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Rab11‑family interacting proteins (Rab11‑FIPs) are associated with the progression of various tumors; however, their expression and clinical significance in colorectal cancer (CRC) remains largely undetermined. In this study, the clinical implications, functions and underlying mechanisms of Rab11‑FIP4 in CRC were investigated. Immunohistochemical analysis revealed that expression of Rab11‑FIP4 was significantly increased in human CRC tissues and correlated with poor prognosis of patients with CRC. Overexpression of Rab11‑FIP4 in the CRC cell line significantly promoted cell proliferation, migration and invasion in vitro and tumor metastasis in vivo. Furthermore, the results of a co‑immunoprecipitation assay and western blot analysis demonstrated that Rab11‑FIP4 interacted with Rab11 and insulin‑like growth factor 1 receptor, and increased the phosphorylation of extracellular signal‑regulated kinase 1/2 and AKT serine/threonine kinase. In addition, hypoxia contributed to the upregulation of Rab11‑FIP4 expression via hypoxia‑inducible factor‑1α activation of the Rab11‑FIP4 promoter. In conclusion, the results of the present study suggest that Rab11‑FIP4 may act as an oncogene in CRC, and may be a potential therapeutic target for the treatment of patients with CRC. [ABSTRACT FROM AUTHOR]

Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells. In this study, we aimed to investigate the function of autophagy as well as its upstream and downstream signals in cigarette smoke-induced mucus production in human bronchial epithelial (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the classical autophagy inducers starvation or Torin-1, significantly triggered MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced mucus production. The CSE-induced autophagy was mediated by mitochondrial reactive oxygen species (mitoROS), which regulated mucin expression through the JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable effects on the autophagy-JNK signaling cascade. Airways of mice with dysfunctional autophagy-related genes displayed a markedly reduced number of goblet cells and attenuated levels of Muc5ac in response to cigarette smoke exposure. These results altogether suggest that mitoROS-dependent autophagy is essential for cigarette smoke-induced mucus hyperproduction in airway epithelial cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for chronic airway diseases. [ABSTRACT FROM AUTHOR]

Alternative Binary Offset Carrier (AltBOC) modulation signal has the constraint of an equal power allocation scheme. Thus, it is not flexible enough to meet different requirements. To solve this problem, we propose a General AltBOC (GAltBOC) modulation. The proposed technique can achieve the same function as AltBOC. Meanwhile, its power allocation ratio can be adjusted when required. The detailed derivation of the GAltBOC modulation is presented, and three representative cases as well as the signal properties are discussed. To further improve the combination efficiency, we develop the Interlacing GAltBOC (IGAltBOC) modulation based on the GAltBOC modulation. The Power Spectrum Density (PSD) and correlation functions of the proposed signals are verified by simulation. The code tracking error and implementation complexities are analysed and compared with existing methods. Results show the proposed signals indeed enhance the flexibility of power allocation ratio with the same level code tracking accuracy. Compared with AltBOC modulation, the proposed signal can reach a higher combination efficiency at the expense of relatively higher implementation complexity. Compared with Asymmetric Constant Envelope Double-sideband (ACED) modulation, the proposed signals have significantly lower complexity of signal generation, which is helpful in simplifying the signal generation in the payload transmitter. [ABSTRACT FROM AUTHOR]

In this paper, two novel anti-unwinding constrained attitude controllers for flexible spacecraft are designed based on inverse optimal approach and unit quaternion representation of attitude subjected to inertia matrix uncertainty and external disturbance. One accounts for actuator amplitude constraint and the other considers actuator amplitude and rate constraints at length. A new saturation compensator is designed and embedded into the controllers to eliminate the effect of actuator saturation. The proposed controllers can avoid the issue of attitude slewing unwinding due to the double values of unit quaternions. The stability of the resulting closed-loop systems by the proposed controllers is guaranteed by Lyapunov-based approach. Simulation results are presented to assess the performance of the proposed methods. [ABSTRACT FROM AUTHOR]

Tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs) are difficult to differentiate between in certain clinical situations. Interleukin (IL)-33 is a cytokine that participates in inflammatory responses and may have a role in pleural effusions. The present study aimed to investigate the concentrations and potential differential significance of IL-33 in patients with TPE and MPE. IL-33 levels in pleural effusion and serum samples were detected using sandwich enzyme-linked immunosorbent assay in 23 patients with TPE and 21 patients with MPE. The concentration of IL-33 (mean ± standard deviation) in the TPE patients (22.962±0.976 ng/l) was significantly higher than that in the MPE patients (12.603±5.153 ng/l; P<0.001; z=-4.572); however, there was no significant difference in the serum level of IL-33 in the patients with TPE compared with those with MPE (P>0.05). The concentration of IL-33 in the pleural effusions was positively correlated with that in the serum samples in each group (TPE: r=0.563, P=0.05; MPE: r=0.535, P<0.05). The cut-off value of pleural IL-33 for TPE was 19.86 ng/l, which yielded a sensitivity of 0.869, a specificity of 0.905 and an area under the corresponding receiver operating characteristic curve of 0.903. The present study identified that the level of pleural IL-33 is significantly increased in TPEs and may serve as a novel biomarker to differentiate between patients with TPE and MPE. [ABSTRACT FROM AUTHOR]

The transcriptome database of the oriental fruit fly, Bactrocera dorsalis (Hendel), was used to identify the functional gene-microsatellite (EST-SSR) markers and to analyze the SSR loci information. In total, 1890 EST-SSR loci were identified, of which, 1296 SSR sequences could be used for primer design. The average distribution frequency of the transcriptomic SSRs was 1/10. 21 kb. However, these distribution frequencies varied considerably among different types of repeat SSRs. The tri-nucleotide repeat SSRs were found to have the highest frequency among the different types of repeat SSRs in the EST-SSR of B. dorsalis. Combining with other literatures, we inferred that the trinucleotide repeat SSRs were the most abundant EST-SSR in all of insects. In this study, 42 pairs of EST-SSR primers were designed and 18 pairs produced amplification bands of expected sizes. According to the results of other related literatures, the practices and challenges of strategy for SSR isolation from insect transcriptome databases were discussed, and the problems which should be considered in the screening of insect transcriptomic EST-SSR were put forward. [ABSTRACT FROM AUTHOR]

In order to explore impact of the area-road congestion charging about the residents' residential location and transportation modes, the satisfaction assessment model was proposed to assess the residential location, and the household consumption remaining model was established by the satisfaction, household income and house prices. Area-road congestion charging regimes were implemented, and the generalized commuting traffic impedance and generalized holiday entertainment traffic impedance were got by different trip purpose travel chain characteristics and the corresponding travel mode of family members. The residence of the largest family remaining was got by the household consumption remaining model. The results indicate that area-road congestion charging regimes don't affect low-income mobile home residential choice. A lower level congestion charging does not affect high-income mobile home residential choice, and a higher levels congestion charging makes high-income families mobile home residential from the suburbs to charging regional-border, and it has no affect when the charging level is high. On weekdays and holidays, there is an optimum point both the regional congestion charging level, and the holidays charging optimum point is higher, so it is conducive to maximize for economic efficiency and social utility when the best charging point is implemented. [ABSTRACT FROM AUTHOR]

Background and Aim: Nutrient production by intestinal microbiota corresponds to regulate appetite while gut microbial composition was influenced by diet ingestion. However, the causal relationship between gut microbial taxa and anorexia nervosa (AN) remains unclear. Mendelian Randomization (MR) is a novel research method that effectively eliminates the interference of confounding factors and allows for the exploration of the direct causal effects between exposure and outcome. This study employs MR to explore the causal effect between AN and specific gut microbiome., Methods: Large-scale Genome Wide Association Study (GWAS) data of AN and 211 gut microbes were obtained from the IEU open GWAS project and Mibiogen Consortium. Two-sample MR was performed to determine the causal relationship between gut microbiota and AN. Furthermore, a bi-directional MR analysis was to examine the direction of the causal relations. The Bonferroni correction test was used to adjust potential correlations among microbial taxa., Result: In forward MR analysis, 10specific gut microbial taxa have an impact on the occurrence of AN (the p value of IVW <0.05). The high abundance of Genus Eubacteriumnodatumgroup ID: 11297 (OR:0.78, 95% CI:0.62-0.98, p  = 0.035) and Class Melainabacteria ID: 1589 (OR:0.72, 95% CI:0.51-0.99, p  = 0.045) may be considered protective factors for AN. But after Bonferroni correction, only Class Actinobacteria ID:419 (OR:1.53, 95% CI:1.19-1.96, p  = 0.00089) remained significantly associated and high abundance of Class Actinobacteria ID:419 considered as a risk factor for AN. In the reverse MR analysis, AN influences 8 gut microbial taxa with none-statistically significant associations after adjustment., Conclusion: We identified a significant correlation between AN and 18 microbial taxa which have not been previously reported. Among them, 10 kinds of gut bacteria may affect the occurrence of AN, and the status of AN would affect 8 kinds of gut bacteria. After correction, the Class Actinobacteria ID:419 continued to exert an influence on AN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, He, Zhang, Wang, He, Xiao and Yang.)

