A molecular sheaf: doubly threaded [6]rotaxane.

We report that the use of a hydrogen-bonded pyrimidine-macrocycle complex can efficiently facilitate the threading of two bispyridinium ethylenes into four rings, as evidenced by X-ray crystallography of its precursor, offering a rare example of a doubly threaded [6]rotaxane in 91% yield. The unusual architecture is found to be stable with no dethreading despite the large ring size of the macrocycle with respect to the stopper.

A comparative study on the application of different endoscopic diagnostic methods in the differential diagnosis of benign and malignant bile duct strictures.

Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures. Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events. Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis. Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage.

Two New Aluminoborates with 3D Porous-Layered Frameworks.

Two new aluminoborates, NaKCs[AlB7O13(OH)]·H2O (1) and K4Na5[AlB7O13(OH)]3·5H2O (2), have been hydro(solvo)thermally made with mixed alkali metal cationic templates. Both 1 and 2 crystallize in the monoclinic space group P21/n and contain similar units of [B7O13(OH)]6- cluster and AlO4 tetrahedra. The [B7O13(OH)]6- cluster is composed of three classical B3O3 rings by vertex sharing, of which two of them connect with AlO4 tetrahedra to constitute monolayers, and one provides an O atom as a bridging unit to link two oppositely orientated monolayers by Al-O bonds to form 3D porous-layered frameworks with 8-MR channels. UV-Vis diffuse reflectance spectra indicate that both 1 and 2 exhibit short deep-UV cutoff edges below 190 nm, revealing that they have potential applications in deep-UV regions.

40Ni-Added Poly(polyoxometalate) Assembled by {Ni6GeW9} and {Ni8(GeW9)2} Units: Structure, Magnetic, and Heterogeneous Catalysis Properties.

A novel 40Ni-added germanotungstate, Cs8K14Na3H3{[Ni6(OH)3(H2O)6(B-α-GeW9O34)]2[Ni8(µ6-O)(µ2-OH)2 (µ3-OH)2(H2O)B2O3(OH)2(B-α-GeW9O34)2]}2·84H2O (1), was made by the reaction of the trivacant [A-α-GeW9O34]10- ({GeW9}) precursor with Ni2+ cations and B5O8-, and systematically investigated by Fourier-transform infrared spectroscopy, elemental analysis, thermogravimetric analysis, and powder X-ray diffraction. Single crystal X-ray analysis indicates that the polyoxoanion of 1 is a novel octamer constructed by {Ni6GeW9} and {Ni8(GeW9)2} structural building units via Ni-O═W linkages. The magnetic behavior shows the existence of overall ferromagnetic interactions among the Ni2+ centers in compound 1. Photocatalytic H2 production studies have implied that 1 can work as a heterogeneous catalyst for hydrogen production with decent robustness and recyclability.

Efficacy and safety of covered versus uncovered self­expandable metal stents for the palliative treatment of malignant distal biliary stricture: A long­term retrospective study.

Both covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) have been tried in the palliation of malignant distal biliary strictures by means of endoscopic retrograde cholangiopancreatography (ERCP); however, the comparison of efficacy and safety between them remains contested. To the best of our knowledge, no similar studies have assessed this in the Chinese population. In the present study, the clinical and endoscopic data of 238 patients (CSEMSs, n=55; USEMSs, n=183) with malignant distal biliary strictures from 2014 to 2019 were collected. The efficacy indicated by mean stent patency, stent patency rate, mean patient survival time and survival rate, and the safety indicated by adverse events after CSEMS or USEMS placement were retrospectively analyzed and compared. The mean stent patency time was significantly longer in the CSEMSs group than that in the USEMSs group (262.8±195.3 days vs. 169.5±155.7 days, P=0.002). The mean patient survival time was significantly longer in the CSEMSs group than that in the USEMSs group (273.9±197.6 days vs. 184.9±167.6 days, P=0.003). The stent patency rate and patient survival rate were significantly higher in the CSEMSs group than those in the USEMSs group at 6 and 12 months, but not at 1 and 3 months. There was no significant difference in stent dysfunction and adverse events between the two groups, although post-ERCP pancreatitis (PEP) occurred more frequently in the CSEMSs group than in the USEMSs group (18.1% vs. 8.8%, P=0.049). In conclusion, CSEMSs were better than USEMSs for malignant distal biliary strictures in terms of stent patency time and patient survival time as well as stent patency rate and patient survival rate in the long term (>6 months). Adverse events in the two groups occurred at a similar rate, although the incidence of PEP was higher in the CSEMSs group.

