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Field research on phthalate monoesters (MPEs) and their relationships with phthalate esters (PAEs) is limited, especially in wild fishes. Here, PAEs and MPEs were measured in surface water, sediment, and wild fish collected from a representative river basin with high economic development. Several metabolites of emerging plasticizers, such as mono(3,5,5-trimethyl-1-hexyl) phthalate and mono(6-oxo-2-propylheptyl) phthalate, have already existed in fish with high detection frequencies (95 % and 100 %). Monobutyl phthalate and mono(2-ethylhexyl) phthalate were the predominant MPEs in fish and natural environment (surface water and sediment), while bis(2-ethylhexyl) phthalate was the most abundant PAEs in all matrices. The total concentrations (median) of 9 PAEs and 16 MPEs were 5980 and 266 ng/L in water, 231 and 10.6 ng/g (dw) in sediment, and 209 and 32.5 ng/g (ww) in fish, respectively. The occurrence of MPEs was highly related to their parent PAEs, with similar spatial distribution characteristics in the aquatic environments. Moreover, municipal wastewater discharge was recognized as the main source of MPEs in the research area. Fish species can accumulate targeted chemicals, and it seems more MPEs were from the PAE degradation in fish other than the direct uptake of MPEs in water. Parent PAEs showed higher ecological risk than their corresponding metabolites., 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 © 2024 Elsevier B.V. All rights reserved.)

Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR. Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis. Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups. Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909., 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 © 2024 Liu, Un, Bai, Chan, Zeng, Lei, Li and Ung.)

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole‑exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis‑like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG , STS , KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS : c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis‑associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.

Objective: To analyze the main disease composition of children hospitalized in pediatric surgery, explore the correlation between disease types and gender, and provide a reference for hospital management and pediatric disease prevention., Methods: Using ICD-10 codes as the classification standard for disease diagnosis, a statistical analysis was conducted on the disease composition of children hospitalized in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1, 2015, to December 31, 2015, followed by the establishment of a clinical database. A total of 1647 male patients and 817 female patients were enrolled in the study, resulting in a male-to-female ratio of 2:1. The age range of the patients spanned from 0 to 18 years, with a marked imbalance in patient distribution among the various age groups. Statistical analysis was conducted using SPSS version 18.0 software. A chi-square test was performed to analyze the differences in the composition of disease systems and the composition of major diseases in terms of sex and age., Results: Pediatric patients were admitted with complex and diverse diseases in 2015, involving 15 systems of the human body and 400 diseases. Digestive system diseases, tumors, congenital malformations, and genitourinary system diseases were the top four diseases accounting for 83.5% of all pediatric cases. 561 patients were aged 0 years, accounting for 22.3% of all cases, while 1,801 patients fell within the 0-5 years age group, constituting 73.1% of the total. The differences in disease system composition among different sex and age groups of pediatric surgical inpatients were statistically significant (P = .001). There are statistically significant differences in the length of hospital stay and hospitalization costs among pediatric surgical inpatients in different age groups (P = .001)., Conclusion: To strengthen the diagnosis and treatment of pediatric surgical diseases, we should strengthen the construction of key departments, optimize the consultation process according to the characteristics of children's disease spectrum, and improve the level of diagnosis and treatment of pediatric surgical diseases.

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective: To assess the feasibility, safety, and efficiency of simultaneous anterograde video laparoscopic inguinal and pelvic lymphadenectomy for penile cancer., Materials and Methods: We reviewed retrospectively the records of 22 patients (44 lateral) who underwent inguinal lymph nodes dissection for penile cancer. The procedure was standardized as two planes, three holes, and six steps. Two Separate-planes: superior plane of eternal oblique aponeurosis/ / fascia lata; inferior plane of superficial camper fascia. Three holes: two artificial lateral boundary holes, the internal and external boundary holes, and the hole of oval fossa. Six steps: separate the first separate-plane; separate the second layer; separate two artificial lateral boundary holes; free great saphenous vein; separate the third hole and clean up the deep inguinal lymph nodes; pelvic lymphadenectomy., Results: A total of 22 cases were included and 9 patients underwent simultaneous pelvic lymphadenectomy. The average operation time on both sides was 7.52 ± 3.29 h, which was 0.5-1 h/side after skilled. The average amount of bleeding was 93.18 ± 50.84 ml. A total of 8 patients had postoperative complications, accounting for 36.36%, and no complications great than Clavien-Dindo class III occurred., Conclusion: This study demonstrated that the video laparoscopic simultaneous anterograde inguinal and pelvic lymphadenectomy is a feasible and safe technique. Indocyanine Green was helpful for lymph node identify., 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., (© 2024 Yi, Li, Lu, Lu, Chen, Zeng, Qin, Wu and Tang.)

