Activation of N-Methyl-D-aspartate receptor contributed to the ultrasonic modulation of neurons in vitro.

Ultrasound stimulation is increasingly used to investigate brain function and treat brain diseases due to its high level of safety and precise spatiotemporal resolution. Therefore, it is crucial to understand the underlying mechanisms involved in ultrasound brain stimulation. In this study, we investigate the role of NMDA receptors in mediating the effects of ultrasound on primary hippocampal neurons in mice. Our results show that ultrasound alone can activate heterologous NMDA receptor subunits, including NR1A, NR2A, and NR2B, in 293T cells, as well as endogenous NMDA receptors in primary neurons. This activation leads to an influx of calcium and an increase in nuclear c-Fos expression in primary neurons that have not been pre-treated with an NMDA receptor inhibitor. In conclusion, our findings demonstrate that NMDA receptors contribute to neuronal activation by ultrasound stimulation in vitro, providing insight into the molecular mechanisms of ultrasound neuromodulation and a new mediator for the sonogenetics technique.

L007-0069 kills Staphylococcus aureus in high resistant phenotypes.

Staphylococcus aureus, a common gram-positive pathogenic bacterium, is a main cause of hospital infection. The prevalence rate of methicillin-resistant S. aureus (MRSA) has made its treatment difficult in recent decades. Moreover, S. aureus in the highly tolerant format of biofilm or persister often renders infections refractory. Thus, developing new active compounds against resistant S. aureus is urgently needed. In this study, by a high-throughput screening assay, we identified a small molecule, L007-0069, that exhibited strong and effective bactericidal activity against S. aureus and its high resistance patterns, such as biofilms and persisters, with a low probability of inducing resistance. By molecular dynamics and fluorescent probe analysis, mechanistic studies revealed that the bactericidal activity of L007-0069 was mainly mediated by membrane disruption and metabolic disorder induction. Furthermore, L007-0069 showed effective anti-MRSA effects in vivo in both a wound infection model and a peritonitis-sepsis model, with no detectable toxicity observed at the therapeutic dosage. In conclusion, L007-0069 has the potential to become an alternative for the treatment of highly resistant S. aureus-related infections.

Complete mitogenome of Treron sphenurus (Aves, Columbiformes): the first representative from the genus Treron, genomic comparisons and phylogenetic analysis of Columbidae.

The wedge-tailed green pigeon (Treron sphenurus) has a protective value in the evolution of the family Columbidae. In this study, the complete mitogenome of T. sphenurus from Baise City, China, which represents the first sequenced species of the genus Treron in Tribe Treronini, is reported. This was accomplished using PCR-based methods and a primer-walking sequencing strategy with genus-specific primers. The mitogenome was found to be 18,919 bp in length comprising 37 genes, including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one control region. In terms of structure and composition, many similarities were found between the T. sphenurus and Hemiphaga novaeseelandiae (New Zealand pigeon) mitogenomes. This was further supported by phylogenetic analysis showing that T. sphenurus has a close evolutionary relationship with H. novaeseelandiae. The complete mitogenome of T. sphenurus reported here is expected to provide valuable molecular information for further studies on the phylogeny of the genus Treron and for analyses of the taxonomic status of the family Columbidae.

A natural reassortant and mutant serotype 3 reovirus from mink in China.

Mammalian orthoreoviruses (MRVs) are widespread and infect virtually all mammals. We report here the first case of a natural mutant and reassortant serotype 3 reovirus from mink in China, known as MRV3 SD-14. Whole-genome sequence analysis showed that the MRV3 SD-14 may have resulted from a reassortment involving MRVs that infected swine, humans and mink. Interestingly, the S1 segment, which encodes the viral attachment protein σ1, which influences viral virulence and cell tropism in the host, had a stop codon mutation at amino acid 246. Surveillance of the virulence and evolution of MRVs in humans and other animals deserves more attention.

Clinical classification of Caroli's disease: an analysis of 30 patients.