Supramolecular Shish Kebabs: Higher Order Dimeric Structures from Ring-in-Rings Complexes with Conformational Adaptivity.

Use of abiotic chemical systems for understanding higher order superstructures is challenging. Here we report a ring-in-ring(s) system comprising a hydrogen-bonded macrocycle and cyclobis(paraquat-o-phenylene) tetracation (o-Box) or cyclobis(paraquat-p-phenylene) tetracation (CBPQT4+ , p-Box) that assembles to construct discrete higher order structures with adaptive conformation. As indicated by mass spectrometry, computational modeling, NMR spectroscopy, and single-crystal X-ray diffraction analysis, this ring-in-ring(s) system features the box-directed aggregation of multiple macrocycles, leading to generation of several stable species such as H4G (1 a/o-Box) and H5G (1 a/o-Box). Remarkably, a dimeric shish-kebab-like ring-in-rings superstructure H7G2 (1 a/o-Box) or H8G2 (1 a/p-Box) is formed from the coaxial stacking of two ring-in-rings units. The formation of such unique dimeric superstructures is attributed to the large π-surface of this 2D planar macrocycle and the conformational variation of both host and guest.

A {Co9}-Added Polyoxometalate for Efficient Visible-Light-Driven Hydrogen Evolution.

A polyanion cluster H6Na8Cs3[Co9(µ3-OH)3(H2O)6(HPO4)2(B-α-PW9O34)3]Cl·40H2O (1) was made with the guidance of the lacunary directing strategy under hydrothermal conditions. Compound 1 was characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermogravimetric analysis, respectively. Single-crystal X-ray diffraction analyses showed that 1 consists of three anions [B-α-PW9O34]9- and a cyclic cationic [Co9(µ3-OH)3(H2O)6]15+ and two anions HPO42-. Variable-magnetic properties indicate antiferromagnetic interactions in 1. Visible-light-driven hydrogen evolution tests demonstrated that 1 was an efficient water reduction catalyst with an H2 evolution rate of 1217.6 µmol h-1 g-1.

Chiral {Ni6PW9} Cluster-Organic Framework: Synthesis, Structure, and Properties.

A chiral three-dimensional polyoxometalate cluster-organic framework (POMCOF) H3[(btc)Ni6(µ3-OH)3(H2O)5(B-α-PW9O34)]·17H2O (1, btc = 1,2,4-benzenetricarboxylate) has been made under hydrothermal conditions in the absence of amine or chiral starting reagents. 1 shows high stability in CH3CN/DMF (1:3), acidic, and basic solutions with the pH ranging from 2 to 12 for 5 days. The UV-vis reflectance spectra and Mott-Schottky measurements reveal that 1 could be a suitable catalyst for photocatalysis. Visible-light-driven H2 evolution studies have demonstrated that 1 is an ecofriendly, efficient, and recyclable catalyst with a H2 evolution rate of 1058.24 µmol h-1g-1. Nonlinear optical (NLO) measurement reveals that 1 exhibits a second-harmonic generation (SHG) response of about 1.4 times that of KH2PO4 (KDP), indicating that 1 is a potential NLO material as well.

Meningeal carcinomatosis following a curative endoscopic submucosal dissection of early gastric cancer: a case report.