Liquid crystal monomers (LCMs) have been recognized as contaminants of emerging concerns. E-waste recycling sites and liquid crystal displays (LCDs) manufacturers are supposed to be critical sources. However, information regarding LCM contaminations in soils surrounding these sites are currently unavailable. In this study, soil samples were collected from two distinct areas in South China: e-waste recycling area (n = 36) and LCD manufacturer (n = 41), and 60 target LCMs (including 13 biphenyl and analogs (BAs), 10 cyanobiphenyl and analogs (CBAs), and 37 fluorinated biphenyl and analogs (FBAs)) were determined. The concentrations of LCMs in the soils from near the e-waste recycling area (0.32-18 ng/g, average: 4.2 ng/g) were higher than those surrounding the LCD manufacturer (ND - 7.2 ng/g, average: 1.5 ng/g). The compositional profiles of LCMs in soil samples from these two typical point sources were considerably different. The concentrations of FBAs exponentially decreased with distance from the e-waste recycling park, by >90 % within 2 km. The levels of BAs exhibited a similar exponential decrease with distance from the LCD manufacturer. The inventories of LCMs were estimated to be 21.0 kg in the e-waste recycling area and 10.8 kg in the LCD manufacturer area. Remarkably, the inventory of LCMs in soils from e-waste recycling area was one order of magnitude larger than that of hexabromocyclododecanes (HBCDs) in the same region, and 0.2 to 20 times the annual global emissions of LCMs from discarded LCD panels. More studies are required to elucidate the environmental occurrence, behavior, and fate of LCMs in multimedia environment surrounding typical point sources., 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 Elsevier B.V. All rights reserved.)

Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO 3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m 2 /g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC 50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC 50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 μg/mL, while the IC 50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 μg/mL and 40.05 ± 2.71 μg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications., 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 Elsevier B.V. All rights reserved.)

Background: One of the main causes of lung cancer-related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa&#95;circ&#95;0072309 may be employed as a potential biomarker for BM induced by non-small-cell lung cancer (NSCLC) and to understand its possible underlying mechanism., Methods: Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa&#95;circ&#95;001653, miR-100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and atypical chemokine receptor 3 (ACKR3) protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa&#95;circ&#95;0072309 and its relevant mechanism on BM development, an NSCLC-associated BM model in mice was established., Results: According to the results, miR-100 expression was down-regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ&#95;0072309 and ACKR3 expression were up-regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM- patients. Patients' serum exhibits the same level of hsa&#95;circ&#95;0072309/miR-100/ACKR3 expression as in BM samples. Advanced tumor-node-metastasis (TNM) stage, higher BM, shorter post-operative overall survival (OS), and progression-free survival (PFS) are all substantially associated with increased serum circ&#95;0072309 levels in BM+ patients. In animal models, serum owning hsa&#95;circ&#95;0072309 from BM+ patients facilitates BM formation by regulating the miR-100/ACKR3 pathway., Conclusions: The current preliminary research reveals serum hsa&#95;circ&#95;0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC-derived BM and suggests a substantial role for the hsa&#95;circ&#95;0072309/miR-100/ACKR3 axis in the formation of BM from NSCLC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Gravel (>2 mm) is one of the main parameters for estimating soil carbon pool. To assess the effects of gravel on soil bulk density (BD) and organic carbon density (SOCD) in Pinus massoniana plantations, we estimated the BD and SOCD at the 0-10, 10-20 and 20-40 cm soil depths of 131 plots under two different conditions, with and without removing gravel. The BD of each soil layer after removing gravel was 0.58-1.57, 0.60-1.67, and 0.59-1.75 g·cm -3 , respectively, which was significantly lower than that before removing gravel. Gravel increased the BD by 6.5%-6.8%. The SOCD of each soil layer before removing gravel was 8.93-65.97, 7.63-59.08, and 8.79-94.53 t·hm -2 , respectively, which was higher than that after removing gravel. Overall, by neglecting the effect of gravel, SOCD was overestimated by 4.9%-11.8%. As gravel content increased, the relative deviation in the estimated BD and SOCD among different methods increased. When the gravel content was higher than 20%, the estimated SOCD at soil layer of 0-40 cm showed a significant difference between neglecting gravel and removing gravel, with the former being 29.7%-47.4% higher than the latter. In conclusion, gravel markedly affected the estimations of BD and SOCD. It was recommended that SOCD should be estimated by the method that not only uses the BD after removing gravel but also considers gravel as a correction factor (especially when gravel content is above 20.0%) to avoid overestimation of soil carbon pool.

Take-out food has become increasingly prevalent due to the fast pace of people's life. However, few study has been done on microplastics in take-out food. Contacting with disposable plastic containers, take-out food may be contaminated with microplastics. In the present study, abundance and characteristics of microplastics in total of 146 take-out food samples including solid food samples and beverage samples (bubble tea and coffee) were determined and identified. The mean abundance of microplastics in take-out food was 639 items kg -1 , with the highest value in rice and the lowest value in coffee. Fragments shape, transparent color and sizes ≤ 500 μm were the main characteristics of microplastics in those food, and polyethylene was the main polymer type. Our results indicated that microplastics in take-out food was influenced by food categories and cooking methods, as well as food packaging materials. Approximately 170-638 items of microplastics may be consumed by people who order take-out food 1-2 times weekly., 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 Inc. All rights reserved.)

Research Question: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity?, Design: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo., Results: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%)., Conclusions: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