BACKGROUND: Caroli's disease (CD) is a rare congenital disorder. The early diagnosis of the disease and differentiation of types I and II are of extreme importance to patient survival. This study was designed to review and discuss observations in 30 patients with CD and to clarify the clinical characteristics of the disease. METHODS: The demographic and clinical features, laboratory indicators, imaging findings and pathology results for 30 patients with CD were reviewed retrospectively. RESULTS: Caroli's disease can occur at any age. The average age of onset in the study cohort was 24 years. Patients who presented with symptoms before the age of 40 years were more likely to develop type II CD. Approximately one-third of patients presented without positive signs at original diagnosis and most of these patients were found to have type I CD on pathology. Anaemia, leucopoenia and thrombocytopoenia were more frequent in patients with type II than type I CD. Magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) examinations were most useful in diagnosing CD. CONCLUSIONS: No typical symptoms, signs or laboratory indicators are able to distinguish CD from other conditions. Both MRCP and CT were most valuable in diagnosis. The two types of CD may be differentiated by age of onset and routine blood tests.

[Clinical application of virtual surgery combined with guide plate in reduction and fixation of condylar neck fracture in 7 patients].

PURPOSE: To explore the value of virtual surgery and 3D printing model combined with guide plate in treatment of mandibular condylar neck fracture. METHODS: Seven patients with mandibular condylar neck fracture were scanned by CT for original data. The data were exported in DICOM format. A three-dimensional model was reconstructed using software, the fracture was reduced by virtual surgery, and the 3D model was printed by a 3D printer. A prebent titanium plate was used to fabricate the guide plate, which was used for reduction and fixation of the fracture block during surgery. RESULTS: All the postoperative incisions revealed no signs of infection, the wounds were hidden and beautiful. The implanted titanium plates were highly compatible with the reduced fracture segments. The patients were followed up for 6 months after surgery, the condylar fracture healed well and there was no obvious displacement. The patient developed no mandibular deviation with a stable occlusion, and no occlusal pain was reported. No obvious temporomandibular joint disorder was present. CONCLUSIONS: Virtual surgery and 3D printing model combined with guide plate can ensure an accurate reduction of condylar neck fracture and simplify the operation process, which can be used as an accurate, efficient and predictable auxiliary method.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for primary hepatocellular carcinoma (PHC). Radioactive iodine therapy has been used in the treatment of advanced PHC, especially in patients with portal vein tumor thrombosis. However, data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce. AIM: To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography (CT). METHODS: For this study, 98 advanced PHC patients were recruited and divided randomly into the study and control groups. Patients in the study group were treated with TACE combined radioactive iodine implantation therapy. Patients in the control group were treated with only TACE. The tumor lesion length, clinical effect, serum alpha-fetoprotein (AFP) and CT perfusion parameters were compared before and after therapy, and statistical analysis was performed. RESULTS: There was no significant difference in tumor length and serum AFP between the study and control groups (P > 0.05) before treatment. However, the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy. After 3 mo of treatment, the complete and partial remission rate of the study group was 93.88%, which was significantly higher than the control group (77.55%) (P < 0.05). Before treatment, there were no significant differences between the two groups on the perfusion CT variables, including the lesion blood volume, permeability surface, blood flow, hepatic artery flow and mean transit time (P > 0.05). After 3 mo of treatment, all perfusion CT variables were lower in the study group compared to the control group (P < 0.05). The survival time of patients in the study group was 22 mo compared to 18 mo in the control group, which was significantly different [log rank (Mantel-Cox) = 4.318, P = 0.038]. CONCLUSION: TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions, thereby improving the clinical efficacy and prolonging the survival time of patients.

Single-cell transcriptomic characterization of sheep conceptus elongation and implantation.

Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.

Primary results of chest wall reconstruction with polydioxanone mesh on animals.

BACKGROUND: With the development of surgical techniques and biomedical material, increasing synthetic materials are applied to the chest wall reconstruction, such as autologous rib, muscle flap, bovine pericardium and sheet metal. AIM: To detect the safety and efficiency of synthetic material Polydioxanone (PDO) in chest wall reconstruction. MATERIALS AND METHODS: Healthy adult mongrel dogs operated with PDO, and then some clinical data were collected. RESULTS: Here we showed that PDO mesh could close down the function of chest wall defect, and PDO mesh could be degraded gradually and forms a fibrous layer with the surrounding tissues. Our data further demonstrated PDO mesh leads to slight lung adhesion with a small shrinkage. CONCLUSIONS: These findings thus provide the first evidence that the feasibility of PDO mesh in chest wall reconstruction in dogs.

