Recognition Receptor for Methylated Arginine at the Single Molecular Level.

Among the various types of post-translational modifications (PTMs), methylation is the simple functionalized one that regulates the functions of proteins and affects interactions of protein-protein and protein-DNA/RNA, which will further influence diverse cellular processes. The methylation modification has only a slight effect on the size and hydrophobicity of proteins or peptides, and it cannot change their net charges at all, so the methods for recognizing methylated protein are still limited. Here, we designed a recognition receptor consisting of a α-hemolysin (α-HL) nanopore and polyamine decorated γ-cyclodextrin (am8γ-CD) to differentiate the methylation of peptide derived from a heterogeneous nuclear ribonucleoprotein at the single molecule level. The results indicate that the modification of a methyl group enhances the interaction between the peptide and the recognition receptor. The results of molecular simulations were consistent with the experiments; the methylated peptide interacts with the receptor strongly due to the more formation of hydrogen bonds. This proposed strategy also can be used to detect PTM in real biological samples and possesses the advantages of low-cost and high sensitivity and is label-free. Furthermore, the success in the construction of this recognition receptor will greatly facilitate the investigation of pathogenesis related to methylated arginine.

Systemic immune-inflammation index (SII) but not platelet-albumin-bilirubin (PALBI) grade is associated with severity of acute ischemic stroke (AIS).

INTRODUCTION: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the severity of stroke have been reported. Systemic immune-inflammation index (SII) and platelet-albumin-bilirubin (PALBI) grade as new markers of inflammation have shown their positive association with liver cancer. The relation between SII, or PALBI and stroke remains uncertain. OBJECTIVE: To investigate the relationship between SII, PALBI grade and stroke severity. METHODS: Patients with ischemic stroke with hospital admission <24 h after symptom onset were prospectively included in a stroke registry. Demographic, clinical, and laboratory data were collected immediately after admission in all patients. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Minor stroke was defined as NIHSS score < =5, moderate-to-severe stroke as NIHSS score >5. SII, calculated as platelet × neutrophil/lymphocyte was divided into four groups according to interquartile range: lowest SII (SII < 353.9 × 109/L), low SII (353.9-532.8 × 109/L), high SII (532.8-783.9 × 109/L), and highest SII (>783.9 × 109/L) group. RESULTS: A total of 362 patients with ischemic stroke were included, and between minor and moderate-to-severe stroke significant difference was found in SII (p < 0.0001), NLR (p < 0.0001), and PLR (p = 0.001), respectively. After multivariate regression analyses, SII groups (Odd ratio = 1.351, 95% confidence interval 1.084-1.684, p = 0.007) not PALBI was an independent risk factor for stroke severity. CONCLUSION: We found that SII but not PALBI, which both are markers of inflammation, was independently associated with stroke severity.

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.

Disrupted Time-Dependent and Functional Connectivity Brain Network in Alzheimer's Disease: A Resting-State fMRI Study Based on Visibility Graph.

BACKGROUND: Alzheimer's Disease (AD) is a progressive neurodegenerative disease with insidious onset, which is difficult to be reversed and cured. Therefore, discovering more precise biological information from neuroimaging biomarkers is crucial for accurate and automatic detection of AD. METHODS: We innovatively used a Visibility Graph (VG) to construct the time-dependent brain networks as well as functional connectivity network to investigate the underlying dynamics of AD brain based on functional magnetic resonance imaging. There were 32 AD patients and 29 Normal Controls (NCs) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. First, the VG method mapped the time series of single brain region into networks. By extracting topological properties of the networks, the most significant features were selected as discriminant features into a supporting vector machine for classification. Furthermore, in order to detect abnormalities of these brain regions in the whole AD brain, functional connectivity among different brain regions was calculated based on the correlation of regional degree sequences. RESULTS: According to the topology abnormalities exploration of local complex networks, we found several abnormal brain regions, including left insular, right posterior cingulate gyrus and other cortical regions. The accuracy of characteristics of the brain regions extracted from local complex networks was 88.52%. Association analysis demonstrated that the left inferior opercular part of frontal gyrus, right middle occipital gyrus, right superior parietal gyrus and right precuneus played a tremendous role in AD. CONCLUSION: These results would be helpful in revealing the underlying pathological mechanism of the disease.

Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

BACKGROUND: Bone homeostasis is a tightly orchestrated process maintained by osteoblasts and osteoclasts, and a disruption of their steady-state equilibrium can lead to the occurrence of osteoporosis (OP). METHODS: We investigated the differential expression of micro (mi)RNAs in the bone tissues of a postmenopausal osteoporosis rat model induced by ovariectomy (OVX). Real-time PCR was used to verify the differentially expressed miRNAs in bone samples from OP patients and controls. The specific targets of two differentially expressed miRNAs in osteogenic or osteoclast differentiation were determined by bioinformatic prediction, and mRNA and protein detection. RESULTS: miR-708-5p and miR-708-3p were highly expressed in the bone tissue of OVX rats and OP patients. miR-708-5p negatively regulated osteoblast differentiation in bone marrow mesenchymal stem cells by targeting SMAD specific E3 ubiquitin protein ligase 2, while miR-708-3p positively regulated osteoclast differentiation in bone marrow monocytes by targeting cerebellar degeneration associated protein 1 antisense RNA. miR-708-5p and miR-708-3p were shown to originate from the same precursor miRNA and to have a synergistic effect on the development of osteoporosis with different temporal and spatial patterns. CONCLUSION: Our findings provide a referential theoretical basis and targets for the prevention and treatment of osteoporosis.