With the strict regulation of brominated flame retardants, organophosphate esters (OPEs) have been extensively used as replacements. Increasing concerns on OPEs have aroused due to their extensive distribution in the environment and humans, as well as their potential toxicities. Recent studies have demonstrated that some organophosphate di-esters are even more toxic than their respective tri-esters. This review summarized the current state of knowledge on the analytical methodologies (including sample collection and preparation, instrumental analysis, and the feasibility of each potential human matrix), as well as the occurrences of OPEs and/or their metabolites (m-OPEs) in various human matrices. Organophosphate esters are readily metabolized in human thus only limited studies reported their occurrences in blood and breast milk, whereas abundant studies are available regarding the occurrences of m-OPEs rather than OPEs in urine. Since none of the matrix is suitable all the time, appropriate matrix should be selected depending on the aims of biomonitoring studies, e.g., high throughput screening or body burden estimation. Biomonitoring with non-invasive matrices such as hair and/or nail is useful to screen specific populations that might be under high exposure risks while urine is more suitable to provide valuable information on body burden. In terms of urinary monitoring, specific biomarkers have been identified for some OPE compounds, including tri(2-butoxyethyl) phosphate, tri(1,3-dichloro-2-propyl) phosphate, tri(2-chloroethyl) phosphate and tri(1-chloro-2-propyl) phosphate. Further studies are required to identify suitable urinary biomarkers for other OPE compounds, especially the emerging ones., 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 present work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Inherited epidermolysis bullosa (IEB) represents a group of rare genetic dermatoses comprising various phenotypes ranging from severe cutaneous and extracutaneous involvement to mild cutaneous fragility. Pathogenic variants have been identified in at least 20 genes responsible for IEB. In the present study, six cases of epidermolysis bullosa were recruited and subjected to a combination of clinical and genetic analysis. The family history of each case was surveyed. Whole exome sequencing was performed to identify the causative variation. The six patients showed typical EB symptoms. In all cases, WES detected the diagnostic variations of the COL7A1 or DST gene. A total of 10 variants were identified and verified. The findings of the present study further expanded the mutation spectrum of IEB, provided evidence for genetic counseling to the affected families, as well as highlighted the complexity of the pathogenesis of IEB., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yao et al.)

We developed a digital optical phase locking loop (OPLL) with three advantages, including high precision of phase locking, high control bandwidth up to 2.8 MHz, and automatic laser locking strategy. Spaceborne laser interferometers will be used to measure tiny displacements caused by gravitational waves in millions of kilometers range. A slave laser will be heterodyne phase locked to the incoming weak light at the end of an arm, emitting a higher power light back to the other satellite to measure pathlength variations at the picometer level. Such accuracy requires extremely precise OPLL. We report an experiment to demonstrate a digital OPLL that can automatically lock two independent free-running Nd:YAG lasers with residual phase error below 1 m r a d / H z above 0.01 Hz, which is the best performance recorded for digital servos, to our knowledge. Such performance tested under a normal laboratory environment will be highly improved in a vacuum environment with temperature and vibration well controlled. Both the digital OPLL and the automatic strategy were implemented on a field programmable gate array that could be potentially used for future gravitational-wave detection. Our experiment might change the thinking of scientists who study phasemeters of gravitational-wave detection because we are aware that the digital phase locking loop used for "optical phase tracking" is differently designed from "optical phase locking."

Cardiac hypertrophy is a common cardiovascular disease that is found worldwide and is characterized by heart enlargement, eventually resulting in heart failure. Exploring the regulatory mechanism of cardiac hypertrophy is beneficial for understanding its pathogenesis and treatment. In our study, we have showed TINCR was downregulated and miR-211-3p was upregulated in TAC- or Ang II-induced models of cardiac hypertrophy. Dual luciferase and RIP assays revealed that TINCR served as a competitive endogenous RNA (ceRNA) for miR-211-3p. Then, we observed that knockdown of miR-211-3p alleviated TAC- or Ang II-induced cardiac hypertrophy both in vivo and in vitro. Mechanistically, we demonstrated that miR-211-3p directly targeted VEGFB and thus regulated the expression of SDF-1α and CXCR4. Rescue assays further confirmed that TINCR suppressed the progression of cardiac hypertrophy by competitively binding to miR-211-3p, thereby enhancing the expression of VEGFB and activating the VEGFB-SDF-1α- CXCR4 signal. Furthermore, overexpression of TINCR suppressed TAC-induced cardiac hypertrophy in vivo by targeting miR-211-3p-VEGFB-SDF-1α- CXCR4 signalling. In conclusion, our research suggests that LncRNA TINCR improves cardiac hypertrophy by targeting miR-211-3p, thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis. TINCR and miR-211-3p might act as therapeutic targets for the treatment of cardiac hypertrophy., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

This study explored the effects of renal sympathetic denervation (RDN) on hyperlipidity-induced cardiac hypertrophy in beagle dogs. Sixty beagles were randomly assigned to the control group, RDN group, or sham-operated group. The control group was fed with a basal diet, while the other two groups were given a high-fat diet to induce model hypertension. The RDN group underwent an RDN procedure, and the sham-operated group underwent only renal arteriography. At 1, 3, and 6 months after the RDN procedure, the diastolic blood pressure (DBP) and systolic blood pressure (SBP) levels were markedly decreased in the RDN group relative to the sham group ( P < 0.05). After 6 months, serum norepinephrine (NE) and angiotensin II (AngII), as well as left ventricular levels, in the RDN group were statistically lower than those in the sham group ( P < 0.05). Also, the left ventricular mass (LVM) and left ventricular mass index (LVMI) were significantly decreased, while the E/A peak ratio was drastically elevated ( P < 0.05). Pathological examination showed that the degree of left ventricular hypertrophy and fibrosis in the RDN group was statistically decreased relative to those of the sham group and that the collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) were also significantly reduced ( P < 0.05). Renal sympathetic denervation not only effectively reduced blood pressure levels in hypertensive dogs but also reduced left ventricular hypertrophy and myocardial fibrosis and improved left ventricular diastolic function. The underlying mechanisms may involve a reduction of NE and AngII levels in the circulation and myocardial tissues, which would lead to the delayed occurrence of left ventricular remodeling., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Shan Tu et al.)