N-(2,3,4-Trifluoro-phen-yl)morpholine-4-carboxamide.

In title mol-ecule, C(11)H(11)F(3)N(2)O(2), the central -N-C(=O)-N- unit is essentially planar [maximum deviation = 0.013 (2) Å] and forms a dihedral angle of 57.33 (9)° with the benzene ring. The morpholine ring is in a chair conformation. In the crystal, mol-ecules are linked into chains along [001] by N-H⋯O hydrogen bonds.

WITHDRAWN: Design and Evaluation of Floating Micro-Carriers for Effective Delivery of a Hydrophobic Drug

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Vision loss due to uncommon "red eye": A case report.

RATIONALE: Phacolytic glaucoma is a rare complication induced by hypermature cataracts and may occasionally be encountered in some rural areas. It tends to be misdiagnosed and induces a risk of permanent vision impairment. PATIENT CONCERNS: A 63-year-old Uighur woman complained of redness and decreased vision in her right eye and was treated for endophthalmitis at a primary hospital before being referred to our hospital. DIAGNOSIS: On admission, the patient had weak light perception in the right eye, an intraocular pressure of 65 mmHg, and slit-lamp examination revealed swelling of the eyelids and significant injection of conjunctiva. The entire cornea was cloudy and edematous, whereas the aqueous humor was milky turbid. Cytological examination of the aqueous liquid confirmed the presence of lens protein-laden macrophages. A Morgagnian cataract was observed after anterior chamber irrigation. So the final diagnosis was phacolytic glaucoma. INTERVENTIONS: The patient received anterior chamber irrigation and extracapsular cataract extraction with intraocular lens implantation successively. OUTCOMES: Final visual acuity was limited to 6/120 due to secondary optic nerve damage. LESSONS: Phacolytic glaucoma can mimic endophthalmitis and tend to be misdiagnosed, causing permanent vision impairment. Improving awareness of phacolytic glaucoma and enhancing public health education regarding cataracts are ways to prevent phacolytic glaucoma and phacolytic glaucoma-related vision loss.

Study on antibacterial effect of halicin (SU3327) against Enterococcus faecalis and Enterococcus faecium.

Enterococci are important pathogens of nosocomial infections and are increasingly difficult to treat due to their intrinsic and acquired resistance to a range of antibiotics. Therefore, there is an urgent need to develop novel antibacterial agents, while drug repurposing is a promising approach to address this issue. Our study aimed to determine the antimicrobial efficacy of halicin against enterococci and found that the minimum inhibitory concentrations (MIC) of halicin against different strains of Enterococcus faecalis and Enterococcus faecium ranged from 4 to 8 µg/ml. In addition, the synergistic antibacterial effect between halicin and doxycycline (DOX) against Enterococcus was observed through the checkerboard method, and it was observed that halicin and DOX could significantly synergistically inhibit biofilm formation and eradicate preformed biofilms at sub-MICs. Moreover, the electron microscope results revealed that halicin could also disrupt the bacterial cell membrane at high concentrations. Furthermore, it is also confirmed that the combination of halicin and DOX has no significant cytotoxic effect on erythrocytes and other human-derived cells. In addition, the mouse subcutaneous model and H&E staining showed that the combination of halicin and DOX could effectively reduce the bacterial load and inflammatory infiltration without obvious side effects. In nutshell, these results demonstrate the potential of halicin in combination with DOX as a novel therapy against infections by Enterococcus.

Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart.

The annulus fibrosis electrically insulates the atria and ventricles, allowing the timed sequential beating of these structures that is necessary for efficient heart function. Abnormal development of the annulus fibrosis leads to persistence of accessory electrical pathways from atria to ventricles, providing the anatomical substrate for re-entrant cardiac arrhythmias such as Wolff-Parkinson-White syndrome. To better understand the development of the annulus fibrosis and the etiology of these cardiac arrhythmias, we used Cre-LoxP technology to assess the contribution of epicardium derived cells (EPDCs) to the annulus fibrosis. We found that EPDCs migrated into the region of the forming annulus fibrosis, marked by the protein periostin. These EPDCs also stained positive for procollagen I, suggesting that the EPDCs themselves synthesize proteins of the annulus fibrosis. To further test the hypothesis that EPDCs contribute to cells that synthesize the annulus fibrosis, we purified genetically marked EPDCs from the atrioventricular region and measured gene expression by quantitative PCR. These EPDCs were highly enriched for mRNAs encoding periostin, procollagen I, fibronectin I, vimentin, discoidin domain receptor 2, and tenascin C, markers of fibroblasts and components of the annulus fibrosis. In addition, these EPDCs were highly enriched for Snail, Smad1, Slug, and Twist1, markers for epithelial-to-mesenchymal transition (EMT), and a metalloprotease, Mmp2, that contributes to cellular migration. Our work provides for the first time definitive evidence that epicardium contributes to formation of the mammalian annulus fibrosis through EMT. Abnormalities of this differentiation process may underlie development of some forms of re-entrant atrioventricular tachycardia.