Background and Aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis., Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations., Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05)., Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiao, Yang, Chen, Xie, Li, Fu, Han, Qin, Tian, Zhao, Cai, Hu, Ai, Li, Chen, Wang, Tan, Xia and Zhang.)

The sudden outbreak of monkeypox in 2022 suggests the importance of developing a rapid but sensitive virus detection technology. Herein, we report a colorimetric/surface-enhanced Raman scattering (SERS) dual-signal co-enhanced immunochromatographic assay (ICA) for the flexible, ultrasensitive, and accurate detection of monkeypox virus (MPXV) in various complex samples. A thickness-controlled polyethyleneimine interlayer (1 nm) is coated onto two-dimensional molybdenum disulfide (MoS 2 ) nanosheet to enable the electrostatic adsorption of two layers of dense 30 nm AuNPs, which not only improves colorimetric ability but also creates numerous efficient SERS hotspots. Moreover, the SERS activity of film-like dual-signal tag (MoS 2 @Au-Au) is drastically enhanced by combining the chemical enhancement effect of MoS 2 sheets and the electromagnetic enhancement effect of Au-Au hotspots. The introduction of MoS 2 @Au-Au greatly broadens the application range of existing ICA methods, in which the colorimetric signal supports the quick identification of the target virus and the SERS signal allows the quantitative detection of MPXV with detection limits of as low as 0.2 and 0.002 ng/mL. Given its rapid detection ability (< 20 min), high accuracy in real samples (RSD < 9.89 %), and superior sensitivity than traditional AuNP-based colorimetric ICA (> 500 times), the proposed assay has great potential for field application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the association between serum magnesium trajectory and risk of in-hospital mortality in intensive care unit (ICU) patients with sepsis. Adult sepsis patients who had complete data on serum magnesium at ICU admission (at 0, 12, 24, 36 and 48 hours after ICU admission) based the 2012-2019 Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included in this retrospective cohort study. Serum magnesium trajectories were identified using K-means cluster analysis. The multivariable Cox proportional-hazards model was used to evaluate the association between magnesium level at different time points or magnesium trajectory and in-hospital mortality. A total of 2,270 patients with sepsis were enrolled, and in-hospital mortality occurred in 716 (31.54%). Three trajectories were identified: a high-level declining trajectory, normal-level stable trajectory, and low-level rising trajectory. Among the magnesium levels at different time points, a higher serum magnesium level only at ICU admission (0h) (hazard ratio [HR] = 1.13, 95% confidence interval [CI]: 1.03-1.23) was associated with an increased risk of in-hospital mortality. Compared with the normal-level stable trajectory group, patients in the low-level rising trajectory group (HR = 0.82, 95%CI: 0.70-0.97) had a reduced risk of in-hospital mortality, but no association with in-hospital mortality was found in patients in the high-level declining trajectory group (p=0.812). Conclusion: Sepsis patients with a low-level, rising magnesium trajectory may have a reduced risk of in-hospital mortality.

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Xia, He, Xiao, Wang, Huang and Zhang.)