Fas binding factor 1 (Fbf1) is one of the distal appendage proteins in the centriole, located at its distal and proximal ends. It influences the duplication and separation of centrosomes, thereby affecting the progression of the cell cycle during mitosis. However, the function of Fbf1 in meiosis has remained unclear. To explore the role of Fbf1 in the in vitro maturation of mouse oocyte, immunofluorescence staining was used to examine the Fbf1 location in the oocyte and their phenotype after protein deletion. Western blot was used to examine the protein abundance. This study showed that mouse oocytes express Fbf1 which locates at the spindle poles and around the microtubules. Through taxol and nocodazole treatment, and microinjection of siRNA, it was demonstrated that Fbf1 had an important role in the spindle assembly and chromosome separation during mouse oocyte meiosis In particular, microinjection of Fbf1-siRNA resulted in severe abnormalities in the spindle and chromosome arrangement, decreased aggregation of microtubules, disrupted the first oocyte meiosis, and the extrusion of the first polar body. Furthermore, in the Fbf1-siRNA group, there was reduced expression of Plk1 and its agglutination at the spindle poles, along with retarded chromosome segregation due to the activation of the spindle assembly checkpoint (SAC) component BubR1. These results indicate that Fbf1 may function in microtubule depolymerization and agglutination, control the microtubule dynamics, spindle assembly and chromosome arrangement and, thus, influence the mouse oocyte meiotic maturation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The relationship between parity and atherosclerosis has been reported in some ethnic populations. However, results regarding Chinese women are still lacking. This study aimed to investigate the association of parity and carotid atherosclerosis, which has a predictive value of subsequent atherosclerotic events in elderly Chinese women., Methods: A total of 2, 052 participants from the medical examination center of the Third Xiangya Hospital were enrolled in the study. A standardized, structured questionnaire was administered to collect information on subjects' demographic characteristics, socioeconomic status, and cardiovascular risk factors. High-resolution ultrasound was used to examine carotid plaques and carotid intima-media thickness (IMT)., Results: The mean age of participants was 66.1 ± 5.5 years. Women with more birth appeared to have a higher risk of carotid artery plaques. A multivariate-adjusted model yielded an odds ratio of 1.38 (95% CI: 12%-70%, P = 0.003) per birth. A positive association was observed between parity and common carotid IMT (β ± SE: 0.029 ± 0.006, P < 0.001), and internal carotid IMT (β ± SE: 0.011 ± 0.005, P = 0.03) in a univariate model; however, these associations became non-significant in multivariate-adjusted models. When common carotid IMT was classified into an IMT ≥ 1 mm group and an IMT < 1 mm group, higher parity was associated with more obvious thickening both in the unadjusted model (OR = 1.61, 95% CI: 1.29-2.00, P < 0.001) and in the fully adjusted model (OR = 1.43, 95% CI: 1.09-1.88, P = 0.01)., Conclusions: There is a positive association between parity and risk of carotid plaques, as well as between parity and risk of obvious thickening for common carotid IMT in elderly Chinese women, indicating multiparous women might experience more atherosclerotic challenges., (Copyright and License information: Journal of Geriatric Cardiology 2020.)

Background: The incidence of insulin resistance (IR) has rapidly increased worldwide over the last 20 years, no perfect solution has yet been identified. Finding new therapeutic drugs will help improve this situation. As a traditional Chinese medicine, PPM (processed Polygonum multiflorum) has widely been used in the clinic. Recently, other clinical functions of PPM have been widely analyzed., Results: Administration of the water extract from PPM decreased the level of FBG, TC, and TG, and increased the level of FGC, thereby reducing the IR index and improving IR. Furthermore, Western blot analysis revealed that PPM significantly increased GPR43 and AMPK expression when compared with the MOD group, and GPR43, AMPK were known as glucose metabolism-related proteins. In addition, treatment with PPM can restore the balance of gut microbiota by adjusting the relative abundance of bacteria both at the phylum and genus level, and these changes have been reported to be related to IR., Methods: Sprague Dawley (SD) rats were fed a high-fat diet and were gavaged daily with either normal saline solution or PPM for 12 weeks. Major biochemical indexes, such as fasting blood glucose (FBG), fasting glucagon (FGC), total cholesterol (TC), and triglyceride (TG) were measured. Then the protein expression of adenosine 5'-monophosphate -activated protein kinase (AMPK) and G protein-coupled receptor 43 (GPR43) was evaluated by using Western blot analysis. Moreover, the composition of gut microbiota was assessed by analyzing 16S rRNA sequences., Conclusions: Our findings showed that PPM reversed the increasing of FBG and the decreasing of IRI, PPM accelerated the expression of glucose metabolism-related proteins and regulated the intestinal microecological balance. Therefore, we hold the opinion that PPM may be an effective option for treating IR.

In recent years, the incidence of diseases associated with hepatic injury has increased in prevalence. Targeting the mitochondria to protect liver function has gained momentum due to their central role in energy production, apoptotic cell death, oxidative stress, calcium homeostasis, and lipid metabolism. In this study, we employed a hepatic mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method (CM-HMC) to identify hepatic mitochondria ligands from medicinal herbs (MHs) including Notopterygii Rhizoma et Radix (NRR) that possess hepatic-protective effects. A total of 4 newly identified mitochondrial ligands were successfully identified by CM-HMC. The mitochondria-regulating activities of 3 of the 4 hits were confirmed using isolated mitochondria. The hepatic-protective effects of one of these hits were validated in carbon tetrachloride-damaged human liver L02 cell models. We have thus identified new natural hepatic-protectants that enhance our understanding of the hepatic-protective mechanisms of MHs. CM-HMC was proven to efficiently screen for mitochondrial ligands from MHs., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2019 Li Liang et al.)