Meningeal carcinomatosis (MC) is reported to occur in 4%-15% of patients with solid tumors. MC is not commonly associated with gastric carcinoma and is extremely rare in patients with early gastric cancer (EGC). MC derived from EGC after curative endoscopic submucosal dissection (ESD) has not been reported before. We present a rare case of a 49-year-old patient who developed MC after curative ESD of EGC. The cancer was an ulcerated lesion approximately 1.0 cm in diameter in endoscopic appearance in the minor curvature of the gastric antrum. The pathological examination after ESD indicated high-grade intraepithelial neoplasia (1.3 × 2.1 cm in size) with localized moderately differentiated adenocarcinoma (0-IIc in tumor stage, intestinal type in Lauren classification), which was confined to the mucosal layer with an intact submucosal layer and muscularis propria. The lesion was removed entirely by curative dissection without vertical and horizontal resection margins involvement in pathology. Two months after ESD, the patient was readmitted for severe headache and vomiting. Cytological examination of the cerebrospinal fluid found malignant tumor cells, which were considered by pathologists to have metastasized from the stomach, further confirming MC derived from EGC. The patient's condition deteriorated dramatically, which prevented him from receiving further therapies, such as chemotherapy, and he died 3 days after the diagnosis of MC. In conclusion, EGC can cause MC, even after curative ESD. New neurological manifestations in patients with EGC can alert physicians to a diagnosis of MC, and more attention needs to be paid to evaluating the nervous system and establishing diagnostic and therapeutic strategies as soon as possible.

Challenging Diagnosis and Endoscopic Management of Dieulafoy's Lesion-Induced Small-Bowel Bleeding: A Case Report.

Small-bowel bleeding is a relatively uncommon event of gastrointestinal bleeding. Some causes of small-bowel bleeding, such as vascular lesions, are still challenging to confirm, despite the use of various diagnostic modalities (e.g., capsule endoscopy, deep enteroscopy, and radiographic imaging). Vascular lesion-induced bleeding tends to be insidious and intermittent, but sometimes it can be massive and fatal, so that the timing of an endoscopy is critical. We describe herein the case of an elderly female patient with Dieulafoy's lesion-induced small-bowel bleeding presenting with recurrent melena. In this article, we describe how the cause of her bleeding was found and how the bleeding was stopped endoscopically. Finally, we discuss the characteristics of a small-bowel Dieulafoy's lesion and its endoscopic treatment.

[Oxidative stress preconditioning alleviates oxidative stress-induced damage of bone marrow mesenchymal stem cells].

Objective To investigate the effect of oxidative stress preconditioning on the oxidative stress-induced damage of bone marrow mesenchymal stem cells (BMSCs). Methods BMSCs were isolated and cultured by density gradient centrifugation combined with adherence method. The cells were divided into three groups: control group (control medium), oxidative damage group (treated with 1000 µmol/L H2O2 for 24 hours), and preconditioning group (preincubated with 50 µmol/L H2O2 for 8 hours before treatment with 1000 µmol/L H2O2 for 24 hours). DCFH-DA staining was used to analyze the level of reactive oxygen species (ROS). Mitochondrial membrane potential was measured by JC-1 staining. DNA damage was detected by TUNEL. Malondialdehyde (MDA) content was detected by thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was detected by water soluble tetrazolium-1 (WST-1) assay. CCK-8 assay was used to detect cell viability and flow cytometry to detect cell apoptosis. Results Compared with the oxidative damage group, the preconditioning group had reduced ROS level, reduced DNA damage, higher mitochondrial membrane potential, significantly decreased MDA content, increased SOD activity, increased cell viability, and significantly decreased apoptosis. Conclusion Oxidative stress preconditioning can enhance the anti-oxidative stress ability of BMSCs and promote its survival under oxidative stress.

Biodegradation of gaseous xylene in a flat composite membrane bioreactor.

The xylene is an important hydrophobic volatile organic compound (VOC) widely used as a solvent in different industries. Compared to the conventional bioreactors, the membrane bioreactor is more efficient for the degradation of hydrophobic VOCs. In this work, the degradation of gaseous xylene in a flat composite membrane bioreactor inoculated with activated sludge under different operating conditions was investigated. The maximum elimination capacities, ECv of 289 g/(m3 h) and ECm of 0.145 g/(m2 h) were obtained at the gas residence time of 20 s and the loading rate of 475 g/(m3 h). Moreover, the membrane bioreactor is stable enough to suffer weak shock loading and short intermittent process shutdown. These results indicate that the membrane biotechnology shows great potentials in practical applications for xylene removal.