Fast and sensitive identification of foodborne bacteria in complex samples is the key to the prevention and control of microbial infections. Herein, an ultrasensitive lateral flow assay (LFIA) based on multilayered fluorescent nanofilm (GO/DQD)-guided signal amplification was developed for the rapid and quantitative determination of Salmonella typhimurium ( S. typhi ). The film-like GO/DQD was prepared through the electrostatic mediated layer-by-layer assembly of numerous carboxylated CdSe/ZnS quantum dots (QDs) onto an ultrathin graphene oxide (GO) nanosheet, which possessed advantages including higher QD loading, larger surface areas, superior luminescence, and better stability, than traditional spherical nanomaterials. The antibody-modified GO/DQD can effectively attach onto a target bacterial cell to form a GO/DQD-bacteria immunocomplex containing almost ten thousand QDs, thus greatly improving the detection sensitivity of LFIA. The constructed GO/DQD-LFIA biosensor achieved the rapid and sensitive detection of S. typhi in 14 min with detection limits of as low as 9 cells/mL. Moreover, compared with traditional LFIA techniques for bacteria detection, the proposed assay exhibited excellent stability and accuracy in real food samples and enormously improved sensitivity (2-3 orders of magnitude), demonstrating its great potential in the field of rapid diagnosis.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

PEGylation is a well-established technology for half-life extension in drug delivery. In this study, we aimed to develop a site-specific N-terminal PEGylation for biotherapeutics to achieve controlled release, using GLP-1 as a model. An additional threonine was introduced at N-terminal GLP-1. Followed by periodate oxidation, hydrazide-based PEGylation was achieved in a site-selective manner under reductive condition. Two homogenous monovalent mPEG 5k -GLP-1 (peptide 4) and mPEG 20k -GLP-1 (peptide 5) were successfully constructed. After PEGylation, the degradation by DPP-IV and rat plasma was obviously reduced. Their pharmacokinetic performances were enhanced at the expense of impaired GLP-1R stimulating potency, and their hypoglycemic effects were improved in different degrees. Compared with conventional strategies, this approach is devoid of the restriction and alteration of native peptide sequences, and can produce utterly homogenous conjugates with excellent selectivity and efficiency. It provides a practical controlled release approach for peptides by site-specific modification to achieve better pharmacological and therapeutic properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Hyperglycemia and hypoglycemia are common during coronary artery bypass graft (CABG) and are associated with a variety of postoperative outcomes. Therefore, the strategy of intraoperative glycemic control is an important issue for the patients undergoing CABG. This systematic review aims to evaluate the effect of different intraoperative glycemic control strategies on postoperative outcomes., Methods and Analyses: We will perform this systematic review of randomised controlled trials (RCTs) according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies will be searched in Medline, Embase, Cochrane Library and Web of Science. Two independent reviewers will conduct study selection, data extraction, risk of bias and quality assessment. The primary outcome is postoperative mortality, and the secondary outcomes include the duration of mechanical ventilation in the intensive care unit (ICU), the incidence of postoperative myocardial infarction (MI), the incidence of postoperative atrial fibrillation (AF), the type and volume of blood product transfusion, the rate of rehospitalization, the rate of cerebrovascular accident, the rate of significant postoperative bleeding, the rate of infection, the incidence of acute kidney failure (AKF), hospital and ICU lengths of stay (LOS). ReviewManager 5.4 will be used for data management and statistical analysis. The Cochrane risk-of -bias tool 2.0 and GRADEpro will be applied for risk of bias and quality assessment of the evidence., Discussion: There is no consensus that which strategy of glycemic control is better for improving postoperative complications of patients undergoing CABG. The results of our study might provide some evidence for the relationship between intraoperative glycemic control strategies and postoperative outcomes in patients undergoing CABG., Competing Interests: The authors have declared that no competing interests exist.

IKKε (inhibitor of nuclear factor kappa-B kinase ε) is a member of the noncanonical NF-κB pathway. It participates in the inflammatory response and innate immunity against bacteria. In recent decades, IKKε has been closely associated with metabolic regulation. Inhibition of the IKKε pathway can improve fat deposition in the liver, reduce subcutaneous fat inflammation, and improve liver gluconeogenesis in obesity. IKKε is expected to be a new therapeutic target for metabolic diseases such as nonalcoholic fatty liver disease, diabetes, and obesity. Herein, we summarize the structural characterization, physiological function, and pathological role of IKKε in metabolic diseases and small molecule inhibitors of IKKε., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, He, Li, Song, Chen, Zeng and Xia.)