Background: Mitochondrial dysfunction is an important mechanism of non-alcoholic fatty liver disease (NAFLD). Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for NAFLD therapy. In China, Polygonatum kingianum (PK) has been used as a herb and food nutrient for centuries. So far, studies in which the effects of PK on NAFLD are evaluated are lacking. Our study aims at identifying the effects and mechanism of action of PK on NAFLD based on mitochondrial regulation., Methods: A NAFLD rat model was induced by a high-fat diet (HFD) and rats were intragastrically given PK (1, 2 and 4 g/kg) for 14 weeks. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in oxidative stress, energy metabolism, fatty acid metabolism, and apoptosis were investigated., Results: PK significantly inhibited the HFD-induced increase of alanine transaminase, aspartate transaminase, total cholesterol (TC), and low density lipoprotein cholesterol in serum, and TC and triglyceride in the liver. In addition, PK reduced high density lipoprotein cholesterol and liver enlargement without affecting food intake. PK also remarkably inhibited the HFD-induced increase of malondialdehyde and the reduction of superoxide dismutase, glutathione peroxidase, ATP synthase, and complex I and II, in mitochondria. Moreover, mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2 was significantly up-regulated and down-regulated after PK treatment, respectively. Finally, PK notably inhibited the HFD-induced increase of caspase 9, caspase 3 and Bax expression in hepatocytes, and the decrease of expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria., Conclusion: PK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD., (Copyright © 2019. Published by Elsevier Masson SAS.)

Targeting mitochondria as a hepatic-protective strategy has gained attention, because of their important roles in energy production, adjustment of apoptosis, and generation of reactive oxygen species. To promote the discovery of natural mitochondria-targeted hepatic-protectants, we established a hepatocellular mitochondria-based capturing method by coupling affinity ultrafiltration with liquid chromatography/mass spectrometry (LC/MS), which is suitable for identifying mitochondrial ligands from medicinal herbs (MHs). After evaluating the feasibility of the method, it was applied for capturing mitochondria-targeting constituents from Peucedani Radix extract. A total of 10 active compounds were identified by LC/MS, all of which were newly identified mitochondrial ligands. The mitochondria-remedying activity of 4 of the 10 hits was confirmed by pharmacological tests in vitro . Additionally, the hepatic-protective abilities of 4 hits were verified in both carbon tetrachloride-damaged liver L02 cells and mice. These results indicated that the method could be used for identifying hepatic mitochondria-targeting constituents in MHs, which might be beneficial for hepatic-protective development.

Aim: To identify the effects and mechanism of action of Polygonatum kingianum ( P. kingianum ) on dyslipidemia in rats using an integrated untargeted metabolomic method., Methods: A rat model of dyslipidemia was induced with a high-fat diet (HFD) and rats were given P. kingianum [4 g/(kg•d)] intragastrically for 14 wk. Changes in serum and hepatic lipid parameters were evaluated. Metabolites in serum, urine and liver samples were profiled using ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify potential biomarkers and metabolic pathways., Results: P. kingianum significantly inhibited the HFD-induced increase in total cholesterol and triglyceride in the liver and serum. P. kingianum also significantly regulated metabolites in the analyzed samples toward normal status. Nineteen, twenty-four and thirty-eight potential biomarkers were identified in serum, urine and liver samples, respectively. These biomarkers involved biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine and isoleucine, along with metabolism of tryptophan, tyrosine, phenylalanine, starch, sucrose, glycerophospholipid, arachidonic acid, linoleic acid, nicotinate, nicotinamide and sphingolipid., Conclusion: P. kingianum alleviates HFD-induced dyslipidemia by regulating many endogenous metabolites in serum, urine and liver samples. Collectively, our findings suggest that P. kingianum may be a promising lipid regulator to treat dyslipidemia and associated diseases., Competing Interests: Conflict-of-interest statement: The authors declare that there is no duality of interest associated with this manuscript.

Carbon spheres and tubes were formed from acetylene decomposition on SBA-15 and Ni-SBA-15 at 650-850 °C. At 650 °C, the decomposed carbons covered the surface of the support, and no carbon spheres and filament materials were formed. Carbon sphere formation occurred at 750 °C-850 °C; with diameters ranging from 0.8 μm-1.1 μm. For Ni-SBA-15, the diameters of the spheres and filaments were 0.8 μm and 62 nm, respectively, at 650 °C. At 750 °C, the diameter of the ball carbon materials ranged from 0.7 μm-0.8 μm, the diameter of the carbon tubes formed was 120-130 nm, and their pore diameter was 8.0 nm-11 nm. At 850 °C, the diameters of ball carbon materials and carbon tubes were similar to those of the materials at the formation temperature, 750 °C. Si, O and C were the main constituents of SBA-15; Ni-SBA-15 and carbon material formation supports. High-ring PAHs (such as BaP (five rings); IND (six rings); DBA (five rings) and B[ ghi ]P (six rings)) exist in carbon materials. SBA-15 revealed insignificant cytotoxicity, but Ni-SBA-15 inhibited the proliferation of human lung cancer cells (A549). Less inhibition on cell viability and reactive oxidative species (ROS) generation on A549 were determined for carbon material formation on the Ni-SBA-15 compared to the Ni-SBA-15.