Effect of long term glucocorticoid treatment on human growth hormone secretion in children and adolescents and the safety and effectiveness of recombinant human growth hormone treatment.

OBJECTIVE: Long term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment. METHODS: Twelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved. RESULTS: The growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (P<0.05), and then to 6.9∓0.4cm/year one year later. CONCLUSIONS: The long-term glucocorticoid treatment can decrease the hGH secretion, and thus leads to short stature and agenesis. However, the rhGH replacement can safely and effectively improve growth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.

MiR-483-5p downregulation contributed to cell proliferation, metastasis, and inflammation of clear cell renal cell carcinoma.

Inflammation status are especially for tumor growth, and microRNAs (miRNAs) confirmed to participate in cancer occurrence and progression. However, the role of miR-483-5p and the relation with inflammation have not been elucidated in renal cell cancer (RCC). In this study, we intended to explore miR-483-5p expression and the relationship of inflammation status in clear cell renal cell cancer (ccRCC). Using microarray and qRT-PCR (Quantitative Real-time Polymerase Chain Reaction), we investigated the miR-483-5p expression in plasma and ccRCC cancer tissues. Then, we analyzed the correlation of miR-483-5p with clinicopathological parameters and inflammation status in ccRCC. Receiver operator characteristic (ROC) curves analysis was used to analyze the discrimination efficiency of miR-483-5p. in vitro experiments explored the biological role of miR-483-5p in renal cancer cells. miR-483-5p expression was upregulated in plasma of 5 patients with microarray and 12 patients with qRT-PCR in ccRCC at day 7 postoperatively. In addition, low expression of miR-483-5p was found in 58 ccRCC cancer tissues when compared with non-cancerous tissues. miR-483-5p could sufficiently discriminate ccRCC with the area under the curve (AUC) of 0.739 (P < .0001) from normal tissues. Higher expression of miR-483-5p was positively related to lower tumor stage and higher relative expression of miR-483-5p was inversely related to neutrophil-to-lymphocyte ratio (NLR) (P = .03) and lymphocyte-to-monocyte ratio (LMR) (P = .026). Overexpression of miR-483-5p lead to reverse epithelial-mesenchymal transition (EMT) process, restrain cell proliferation and metastasis of renal cancer cells. Our findings suggest that miR-483-5p expression is negatively correlation with inflammation status and may be a potential plasma biomarker for ccRCC.

Effects of decabrominated diphenyl ether (PBDE 209) on voltage-gated sodium channels in primary cultured rat hippocampal neurons.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame-retardant additives. But the application of PBDEs has been challenged due to their toxicity, especially neurotoxicity. In this study, we investigated the effects of decabrominated diphenyl ether (PBDE 209), the major PBDEs product, on voltage-gated sodium channels (VGSCs) in primary cultured rat hippocampal neurons. Employing the whole-cell patch-clamp technique, we found that PBDE 209 could irreversibly decrease voltage-gated sodium channel currents (I(Na)) in a very low dose and in a concentration-dependent manner. We had systematically explored the effects of PBDE 209 on I(Na) and found that PBDE 209 could shift the activation and inactivation of I(Na) toward hyperpolarizing direction, slow down the recovery from inactivation of I(Na), and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could affect VGSCs, which may lead to changes in electrical activities and contribute to neurotoxicological damages. We also showed that ascorbic acid, as an antioxidant, was able to mitigate the inhibitory effects of PBDE 209 on VGSCs, which suggested that PBDE 209 might inhibit I(Na) through peroxidation. Our findings provide new insights into the mechanism for the neurological symptoms caused by PBDE 209.