Growth and differentiation factor 15 (GDF-15) was discovered as a member of the transforming growth factor β (TGF-β) superfamily and the serum level of GDF-15 was significantly correlated with glucolipid metabolic disorders (GLMD) and cardiovascular diseases. In 2017, a novel identified receptor of GDF-15-glial-derived neurotrophic factor receptor alpha-like (GFRAL) was found to regulate energy homeostasis (such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD)). The function of GDF-15/GFRAL in suppressing appetite, enhancing glucose/lipid metabolism and vascular remodeling has been gradually revealed. These effects make it a potential therapeutic target for GLMD and vascular diseases. In this narrative review, we included and reviewed 121 articles by screening 524 articles from literature database. We primarily focused on the function of GDF-15 and its role in GLMD/cardiovascular diseases and discuss its potential clinical application., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The safety issues like immunogenicity and unacceptable cancer risk of viral vectors for DNA/mRNA vaccine delivery necessitate the development of non-viral vectors with no toxicity. Among the non-viral strategies, cell-penetrating peptides (CPPs) have been a topic of interest recently because of their ability to cross plasma membranes and facilitate nucleic acids delivery both in vivo and in vitro. In addition to the application in the field of gene vaccine and gene therapy, CPPs based nucleic acids delivery have been proved by its potential application like gene editing, RNA-sequencing, and imaging. Here, we focus on summarizing the recent applications and progress of CPPs-mediated nucleic acids delivery and discuss the current problems and solutions in this field., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dexamethasone is widely used to treat preterm labor and related diseases. However, prenatal dexamethasone treatment (PDT) can cause multiorgan developmental toxicities in offspring. Our previous study found that the occurrence of fetal-originated diseases was associated with adrenal developmental programming alterations in offspring. Here, we investigated the effects of PDT on adrenal function in offspring and its intrauterine programming mechanism. A rat model of PDT was established to observe the alterations of adrenal steroidogenesis in offspring. Furthermore, we confirmed the sex differences of adrenal steroidogenesis and its molecular mechanism combined with in vivo and in vitro experiments. PDT caused a decrease in adrenal steroidogenic function in fetal rats, but it was decreased in males and increased in females after birth. Meanwhile, the adrenal H3K14ac level and expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) in PDT offspring were decreased in males and increased in females, suggesting that 11β-HSD2 might mediate sex differences in adrenal function. We further confirmed that dexamethasone inhibited the H3K14ac level and expression of 11β-HSD2 through the GR/SP1/p300 pathway. After bilateral testectomy or ovariectomy of adult PDT offspring rats, adrenal 11β-HSD2 expression and steroidogenic function were both reduced. Using rat primary fetal adrenal cells, the differential expression of AR and ERβ was proven to be involved in regulating the sex difference in 11β-HSD2 expression. This study demonstrated the sex difference in adrenal steroidogenic function of PDT offspring after birth and elucidated a sex hormone receptor-dependent epigenetically regulating mechanism for adrenal 11β-HSD2 programming alteration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We previously found that prenatal ethanol exposure (PEE) induced adrenal dysplasia in offspring, which was related to intrauterine maternal glucocorticoid overexposure. This study investigated the intergenerational genetic effect and sex differences of PEE-induced changes in the synthetic function of adrenal corticosterone in offspring, and to clarify the intrauterine origin programming mechanism. Wistar pregnant rats were gavaged with ethanol (4 g/kg bw/d) from gestation day (GD) 9-20, and F1 generation was born naturally. The F1 generation female rats in the PEE group were mated with normal male rats to produce F2 generation. Serum and adrenal glands of fetal rats and F1/F2 adult rats were collected at GD20 and postnatal week 28. PEE increased the serum corticosterone level, while diminishing the expression of adrenal steroid synthases of fetal rats. Moreover, PEE enhanced the mRNA expression of GR and HDAC1, but inhibited the mRNA expression of SF1 and reduced the H3K9ac level of P450scc in the fetal adrenal gland. In PEE adult offspring of F1 and F2 generation the serum corticosterone level, the H3K9ac level of P450scc and its expression were decreased in males but were increased in females. In NCI-H295R cells, cortisol reduced the production of endogenous cortisol, down-regulated SF1, and up-regulated HDAC1 expression by activating GR, and decreased H3K9ac level and expression of P450scc. In conclusion, PEE could induce adrenal dysplasia in offspring with sex differences and intergenerational genetic effects, and the adrenal insufficiency in male offspring was related to the induction of low functional genetic programming of P450scc by intrauterine high corticosterone through the GR/SF1/HDAC1 pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Heart-valve replacement is one of the main surgical methods for various heart-valve diseases. Warfarin is the only oral anticoagulant used for thrombosis prevention after heart-valve replacement. However, warfarin has a narrow therapeutic window, large differences in efficacy between individuals, and can be affected by drugs, food and disease status., Patient Concerns: We used the Hamberg model to develop an anticoagulation regimen for a 10-month-old Chinese male after mitral-valve replacement., Diagnoses: Echocardiography revealed mitral malformation with severe regurgitation, patent foramen ovale, thickening of the left ventricular wall, enlargement of the left atrium, and the overall systolic function of the left ventricle was lower than normal., Interventions: First, the patient was treated with Mitral valvuloplasty plus temporary implantation of a pacing wire. Since this was inadequate, he underwent mitral-valve replacement. Then, we used the Hamberg model to develop an anticoagulation regimen., Outcomes: After discharge from hospital, the pharmacist provided anticoagulation management for this pediatric patient using an "Online Anticoagulation Clinic" (OAC). Point-of-care testing could be employed by the boy's mother at home to obtain the International Normalized Ratio. His time to response was 89.6% during the 6 months after hospital discharge, and adverse reactions such as bleeding or thrombosis did not occur., Lessons: This is the first time the Hamberg model has been employed to design anticoagulation therapy for an Asian infant. His anticoagulation therapy may be managed using the OAC.