β-Arrestins (β-arrs) are regulators and mediators of G protein-coupled receptor signaling, and accumulating evidence suggests that they are functionally involved in inflammation and autoimmune diseases. However, the effect of β-arrs is unclear in inflammatory bowel disease (IBD), and the role of β-arr2 is unknown in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study is to investigate whether β-arr2 encourages inflammation-induced epithelial apoptosis through endoplasmic reticulum (ER) stress/p53-upregulated modulator of apoptosis (PUMA) in colitis. In the present study, the results showed that β-arr2 was increased in specimens from patients with UC or CD. Furthermore, a β-arr2 deficiency significantly repressed intestinal inflammation, ameliorated colitis, and alleviated mucosal apoptosis in mice. In addition, the targeted deletion of β-arr2 depressed ER stress, inhibited PUMA, and downregulated PUMA-mediated mitochondrial apoptotic signaling in colitis. β-Arr2, an important modulator of G protein-coupled receptor function, binds eIF2α to activate ER stress signaling. Furthermore, the knockdown of PUMA dramatically prevented β-arr2-induced apoptosis via alleviating ER stress in vitro. The results suggest that β-arr2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis and that β-arr2 is a potential therapeutic target for colitis.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. Different studies have shown decreased bone mineral density (BMD) in patients with SLE. The objective of this study was to investigate the prevalence and possible risk factors of low BMD in untreated female patients with SLE in Chinese population. A total of 119 untreated female patients with SLE were included. BMD was measured at lumbar spine and at total hip by dual-energy X-ray absorptiometry. The associations between decreased BMD and demographic variables, clinical variables, and bone metabolism variables were analyzed. These SLE patients had the following characteristics: mean age was 32.6 ± 11.9 years, mean disease duration was 22.1 ± 34.5 months, and mean SLEDAI was 11.4 ± 5.4. Osteopenia was present in 31.1% of the patients and osteoporosis in 8.5%. A significant negative association between low density lipoprotein cholesterol (LDL-c) and BMD at the lumbar spine (correlation coefficient = -0.242; P = 0.023) and total hip (correlation coefficient = -0.259; P = 0.019) was shown. These results seem to indicate that increased LDL-c may be an important risk factor for low BMD at lumbar spine and total hip in untreated female SLE patients.

There are no clinical studies on the effects of catheter-based radiofrequency renal denervation (RDN) on renal artery structure using 64-detector computed tomography (CT). A total of 39 patients with resistant hypertension received RDN and 38 patients received drug treatment. Mean systolic pressure and diastolic pressure in the RDN group decreased after 1, 3, 6, and 12 months of procedure (P<.05) and urinary protein level significantly decreased after 6 and 12 months (P<.05). The diameter, length, and sectional area of the renal artery; number of cases of atherosclerosis; and plaque burden of 64-detector CT renal arteriography did not change at 12 months of follow-up (P<.05), whereas the plaque burden increased significantly in the control group (P<.05). RDN significantly and persistently reduced blood pressure and decreased urinary protein excretion rate in patients with resistant hypertension and did not exhibit any adverse effect on renal function and renal artery structure., (© 2014 The Authors Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.)

Carbon materials including carbon spheres and nanotubes were formed from acetylene decomposition on hydrogen-reduced SBA-15 and Ni-SBA-15 at 650-850°C. The physicochemical characteristics of SBA-15, Ni-SBA-15 and carbon materials were analyzed by field emission scanning electronic microscopy (FE-SEM), Raman spectrometry, and energy dispersive spectrometry (EDS). In addition, the contents of polyaromatic hydrocarbons (PAHs) in the tar and residue and volatile organic compounds (VOCs) in the exhaust were determined during acetylene decomposition on SBA-15 and Ni-SBA-15. Spherical carbon materials were observed on SBA-15 during acetylene decomposition at 750 and 850°C. Carbon filaments and ball spheres were formed on Ni-SBA-15 at 650-850°C. Raman spectroscopy revealed peaks at 1290 (D-band, disorder mode, amorphous carbon) and 1590 (G-band, graphite sp(2) structure)cm(-1). Naphthalene (2 rings), pyrene (4 rings), phenanthrene (3 rings), and fluoranthene (4 rings) were major PAHs in tar and residues. Exhaust constituents of hydrocarbon (as propane), H2, and C2H2 were 3.9-2.6/2.7-1.5, 1.4-2.8/2.6-4.3, 4.2-2.4/3.2-1.7% when acetylene was decomposed on SBA-15/Ni-SBA-15, respectively, corresponding to temperatures ranging from 650 to 850°C. The concentrations of 52 VOCs ranged from 9359 to 5658 and 2488 to 1104ppm for SBA-15 and Ni-SBA-15 respectively, at acetylene decomposition temperatures from 650 to 850°C, and the aromatics contributed more than 87% fraction of VOC concentrations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Unlabelled: To investigate the expression of Ataxin-3 in human gastric cancer tissues and cell lines, and explore its clinical pathologic significance., Methods: The expression of Ataxin-3 in gastric cancer (n=536) and noncancerous gastric mucosa (n=312) was determined by immunohistochemistry and correlated to clinicopathologic features such as histologic differentiation and tumor size. The expression of Ataxin-3 protein in the human gastric cancer cell lines MKN45, SGC7901 and in normal human gastric epithelial cells (GES-1) was also evaluated by Western blot analysis. Quantitative real-time PCR was used to determine Ataxin-3 mRNA expression in human gastric cancer cell lines and tissues., Results: The expression of Ataxin-3 protein was decreased in the gastric cancer compared to noncancerous gastric tissue, and correlated with tumor size, Lauren classification, histologic differentiation, and mutant p53 protein (P < 0.05). Similarly, Ataxin-3 mRNA expression was decreased in the gastric cancers compared to the noncancerous gastric tissue. Ataxin-3 protein and mRNA expression was lower in MKN45, SGC7901 cells than in the normal GES-1 cells., Conclusion: Decreased expression of Ataxin-3 may play an important role in gastric carcinogenesis and development of gastric cancer.

