investigated pre-procedural OCAD (≥50% stenosis in at least one major coronary vessel based on CAG) predictors. Results A total of 945 (74.9%) participants had OCAD. The final modified Framingham scoring (MFS) model consisted of anemia, high-sensitivity C-reactive protein, left ventricular ejection fraction, and five Framingham factors (age, sex, total and high-density lipoprotein cholesterol, and hypertension). Bootstrap method (1000 times) revealed that the model demonstrated a good discriminative power (c statistic, 0.729 ± 0.0225; 95% CI, 0.69–0.77). MFS provided adequate goodness of fit (P = 0.43) and showed better performance than Framingham score (c statistic, 0.703 vs. 0.521; P

Objective: Stroke is the leading cause of death and disability, and is closely related to a lack of exercise. Currently, most Chinese medical staff members lack exercise and may be at risk for stroke. We sought to determine the risk factors for stroke and study the significance of health-related physical fitness testing in stroke prevention among Chinese medical staff members. Methods: A total of 627 subjects from Urumqi, Xinjiang, China, were included in the study and a survey was conducted from 1st January 2016 to 1st February 2016. Stroke screening and health-related physical fitness testing were completed according to the standard protocol, and the related data were analyzed. Results: Based on the screening, 27.6% (n = 173) of the subjects were at high risk for stroke. The top risk factors for stroke in these subjects were dyslipidemia, lack of exercise or mild physical activity, being overweight or obese, and high blood pressure. Body weight, body mass index, body fat, visceral fat area, body fat percentage, and basal metabolic rate were significantly higher (P

Abstract Background The role of 1,25-dihydroxyvitamin D3 (vitamin D) in the apoptosis of diabetic cardiomyopathy (DCM) is unclear. This study is to investigate the effects of vitamin D on the pathological changes in rats with DCM. Methods Rats were randomly divided into the control, model, and treatment groups. DCM model was established by the high-fat and -sugar diet. Plasma glucose, body weight, heart weight, heart weight index, and serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were determined. Heart tissue morphology was detected with histochemical staining. Expression levels of Fas and FasL were detected with RT-PCR and immunohistochemistry. Results Compared with the control group, the body weights and heart weights were significantly declined, while the plasma glucose levels and heart weight indexes were significantly elevated, in the model group (P

Circular RNAs have continuous, stable, and covalently closed circular structures and are not easily degraded by nucleases, thus they are ideal serum biomarkers for detecting diseases. However, research is still lacking on circular RNAs as diagnostic and prognostic markers for idiopathic pulmonary arterial hypertension. This study investigated the potential role of serum circ_0068481 levels in idiopathic pulmonary arterial hypertension diagnosis and prognosis. This prospective cohort study enrolled 82 patients with idiopathic pulmonary arterial hypertension between January 2016 and July 2018 at Guangdong Provincial People’s Hospital. Serum circ_0068481 levels were measured using quantitative reverse transcription-polymerase chain reaction. Baseline data, including clinical background, hemodynamic variables, and biochemical variables, were collected. Receiver operating characteristic curves were used to investigate diagnostic effect, the Kaplan–Meier method was used to estimate survival rates, and univariate analysis of prognostic factors was performed with a Cox proportional hazard model. We found that serum circ_0068481 expression levels were significantly higher in patients with idiopathic pulmonary arterial hypertension and had higher sensitivity and specificity for predicting idiopathic pulmonary arterial hypertension. Additionally, we found that circ_0068481 expression correlated significantly with heart function, 6-min walk distance, serum N-terminal pro-B-type natriuretic peptide, serum H 2 S, the 6th World Symposium on Pulmonary Hypertension risk stratification, right heart failure, and patient death. Moreover, serum circ_0068481 levels were elevated in patients with idiopathic pulmonary arterial hypertension and right heart failure and were able to predict right heart failure. Serum circ_0068481 levels were also elevated in patients who died with idiopathic pulmonary arterial hypertension and were able to predict poorer clinical outcomes. Circ_0068481 is a novel and noninvasive biomarker for diagnosing idiopathic pulmonary arterial hypertension and predicting poor clinical outcome in patients with idiopathic pulmonary arterial hypertension.