PARK7 enhances antioxidative-stress processes of BMSCs via the ERK1/2 pathway.

Oxidative stresss in the microenvironment surrounding lesions induces apoptosis of transplanted bone-marrow-derived mesenchymal stem cells (BMSCs). Hence, there is an urgent need for improving antioxidative-stress processes of transplanted BMSCs to further promote their survival. The present study reports the role and mechanism of Parkinson's disease protein 7 (PARK7) in enhancing antioxidative activity in BMSCs. We used a PARK7 lentivirus to transfect BMSCs to up- or downregulate PARK7, and then used H2 O2 to simulate oxidative stress in BMSCs in vitro. Overexpression of PARK7 effectively reduced reactive oxygen species and malondialdehyde, protected mitochondrial membrane potential, and resisted oxidative-stress-induced apoptosis of BMSCs, but the expression of PARK7 was downregulated, these results were reversed. At the same time, we also found that overexpression of PARK7 increased extracellular-regulated protein kinase 1/2 (ERK1/2) phosphorylation and nuclear translocation, as well as upregulated Elk1 phosphorylation and superoxide dismutase (SOD) expression. In contrast, when U0126 was used to block the ERK1/2 pathway, ERK1/2 and Elk1 phosphorylation levels were downregulated, ERK1/2 nuclear translocation and SOD content were significantly reduced, and PARK7-overexperssion-induced antioxidative activity was completely blocked. Collectively, our results suggest that PARK7 overexpression increased antioxidative-stress processes and survival of BMSCs subjected to H2 O2 via activating the ERK1/2 signaling pathway. Our findings may guide the development of a PARK7-specific strategy for improving the transplantation efficacy of BMSCs.

Caffeic acid polymer rapidly modified sponge with excellent anti-oil-adhesion property and efficient separation of oil-in-water emulsions.

The efficient treatment of high stability emulsion with small diameter and the prevention of oil contamination of materials are serious issues in the process of emulsion separation. In order to address those issues, we reported a fast and versatile hydrophilic surface coating technology that uses oxidants and diamines to synergistically promote the polymerization of caffeic acid (CA). It was found that amino groups can not only accelerate the polymerization of CA, but also promote the deposition of polymers on the sponge surface. Using silica nanoparticles to improve the roughness, superhydrophilic melamine sponge could be prepared, which exhibited excellent superhydrophlic-underwater superolephobic and anti-oil-adhesion properties. DFT simulation was employed to explore the potential mechanism of the anti-oil adhesion ability. In addition, combined with the mechanical compression strategy, the sponge exhibited a high efficiency of 99.10% with a permeation flux of 19080 ±â€¯700 Lm-2 h-1 in emulsion separation just under the action of gravity. Moreover, based on the interaction between the surfactant and the surface of the material, the separation mechanism was discussed. Overall, this work provided an advanced method for the preparation of superhydrophilic sponge with anti-oil-fouling performance, which showed great potential in dealing with practically challenging emulsified wastewater.

Preincubation with a low-dose hydrogen peroxide enhances anti-oxidative stress ability of BMSCs.