Significant correlations between concentrations of PBDEs and heavy metals were observed in the human body. However, there is a lack of evidence on the linkage between the uptake of heavy metals and PBDEs. This study is the first report on the BDE-47 uptake profile in a human cell line. Hg and As exposures to KERTr (human skin derived keratinocyte) did not significantly (p > 0.05) affect the uptake of BDE47, whereas Pb and Cd significantly (p < 0.05) affected the uptake of BDE-47 in KERTr. The change in Km was minor after exposure to all heavy metals. The maximum transport rate (Vmax) after exposure to Pb (Vmax: 5.23 ± 0.49) and As (Vmax: 4.95 ± 0.60) was significantly increased when compared with the background of the KERTr cell line (Vmax: 4.07 ± 0.35). Real-time RT-PCR indicated that OATP-B, OATP-D, and OATP-E were expressed in the KERTr cell line. The upregulation or downregulation of OATP B and D genes were minor after exposure to heavy metals, but the OATP E gene was upregulated by three to fourfold in KERTr cell line after exposure to Pb an Cd, which may explain the significant increase of uptake of BDE-47 in KERTr after exposures to Pb and Cd. This study indicated that the uptake effects should be considered when performing risk assessment of human exposure to PBDEs and heavy metal., (Copyright © 2013 Wiley Periodicals, Inc.)

Aim: To investigate whether expression of cancer stem cell (CSC) markers is associated with recurrence and survival in hepatocellular carcinoma (HCC) patients., Methods: A consecutive series of 90 HCC patients who underwent curative hepatectomy between April 2007 and April 2009 were analyzed. Of the 90 patients, 38 (42%) experienced recurrence within two years of surgery. To adjust for baseline differences between this early recurrence group and the other patients, propensity-score matching was used to generate 25 pairs of patients. Immunohistochemistry was used to compare expression of CD133, CD90, and epithelial cell adhesion molecule (EpCAM) in liver tissues from propensity score-matched patients and from 10 healthy adults. Associations of the three markers with HCC, clinicopathological characteristics, early recurrence, and survival time were explored., Results: The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue (P < 0.001 for all). Among the HCC clinicopathology characteristics examined, the absence of tumor capsule was associated with CD133 expression (P = 0.005); higher histopathology grade and larger tumor size were associated with CD90 expression (P = 0.010 and 0.034, respectively); and elevated serum alpha-fetoprotein levels were associated with EpCAM expression (P = 0.021). Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients (P = 0.001 and 0.045, respectively), whereas CD133 expression was not significantly different between the two groups (P = 0.440). Multivariate analysis identified only CD90 expression as significantly associated with early recurrence. Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients. Cox regression identified EpCAM expression as an independent predictor of survival time., Conclusion: Expression of CD133, CD90, and EpCAM CSC markers may be linked to HCC tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.

Background & Aims: microRNA-122 is the only identified liver-specific miRNA and plays a crucial role in liver development, maintenance of hepatic homeostasis as well as tumourigenesis. In our previous differentiation of ESCs into hepatocytes, microRNA-122 (miR-122) was expressed at a relatively low level. Here, we aim to elucidate the effect and underlying mechanisms of miR-122 during differentiation of ESCs into hepatocytes., Methods: Mouse ESCs were initially induced towards HPCs by activin A, FGF-4 and sodium butyrate and were subsequently transfected with a recombinant adenovirus expressing vector pAV.Ex1d-CMV>miR-122/IRES/eGFP 9 days after induction. Cells were analysed by real-time PCR, immunofluorescence, flow cytometry, microscopy and functional assays. Furthermore, microarray analysis was performed., Results: We demonstrated that overexpression of miR-122 could effectively promote hepatic differentiation and maturation, as assessed by morphological and functional tests. The microarray analysis revealed that 323 genes were down-regulated, whereas 59 were up-regulated. Particularly, two liver-specific transcription factors, FoxA1 and HNF4a, were significantly up-regulated. Moreover, the expression of E-cadherin was dramatically increased and the proliferation of HPCs was suppressed, whereas knockdown of FoxA1 reduced E-cadherin expression and increased the proliferation of HPCs. In addition, the expression levels of FoxA1, HNF4a and E-cadherin in time-course transfection experiments with miR-122 were not significantly increased except in cells in which transfection with miR-122 occurred 9 days after induction., Conclusion: Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Differential expression of rice oxalate oxidase genes (OsOxO1-4) in rice leaves (Oryza sativa L.) in response to biotic stress was assayed using RT-PCR. OsOxO4 was induced transiently at 12 h in plants inoculated with the pathogens of bacterial blight and that of the wounding control. Inoculation with the rice blast pathogen induced OsOxO2 expression compared to the mock spray control. Overexpressing OsOxO1 or OsOxO4 in rice resulted in elevated transcript levels of the respective transgene as well as OsOxO3 in leaves compared to that in untransformed wild type (WT). In a line of RNA-i transgenic rice plants (i-12), expression of all four OsOxO genes except that of OsOxO2 was severely inhibited. Oxalate oxidase (OxO, EC 1.2.3.4) activity in plants overexpressing OsOxO1 or OsOxO4 was substantially higher than that in WT and the RNA-i lines. It was found that transgenic rice plants with substantially higher OxO activity were not more resistant to rice blast and bacterial blight than WT. In contrast, some RNA-i lines with less OxO activity seemed to be more resistant to rice blast while some overexpressing lines were more susceptible to rice blast than WT. Therefore, OxO might not be a disease resistance factor in rice.