One-Pot Hydrothermal Synthesis of g-C3N4/BiPO4 Nanocomposites with Significant Photocatalytic Activity.

The g-C3N4/BiPO4 composites have been successfully synthesized via a one-pot hydrothermal process, which can be used to degrade the organic dyes (rhodamine B and methylene blue) under simulated sunlight irradiation. X-ray diffraction (XRD), scanning electron microscope (SEM), UV-Vis diffuse reflectance spectra and Fourier transform infrared (FTIR) spectroscopy have been employed to characterize the samples. The g-C3N4/BiPO4 composites exhibited higher photocatalytic activity than pure BiPO4. And the optimum photocatalyst shows the outstanding photocatalytic activity, which exhibited 99.0% and 86.6% decolorization rate of RhB and MB, respectively.

Total bile acid-to-cholesterol ratio as a novel noninvasive marker for significant liver fibrosis and cirrhosis in patients with non-cholestatic chronic hepatitis B virus infection.

Although serum bile acids and total cholesterol (TC) are closely related to liver cirrhosis, the potential diagnostic value of total bile acid-to-cholesterol ratio (TBA/TC) for liver fibrosis is unclear. The present study aimed to evaluate the value of TBA/TC in the diagnosis of cirrhosis and the relationship between TBA/TC and significant liver fibrosis in chronic hepatitis B virus (HBV) infected patients without cholestasis.667 patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 32 patients and METAVIR scoring system was used to evaluate liver fibrosis stage. Liver ultrasound elastography was performed in 138 patients, significant fibrosis was defined as fibrosis ≥ F2. Multiple logistic regression as well as receiver operating characteristic (ROC) curves analyses were performed.Compared to patients with non-cirrhosis, TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower (all P < .001). In multivariate analysis, TBA/TC was also independently associated with cirrhosis [odds ratio (OR) = 1.102, 95% confidence interval (CI): 1.085-1.166]. The area under the curve (AUC) of TBA/TC (0.87) was almost equivalent to the aspartate aminotransferase to platelet ratio index (APRI, AUC = 0.84) and fibrosis 4 score (FIB-4, AUC = 0.80), and the optimal cut-off value for TBA/TC to diagnose cirrhosis was 2.70. Among the patients performed liver biopsy, TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage (all P < .001). Furthermore, In patients performed liver ultrasound elastography, TBA/TC was also independently associated with significant fibrosis (OR = 1.040, 95% CI: 1.001-1.078).Assessment of TBA/TC could serve as an additional marker of significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection.

Effects of sodium valproate on synaptic transmission and neuronal excitability in rat hippocampus.

1. Valproate (VPA) has long been used in the treatment of both generalized and partial seizures. However, its cellular mechanisms of action remain unclear. 2. In the present study, the effects of VPA on synaptic transmission and neuronal excitability were examined in the hippocampal CA1 region using whole-cell patch clamp recordings. 3. Perfusion with VPA, at therapeutically attainable concentrations (i.e. 0.3 and 0.6 mmol/L), significantly increased the frequency (112 +/- 2 and 133 +/- 2% of control, respectively; n = 5; both P < 0.05), but not the average amplitude, of miniature inhibitory post-synaptic currents (mIPSCs). Perfusion with VPA had no effect on either the amplitude or the frequency of miniature excitatory post-synaptic currents (mEPSCs). 4. In acutely dissociated CA1 pyramidal neurons, VPA had no effect on 10 micromol/L GABA-induced currents. Furthermore, following the administration of 0.3 and 0.6 mmol/L VPA, the frequency of action potential firing was significantly reduced from 18.0 +/- 1.1 to 15.3 +/- 0.9 and from 18.6 +/- 0.9 to 12.6 +/- 0.6, respectively (n = 8; both P < 0.05). In contrast, 0.3 and 0.6 mmol/L VPA significantly increased spike frequency adaptation from 4.02 +/- 0.47 to 4.72 +/- 0.55 and from 3.47 +/- 0.41 to 4.48 +/- 0.58, respectively (n = 8; P < 0.05). 5. The results of the present study suggest that VPA presynaptically increases inhibitory synaptic activity without modifying excitatory synaptic transmission and reduces neuronal excitability. Any or all of these effects may contribute to its anticonvulsant action.