Crytotanshinone (CTN), one of the main constituents of Salvia miltiorrhiza, has been known to exhibit antioxdative, anti-inflammatory and other important therapeutic activities. The aim of this study was to evaluate the effect of CTN on prostaglandin E2 and COX-2 production in LPS-stimulated human intestinal cells (Caco-2 cells). Caco-2 cells were stimulated with LPS in the presence or absence of CTN. The production of prostaglandin E2 (PGE 2 ) was detected by ELISA. The expression of COX-2 was detected by qRT-PCR and Western blot. The extent of phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4 were detected by western blot. The results showed that CTN dose-dependently inhibited the expression of COX-2 both in mRNA and protein levels, resulting in a decreased production of PGE 2 . We also found that CTN suppressed LPS-induced NF-κB activation and IκBα degradation. Furthermore, CTN inhibited the expression of TLR4 up-regulated by LPS. These results suggest that CTN exerts an anti-inflammatory property by inhibiting TLR4/NF-κB signaling pathway and the release of pro-inflammatory mediators. These findings suggest that CTN may be a therapeutic agent against intestinal inflammatory diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In the Forestry Experimental Station of Shandong Agricultural University, we determined the photosynthetic physiological and biochemical indexes including photosynthetic parameters, chlorophyll fluorescence, and chlorophyll content of one-year-old poplar seedlings under different doses (0.17, 0.33, 0.67, 1.00, 1.33 and 1.67 g·kg -1 ) of Chaetomium globosmn ND35 fungus fertilizer treatment to study the effects of fungus fertilizer on photosynthesis of poplar in replanted soil. The results showed that with the increase of fungus fertilizer dose, the chlorophyll content of poplar lea-ves (Chl) showed an increasing trend, while the physiological indexes such as electron transport rate (ETR), net photosynthetic rate (P n ), quantum efficiency (Φ), nitrate reductase (NR) activity and root vigor showed an increasing first and then decreasing trend. Meanwhile, the heat dissipation that depended on xanthophyll cycle decreased and non-photochemical quenching (NPQ) increased first and then decreased. When the dose of C. globosmn ND35 fungus fertilizer was 0.67 g·kg -1 or 1.00 g·kg -1 , excess light energy of photosynthetic apparatus was reduced, and photosynthetic apparatus distributed more light energy to the direction of photochemical reactions, which improved the energy use efficiency. Applying an appropriate amount (0.67-1.00 g·kg -1 ) of C. globosmn ND35 fungus fertilizer could improve root physiological activity and light use ability of poplar leaves, which was conducive to the improvement of operating states of photosynthetic apparatus, and then increased the photosynthetic efficiency of the poplar leaves.