[Comparison of laparoscopic pyelolithotomy and percutaneous nephrolithotomy for renal pelvic stones larger than 2.5 cm].

OBJECTIVE: To compare the safety, efficacy and complications of laparoscopic pyelolithotomy (LPL) and percutaneous nephrolithotomy (PCNL) for treatment of renal pelvic stones larger than 2.5 cm. METHODS: From 2011 to 2016, 32 patients underwent LPL and another 32 patients received PCNL for renal pelvic stones larger than 2.5 cm. The baseline characteristics of the patients, stone size, mean operative time, estimated blood loss, postoperative hospital stay, stone-free rate, postoperative analgesia, blood transfusion, and the intraoperative, early postoperative and long-term complications were compared between the two groups. RESULTS: The baseline characteristics and stone size were comparable between the two groups. The mean operative time of LPL and PCNL was 117∓23.12 and 118.16∓25.45 min, respectively (P>0.05). The two groups showed significant differences in the mean estimated blood loss (63∓11.25 vs 122∓27.78 mL, P<0.01) and blood transfusion rate (0 vs 6.2%, P<0.01) but not in postoperative hospital stay (4.5∓1.34 vs 4.8∓2.2 days, P>0.05), stone-free rate (93.1% vs 87.5%, P>0.05) or the postoperative analgesia time (1.7∓0.5 and 1.9∓0.6 days, P>0.05). The incidence of intraoperative complications were significant lower in LPL group than in PCNL group (6.2% vs 25.0%, P<0.01), but the incidences of early postoperative complications (25.0% vs 34.4%, P>0.05) and long-term postoperative complications (9.4% vs 12.5%, P>0.05) were similar between them. CONCLUSION: PCNL is the standard treatment for pelvic stones larger than 2.5 cm, but for urologists experienced with laparoscopic technique, LPL provides a feasible and safe option for management of such cases.

Comparisons of negative pressure wound therapy and ultrasonic debridement for diabetic foot ulcers: a network meta-analysis.

OBJECTIVE: a network meta-analysis was performed to compare the strength and weakness of negative pressure wound therapy (NPWT) with ultrasound debridement (UD) as for diabetic foot ulcers (DFU). METHODS: PubMed, Ovid EMBASE, Web of Science, Cochrane library databases, and Chinese Biomedical Literature Database were searched till February 2015. Clinical compared studies of negative pressure wound therapy and ultrasound debridement were enrolled. The primary efficacy outcomes included healed ulcers, reduction of ulcer areas and time to closure. Secondary amputation including major and minor amputations was used to assess the safety profile. RESULTS: Out of 715 studies, 32 were selected which enrolled 2880 diabetic patients. The pooled analysis revealed that NPWT including vacuum assisted closure (VAC) and vacuum sealing drainage (VSD) were as efficacious as ultrasound debridement improving healed ulcers, odds ratio, 0.86; 95% CI 0.28 to 2.6 and 1.2; 95% CI 0.38 to 4, respectively. However, both were better to standard wound care in wound healing patients. Compared with the standard wound care treated diabetic foot ulcers, NPWT and UD resulted in a significantly superior efficacy in time to wound closure and decrement in area of wound. No significances were observed between NPWT and UD groups in both indicators. Fewer patients tended to receive amputation in NPWT and UD groups compared to standard wound care group. CONCLUSIONS: The results of the network meta-analysis indicated that negative pressure wound therapy was similar to ultrasound debridement for diabetic foot ulcers, but better than standard wound care both in efficacy and safety profile.

Fiberoptic bronchoscopy-assisted endotracheal intubation in a patient with a large tracheal tumor.

In the event of a high degree of airway obstruction, endotracheal intubation can be impossible and even dangerous, because it can cause complete airway obstruction, especially in patients with high tracheal lesions. However, a smaller endotracheal tube under the guidance of a bronchoscope can be insinuated past obstructive tumor in most noncircumferential cases. Here we report a case of successful fiberoptic bronchoscopy-assisted endotracheal intubation in a patient undergoing surgical resection of a large, high tracheal tumor causing severe tracheal stenosis. A 42-year-old Chinese man presented with dyspnea, intermittent irritable cough, and sleep deprivation for one and a half years. X-rays and computed tomography scan of the chest revealed an irregular pedunculated soft tissue mass within the tracheal lumen. The mass occupied over 90% of the lumen and caused severe tracheal stenosis. Endotracheal intubation was done to perform tracheal tumor resection under general anesthesia. After several failed conventional endotracheal intubation attempts, fiberoptic bronchoscopy-assisted intubation was successful. The patient received mechanical ventilation and then underwent tumor resection and a permanent tracheostomy. This case provides evidence of the usefulness of the fiberoptic bronchoscopy-assisted intubation technique in management of an anticipated difficult airway and suggests that tracheal intubation can be performed directly in patients with a tracheal tumor who can sleep in the supine position, even if they have occasional sleep deprivation and severe tracheal obstruction as revealed by imaging techniques.