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and may play an important role in carcinogenesis. We investigated the role of genetic polymorphisms at XRCC4 codon 247 (rs3734091, XRCC4P) and XRCC5 codon 180 (rs80309960, XRCC5P) in liver cancer (hepatocellular carcinoma) caused by aflatoxin B1 (AFB1)., Methods: A hospital-based case-control study, including 1499 liver cancer cases and 2045 controls without any liver disease, was conducted in a high aflatoxin exposure area in the Guangxi region of China to assess the relationship between these two polymorphisms and aflatoxin-related liver cancer risk and prognosis. Genotypes, mRNA levels, and the hot-spot mutation of TP53 gene (TP53M) related to AFB1 exposure was tested using TaqMan-PCR technique. XRCC4 protein level was analyzed by immunohistochemistry., Results: For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased liver cancer risk (odds ratio [OR] = 1.35 and 2.02, respectively). Significant interactive effects between risk genotypes (OR > 1) and aflatoxin exposure status were also observed in the joint effects analysis. Moreover, this polymorphism was associated not only with lower XRCC4 expression levels but also with higher AFB1-DNA adduct levels and increasing TP53M and portal vein tumor risk. Additionally, XRCC4P modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure., Conclusion: XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure.

Objective: Analysis of the pathogenesis of cytomegalovirus (CMV) infection for rat chronic liver rejection., Methods: Based on animal models that we previously developed, we divided control and a CMV infection group to analyze survival, histopathology and rejection activity. The level and mRNA expression of transforming growth factor-β1, platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) were measured in peripheral blood serum and liver tissue., Results: Obliterative arteriopathy and fibrosis was significantly greater in the CMV infection versus the control group (P < .05). PDGF mRNA expression in rat liver and in peripheral blood were significantly higher in the CMV infection versus the control group (P < .05). bFGF mRNA expression in the CMV infection group was also significantly higher than among the controls (P < .05)., Conclusions: CMV infection aggravated foam cell obliterative arteriopathy and liver fibrosis in chronic liver rejection, processes that accelerate the immune response, which may correlate with early high PDGF and bFGF expression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: With the optimal acceptance of its clinical advantages, laparoscopic splenectomy (LS) emerged as a gold standard procedure as compared with open splenectomy (OS). However, it is still controversial and even counted as contraindication for massive splenomegaly. Here, we aim to summarize the experiences, characteristics and trends of modified LS for massive splenomegaly in children with hematological disorders., Methods: Retrospective series of 57 pediatric patients with massive splenomegaly who underwent splenectomy from March 2007 to December 2011 were designated for this clinical analysis. The main outcome measures were dealt by statistics. For 30 cases of LS, we strictly adhered to the principle of using only three trocars to operate and initial ligation of the splenic artery, followed by retrieving the piecemeal of spleen through an accessory incision of 2-3 cm at 12 mm trocar port site., Results: Of the 57 pediatric patients, 27 underwent OS and 30 underwent LS, respectively. Despite the operative time being shorter for OS than for LS (P < 0.001), the blood loss was lower in LS than in OS (P < 0.001); the time required for oral intake as well as duration of hospital stay was lower in LS than in OS (P < 0.001). Post-operatively, 7 (25.9 %) complications occurred in OS and 3 (10 %) in LS. The conversion rate of LS to OS was 13.33 % in four cases till 2009., Conclusions: Despite the conflicting reports regarding the safety of LS for massive splenomegaly, we demonstrated that our modified laparoscopic splenectomy in the treatment of children with massive splenomegaly in hematological diseases seemed to achieve the fundamental goal of less invasion; it was safe and feasible.

Unlabelled: BACKGROUD/AIM: Because of the oncogenic risk, it is important to gain the homogeneous and purified cells from differentiated ESCs before transplantation. Here, we aim to select hepatocyte-like cells from differentiated ESCs, and investigate their growth, differentiation and neoplastic formation after intrahepatic transplantation., Methods: Mouse ESCs were primarily induced by Dexamethesone, FGF-4 and HGF sequentially, then placed to a conditioning selection media consisting of 5% cholestatic sera and cultivated for 2 wks. After labeled by CFDA-SE, the selected cells were transplanted into mouse liver in therapeutic liver repopulation models., Results: In the early stage of screening cultivation, most cells were suffered from apoptosis or even death. 1w later, some hepatocyte-like colony-forming units were observed, then the selected cells could grow and tend to be more mature, as assessed by morphological and functional tests. After intrahepatic transplantation, the labeled cells could proliferate and expressed albumin. Moreover, teratoma didn't form over 3 months., Conclusion: Our conditioning selection media could not only effectively select hepatocyte-like cells from differentiated ESCs, but further promote their growth and differentiation as well. After intrahepatic transplantation in therapeutic liver repopulation models, the selected cells could grow, differentiate and keep partial hepatic function. In particular, the transplantation was safe., (Copyright © 2012 S. Karger AG, Basel.)

Background: A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens., Findings: Oxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes., Conclusions: By compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.