The transcriptome database of the oriental fruit fly, Bactrocera dorsalis (Hendel), was used to identify the functional gene-microsatellite (EST-SSR) markers and to analyze the SSR loci information. In total, 1890 EST-SSR loci were identified, of which, 1296 SSR sequences could be used for primer design. The average distribution frequency of the transcriptomic SSRs was 1/10. 21 kb. However, these distribution frequencies varied considerably among different types of repeat SSRs. The tri-nucleotide repeat SSRs were found to have the highest frequency among the different types of repeat SSRs in the EST-SSR of B. dorsalis. Combining with other literatures, we inferred that the tri-nucleotide repeat SSRs were the most abundant EST-SSR in all of insects. In this study, 42 pairs of EST-SSR primers were designed and 18 pairs produced amplification bands of expected sizes. According to the results of other related literatures, the practices and challenges of strategy for SSR isolation from insect transcriptome databases were discussed, and the problems which should be considered in the screening of insect transcriptomic EST-SSR were put forward.

The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is mainly expressed in liver and small intestine, where it plays an important role in bile acid, lipid, and glucose metabolism. The kidney also has a high FXR expression level, with its physiological function unknown. Here we demonstrate that FXR is ubiquitously distributed in renal tubules. FXR agonist treatment significantly lowered urine volume and increased urine osmolality, whereas FXR knockout mice exhibited an impaired urine concentrating ability, which led to a polyuria phenotype. We further found that treatment of C57BL/6 mice with chenodeoxycholic acid, an FXR endogenous ligand, significantly up-regulated renal aquaporin 2 (AQP2) expression, whereas FXR gene deficiency markedly reduced AQP2 expression levels in the kidney. In vitro studies showed that the AQP2 gene promoter contained a putative FXR response element site, which can be bound and activated by FXR, resulting in a significant increase of AQP2 transcription in cultured primary inner medullary collecting duct cells. In conclusion, the present study demonstrates that FXR plays a critical role in the regulation of urine volume, and its activation increases urinary concentrating capacity mainly via up-regulating its target gene AQP2 expression in the collecting ducts.

Objective: To explore the renoprotective effect of Compound Xueshuantong Capsule (XST) on diabetic rat model with nephropathy., Methods: Twenty-eight male Sprague Dawley diabetic rats were induced to hyperglycaemia (3 days later, fasting blood glucose > 16.7 mmol/L) by peritoneal injection with streptozotocin (STZ, 50 mg/kg). And they were divided into four groups: diabetic nephropathy (vehicle treatment), irbesartan (20 mg×kg(-1)×d(-1)), low-dosage XST (900 mg×kg(-1)×d(-1)) and high-dosage XST (1800 mg×kg(-1)×d(-1)). Seven normal rats were used as control. After a 12-week intervention, urine protein was examined. Pathological morphology was observed by hematoxylin-eosin (HE), Masson and (periodic acid Schiff) PAS stains. Blood nitric oxide (NO), malondialdehyde (MDA) and blood superoxide dismutase (SOD) and urine SOD were detected. And the expression of (matrix metalloproteinase-2) MMP-2 was detected by Western blot in each group., Results: The model rats presented with hyperglycemia, polydipsia, hyperphagia, polyuria and hyper microalbuminuria. The intervention groups showed decreased microalbuminuria and there was no effect on blood glucose or body weight. Glomerular sclerosis and extracellular matrix (ECM) increased in model group and improved in irbesartan and XST groups as judged by HE, Masson and PAS stains. Three intervention groups had no effect on the elevated expression of MMP-2 in diabetic rats. Compared with the model group, the irbesartan, low-dosage and high-dosage XST groups had significantly decreased blood levels of NO ((104.9 ± 11.0) µmol/L vs (41.9 ± 9.6) µmol/L and (14.7 ± 1.9) µmol/L, P < 0.05) and MDA ((19.6 ± 1.6) nmol/L vs (6.6 ± 0.9) mol/L and (4.5 ± 1.2) nmol/L, P < 0.05), increased blood and urine activities of SOD (blood: (222 ± 20)×10(3) vs (231 ± 18)×10(3) and (237 ± 24)×10(3) U/L,P < 0.05), urine: (11.8 ± 1.1)×10(3) vs (23.3 ± 2.0)×10(3) and (25.7 ± 1.8)×10(3) U/L)., Conclusion: Compound Xueshuantong Capsule may decrease proteinuria through its suppression of oxidative stress and not its improvement of ECM metabolism.