Hyperforin has been shown to be capable of promoting angiogenesis and functional recovery after ischemic stroke in our previous study. However, the exact mechanisms involved are not fully elucidated. In this study, adult male mice were subjected to 60-min transient middle cerebral artery occlusion followed by reperfusion for 28 days. Hyperforin was administrated to MCAO mice every 24 h for 2 weeks starting at 14 days post-ischemia (dpi). Then flow cytometry, quantitative Real-time PCR (RT-qPCR), western blotting, immunohistochemistry, and functional assays were performed to explore the molecular mechanisms in vivo and in vitro. Our data showed that hyperforin increased astrocytic interleukin (IL)-6 in the ischemic hemisphere via TLR4 at 28 dpi. The astrocytic IL-6 was essential to the promoting effects of hyperforin on the neural precursor cells proliferation, neuronal differentiation, angiogenesis, and functional recovery after stroke. Furthermore, hyperforin promoted the infiltration of regulatory T cells (Tregs) to the ischemic hemisphere and increased Tregs-derived cytokine IL-10 and transforming growth factor-β (TGF-β) in a manner that was dependent on astrocytic IL-6. Astrocytic IL-6 was critical to the role of hyperforin in promoting the infiltration of T-helper (Th) type 2 cells to the ischemic hemisphere and Th2-derived cytokine IL-4, relative to Th1 and Th1-derived cytokine interferon-γ (IFN-γ), which decreased during stroke recovery. After depletion of CD25+ Tregs, the promoting effects of hyperforin on post-stroke neurogenesis was attenuated. Moreover, blockade of IL-4 and TGF-β abrogated the promoting role of hyperforin in post-stroke neurogenesis, angiogenesis and functional recovery. Our results reveal a previously uncharacterized role of astrocytic IL-6-mediated negative immune regulation in the promoting effects of hyperforin on post-stroke neurovascular regeneration and functional recovery.

The purpose of this study was to develop mixed polymeric micelles with high drug loading capacity to improve the oral bioavailability of icaritin with Soluplus® and Poloxamer 407 using a creative acid-base shift (ABS) method, which exhibits the advantages of exclusion of organic solvents, high drug loading and ease of scaling-up. The feasibility of the ABS method was successfully demonstrated by studies of icaritin-loaded polymeric micelles (IPMs). The prepared IPMs were characterized to have a spherical shape with a size of 72.74 ± 0.51 nm, and 13.18% drug loading content. In vitro release tests confirmed the faster release of icaritin from IPMs compared to an oil suspension. Furthermore, bioavailability of icaritin in IPMs in beagle dogs displayed a 14.9-fold increase when compared with the oil suspension. Transcellular transport studies of IPMs across Caco-2 cell monolayers confirmed that the IPMs were endocytosed in their intact forms through macropinocytosis, clathrin-, and caveolae-mediated pathways. In conclusion, the results suggested that the mixed micelles of Soluplus® and Poloxamer 407 could be a feasible drug delivery system to enhance oral bioavailability of icaritin, and the ABS method might be a promising technology for the preparation of polymeric micelles to encapsulate poorly water-soluble weakly acidic and alkaline drugs.

Icaritin is a promising anti-hepatoma drug that is currently being tested in a phase-III clinical trial. A novel combination of amorphization and nanonization was used to enhance the oral bioavailability of icaritin. Amorphous icaritin nanoparticles (AINs) were prepared by a reactive precipitation technique (RPT). Fourier transform infrared spectrometry was used to investigate the mechanism underlying the formation of amorphous nanoparticles. AINs were characterized via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Our prepared AINs were also evaluated for their dissolution rates in vitro and oral bioavailability. The resultant nanosized AINs (64 nm) were amorphous and exhibited a higher dissolution rate than that derived from a previous oil-suspension formulation. Fourier transform infrared spectroscopy (FTIR) revealed that the C=O groups from the hydrophilic chain of polymers and the OH groups from icaritin formed hydrogen bonds that inhibited AIN crystallization and aggregation. Furthermore, an oral administration assay in beagle dogs showed that Cmax and AUClast of the dried AINs formulation were 3.3-fold and 4.5-fold higher than those of the oil-suspension preparation (p < 0.01), respectively. Our results demonstrate that the preparation of amorphous drug nanoparticles via our RPT may be a promising technique for improving the oral bioavailability of poorly water-soluble drugs.

Background: Rare ginsenosides in Panax quinquefolius L. have strong bioactivities. The fact that it is hard to obtain large amounts of rare ginsenosides seriously restricts further research on these compounds. An easy, fast, and efficient method to obtain different kinds of rare ginsenosides simultaneously and to quantify each one precisely is urgently needed. Methods: Microwave-assisted extraction (MAE) was used to extract nine kinds of rare ginsenosides from P. quinquefolius L. In this article, rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5] were identified by high performance liquid chromatography (HPLC)–electrospray ionization–mass spectrometry. The quantity information of rare ginsenosides was analyzed by HPLC-UV at 203 nm. Results: The optimal conditions for MAE were using water as solvent with the material ratio of 1:40 (w/v) at a temperature of 145°C, and extracting for 15 min under microwave power of 1,600 W. Seven kinds of rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, Rk1, and Rg5] had high extraction yields, but those of 20(S)-Rg3 and 20(R)-Rg3 were lower. Compared with the conventional method, the extraction yields of the nine rare ginsenosides were significantly increased. Conclusion: The results indicate that rare ginsenosides can be extracted effectively by MAE from P. quinquefolius L. in a short time. Microwave radiation plays an important role in MAE. The probable generation process of rare ginsenosides is also discussed in the article. It will be meaningful for further investigation or application of rare ginsenosides.

Background. Despite a rapid popular of early onset type 2 diabetes (defined as diagnosis at