OBJECTIVE: To investigate the effects of low-concentration hydrogen peroxide pretreatment on the anti-oxidative stress of the bone marrow mesenchymal stem cells (BMSCs). METHODS: Rabbit BMSCs were isolated and cultured by density gradient centrifugation combined with the adherence method. Then, the third generation of well-grown BMSCs was continuously treated with 50-µM hydrogen peroxide (H2O2) for 8 h as the optimal pretreatment concentration and the BMSCs were continuously applied for 24 h with 500 µM H2O2, and the optimal damage concentration was determined as the oxidative stress cell model. The experiment was divided into three groups: control group, high-concentration H2O2 injury group (500 µM), and low-concentration H2O2 pretreatment group (50 µM + 500 µM). In each group, the DCFH-DA fluorescence probe was used to detect the reactive oxygen species (ROS). ELISA was used to detect the activity of superoxide dismutase (SOD) and catalase (CAT), and the TBA method was used to detect malondialdehyde (MDA). The mitochondrial membrane potential was detected by JC-1. The cell viability was detected by CCK-8 method, while flow cytometry and TUNEL/DAPI double staining were performed to detect cell apoptosis. Hence, the effect of H2O2 pretreatment on the anti-oxidative stress of BMSCs was investigated. One-way analysis of variance was performed using SPSS 19.0 statistical software, and P < 0.05 was considered statistically significant. RESULTS: A large number of typical BMSCs were obtained by density gradient centrifugation and adherent culture. The oxidative stress cell model was successfully established by 500-µM H2O2. Compared with the high-concentration H2O2 injury group, the low-concentration H2O2 pretreatment reduced the production of ROS [(62.33 ± 5.05), P < 0.05], SOD and CAT activities significantly increased (P < 0.05), and MDA levels significantly decreased (P < 0.05). The mitochondrial membrane potential fluorescence changes, the ratio of red/green fluorescence intensity of the high-concentration H2O2 injury group was less, and the ratio of the low-concentration H2O2 pretreatment group was significantly higher than that. The ratio of red/green increased by about 1.8 times (P < 0.05). The cell viability and survival rate of BMSCs were significantly increased in low-concentration H2O2 pretreatment group (P < 0.05), and the cell apoptosis rate was significantly decreased (P < 0.05). CONCLUSION: Pretreatment with low-concentration H2O2 can enhance the anti-oxidative stress ability and reduce their apoptosis of BMSCs under oxidative stress.

[Effects of nicotinamide mononucleotide adenylyl transferase 3 on mitochondrial function and anti-oxidative stress of rabbit bone marrow mesenchymal stem cells via regulating nicotinamide adenine dinucleotide levels].

OBJECTIVE: To investigate the effect of nicotinamide mononucleotide adenosyl transferase 3 (NMNAT3) on the mitochondrial function and anti-oxidative stress of rabbit bone marrow mesenchymal stem cells (BMSCs) under oxidative stress in vitro by regulating nicotinamide adenine dinucleotide (NAD +) levels. METHODS: The bone marrow of femur and tibia of New Zealand white rabbits were extracted. BMSCs were isolated and cultured in vitro by density gradient centrifugation combined with adherent culture. The third generation cells were identified by flow cytometry and multi-directional induction. Overexpression of NMNAT3 gene was transfected into rabbit BMSCs by enhanced green fluorescent protein (EGFP) labeled lentivirus (BMSCs/Lv-NMNAT3-EGFP), and then the expression of NMNAT3 was detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot and cell proliferation by cell counting kit 8 (CCK-8) method. BMSCs transfected with negative lentivirus (BMSCs/Lv-EGFP) and untransfected BMSCs were used as controls. The oxidative stress injury cell model was established by using H 2O 2 to treat rabbit BMSCs. According to the experimental treatment conditions, they were divided into 4 groups: Group A was normal BMSCs without H 2O 2 treatment; untransfected BMSCs, BMSCs/Lv-EGFP, and BMSCs/Lv-NMNAT3-EGFP in groups B, C, and D were treated with H 2O 2 simulated oxidative stress, respectively. The effects of NMNAT3 on the mitochondrial function of BMSCs under oxidative stress [changes of mitochondrial membrane potential, NAD + and adenosine triphosphate (ATP) levels], the changes of anti-oxidative stress ability of BMSCs [reactive oxygen species (ROS) and malondialdehyde (MDA) levels, manganese superoxide dismutase (Mn-SOD) and catalase (CAT) activities], and the effects of BMSCs on senescence and apoptosis [senescence associated-ß-galactosidase (SA-ß-gal) staining and TUNEL staining] were detected after 24 hours of treatment. RESULTS: The rabbit BMSCs were successfully isolated and cultured in vitro. The stable strain of rabbit BMSCs with high expression of NMNAT3 gene was successfully obtained by lentiviral transfection, and the expressions of NMNAT3 gene and protein significantly increased ( P<0.05). There was no significant difference in the trend of cell proliferation compared with normal BMSCs. After treatment with H 2O 2, the function of mitochondria was damaged and apoptosis increased in all groups. However, compared with groups B and C, the group D showed that the mitochondrial function of BMSCs improved, the membrane potential increased, the level of NAD + and ATP synthesis of mitochondria increased; the anti-oxidative stress ability of BMSCs enhanced, the levels of ROS and MDA decreased, and the activities of antioxidant enzymes (Mn-SOD, CAT) increased; and the proportion of SA-ß-gal positive cells and the rate of apoptosis decreased. The differences in all indicators between group D and groups B and C were significant ( P<0.05). CONCLUSION: NMNAT3 can effectively improve the mitochondrial function of rabbit BMSCs via increasing the NAD + levels, and enhance its anti-oxidative stress and improve the survival of BMSCs under oxidative stress conditions.