Objective: To explore the adjunctive therapeutic effects of acupuncture for leukopenia induced by chemotherapy. METHODS Eighty six cases with leukopenia after chemotherapy treatment were randomly divided into a granulocyte colony-stimulating factor (G-CSF) plus acupuncture (A) group and a G-CSF group, 43 cases in each group. After chemotherapy treatments, the patients of both groups were treated with G-CSF for 4 times, with acupuncture at Zhigou (TE 6), Quchi (LI 11), Hegu (LI 4), etc. added in the G-CSF plus A group, for an observaion cycle of 45 days. Their therapeutic effects on the 10th and 31st day and peripheral white blood cell (WBC) counts and neutrophilic granulocyte classification on the 10th, 17th, 24th, 45th day after treatment were compared., Results: After they were treated on the 10th day, the effective rates were both 100.0% (both 43/43), and on the 31st day, the effective rate of 98.9% (42/43) in the G-CSF plus A group was higher than 91.1% (35/43) in the G-CSF group (P < 0.05). The WBC counts in the G-CSF plus acupuncture group were both higher than those in the G-CSF group on the 10th, 17th and 24th day after treatment (all P < 0.05). The ratios of mature neutrophilic granulocyte in the G-CSF plus A group were all higher than those in the G-CSF group at the same time (all P < 0.01)., Conclusion: Acupuncture can increase the therapeutic effect of G-CSF, delay the decrease of WBC after discontinuing G-CSF, promote the neutrophilic granulocyte differentiating forward to mature and it is better for improving leukopenia induced by chemotherapy.

Objectives: To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients., Methods: A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004. The fasting blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and concomitant disorders of the first screen during the hospitalization period were recorded. Those who had FBG level from 5.6 to 6.9 mmol/L and not been previously diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTT)., Results: Of the 8753 inpatients investigated, 1067 cases had complete medical records (CMR case) including PDM cases and previously non-diagnosed diabetes ones with FBG > or = 5.6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels from 5.6 to 6.9 mmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM, 21.7% was newly diagnosed diabetes mellitus (NDM), 29.1% had impaired glucose regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05, respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P < 0.05, respectively). Only 22.8% of the PDM inpatients underwent treatment of dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP-III. BMI was higher and waistline longer in the PDM and NDM inpatients than those in the NGT cases (P < 0.05, respectively). Seventy-two point eight percent of the PDM inpatients was complicated with more than one type of vascular diseases. Nine point seven percent and 0.2% of the NDM inpatients were tormented by diabetic nephropathy and diabetic retinopathy respectively., Conclusions: More inpatients with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which included hypertriglyceridemia, hypo-high-density lipoproteinemia and metabolic syndrome. Concomitant vascular diseases were more frequently found in PDM inpatients than in the others. Some of the NDM and IGT inpatients were complicated with microvascular diseases.

Objective: To investigate the haemodynamic and respiratory changes following intravenous administration with midazolam, pavulon or both of them in the patients having incoordination between spontaneous breathing and mechanical ventilation., Methods: Thirty patients having incoordination between spontaneous breathing and mechanical ventilation were randomly assigned to receiving intravenous injection of pavulon (group 1), midazolam (group 3), and both (group 2) respectively with 10 cases in each group. The degree of coordination between spontaneous breathing and mechanical ventilation, blood pressure (BP), heart rate (HR), respiration frequency (RF), oxygen saturation of pulse (SpO(2)) were observed before the medication and at 5, 15, 30 and 60 minutes following the administration of drugs in all the patients., Results: Incoordination between spontaneous breathing and mechanical ventilation, fast RF, decreased SpO(2) were observed before the drug in all patients. Improvement of respiratory was significant in group 2. Patients in group 2 were in excellent coordination between spontaneous breathing and mechanical ventilation, reaching 100% within 30 minutes after administration, and lasting longer. The haemodynamics maintained stable and a significant improvement in respiration and SpO(2) were found. BP and HR were elevated significantly, and RF and hypoxemia were improved, and the degree of coordination between spontaneous breathing and mechanical ventilation reached 100% 5 minutes after the drug, but with shorter duration in group 1. There were no obvious changes in BP, HR, RF and hypoxemia, and the degree of coordination between spontaneous breathing and mechanical ventilation was lowest in group 3., Conclusion: The combined use of midazolam and pavulon has little influence on circulation, and it also can maintain the coordination between spontaneous breathing and mechanical ventilation. It is suggested that the combined use of midazolam and pavulon is an optimal way to improve the ventilatory function in mechanical ventilation.