Functional group-rich hyperbranched magnetic material for simultaneous efficient removal of heavy metal ions from aqueous solution.

In order to achieve the purpose of simultaneous removal of coexisting heavy metal ions, in this work, functionalized magnetic mesoprous nanomaterials (Fe3O4-HBPA-ASA) with high density and multiple adsorption sites were designed and prepared. The obtained Fe3O4-HBPA-ASA was characterized by SEM, FTIR, VSM, TGA and zeta potential. Cu(II), Pb(II) and Cd(II) were chosen as the model heavy metal ions, the adsorption experiments showed that Fe3O4-HBPA-ASA showed hightheoretical adsorption capacitiesin individual system, and the maximum adsorption capacity was 136.66 mg/g, 88.36 mg/g and 165.46 mg/g, respectively. In the binary and ternary systems, the competitive adsorption leads to a decrease in the adsorption capacity of Cu(II), Pb(II) and Cd(II). However, in the ternary system with a concentration lower than 15 mg/L, the simultaneous removal rate was still higher than 90%. The adsorption isotherms and kineticswere well fitted by Langmuir and pseudo-second-order models, respectively. The XPS and density functional theory (DFT) analysis have confirmed that the adsorption of metal ions was related to various types of functional groups on the surface of Fe3O4-HBPA-ASA, while the adsorption mechanisms of Cu(II), Cd(II) and Pb(II) were different.

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning.

Clinically, bone marrow mesenchymal stem cells (BMSCs) have been used in treatment of many diseases, but the local oxidative stress (OS) of lesion severely limits the survival of BMSCs, which reduces the efficacy of BMSCs transplantation. Therefore, enhancing the anti-OS stress ability of BMSCs is a key breakthrough point. Preconditioning is a common protective mechanism for cells or body. Here, the aim of this study was to investigate the effects of OS preconditioning on the anti-OS ability of BMSCs and its mechanism. Fortunately, OS preconditioning can increase the expression of superoxide dismutase, catalase, NQO1, and heme oxygenase 1 through the nuclear factor erythroid 2-related factor 2 pathway, thereby decreased the intracellular reactive oxygen species (ROS) levels, relieved the damage of ROS to mitochondria, DNA and cell membrane, enhanced the anti-OS ability of BMSCs, and promoted the survival of BMSCs under OS.

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population.

Phenylketonuria (PKU) is a common autosomal recessive disorder of phenylalanine metabolism and mainly results a deficiency of phenylalanine hydroxylase gene (PAH). The incidence of various PAH mutations have race and ethnicity differences. We report a spectrum of PAH mutations complied from 35 PKU children who are all Chinese Han population from north Jiangsu in this study. All 13 exons and their flanking intron sequences of PAH were determined by Ion Torrent PGM™ sequencing. The relationship of genotype and phenotype was analyzed based on the sum of the arbitrary value (AV) values of the two alleles. We identified 61 mutations, with a frequency of 87.14%, among 70 alleles of 35 patients. The most prevalent mutations were R243Q (26.23%), R241C (9.84%) and V399V (8.20%). Furthermore, the consistency between prediction of the biochemical phenotype and the observed phenotype was 81.25%, with the highest consistency observed in classic PKU (87.50%). A significant correlation was found between pretreatment levels of phenylalanine and AV sum (r = -0.87, P < 0.05). Finally, our study constructs PAH mutation spectrum by next generation sequencing (NGS), and reveals that the PAH genotypes and biochemical phenotypes were significantly correlated. These offers facilitate the provision of appropriate genetic counseling for PKU patients.