Modular Customization and Regulation of Metal-Organic Frameworks for Efficient Membrane Separations.

Metal-organic frameworks (MOFs) are considered ideal membrane candidates for energy-efficient separations. However, the MOF membrane amount to date is only a drop in the bucket compared to the material collections. The fabrication of an arbitrary MOF membrane exhibiting inherent separation capacity of the material remains a long-standing challenge. Herein, we report a MOF modular customization strategy by employing four MOFs with diverse structures and physicochemical properties and achieving innovative defect-free membranes for efficient separation validation. Each membrane fully displays the separation potential according to the MOF pore/channel microenvironment, and consequently, an intriguing H2 /CO2 separation performance sequence is achieved (separation factor of 1656-5.4, H2 permeance of 964-2745 gas permeation unit). Taking advantage of this strategy, separation performance can be manipulated by a non-destructive modification separately towards the MOF module. This work establishes a universal full-chain demonstration for membrane fabrication-separation validation-microstructure modification and opens an avenue for exclusive customization of membranes for important separations.

Structure Regulation of MOF Nanosheet Membrane for Accurate H2 /CO2 Separation.

High-purity H2 production accompanied with a precise decarbonization opens an avenue to approach a carbon-neutral society. Metal-organic framework nanosheet membranes provide great opportunities for an accurate and fast H2 /CO2 separation, CO2 leakage through the membrane interlayer galleries decided the ultimate separation accuracy. Here we introduce low dose amino side groups into the Zn2 (benzimidazolate)4 conformation. Physisorbed CO2 served as interlayer linkers, gently regulated and stabilized the interlayer spacing. These evoked a synergistic effect of CO2 adsorption-assisted molecular sieving and steric hinderance, whilst exquisitely preserving apertures for high-speed H2 transport. The optimized amino membranes set a new record for ultrathin nanosheet membranes in H2 /CO2 separation (mixture separation factor: 1158, H2 permeance: 1417 gas permeation unit). This strategy provides an effective way to customize ultrathin nanosheet membranes with desirable molecular sieving ability.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

A Genetic Variant of the ROBO3 Gene is Associated With Adolescent Idiopathic Scoliosis in the Chinese Population.

STUDY DESIGN: A case-control association study. OBJECTIVES: This study aimed to reveal whether mutations within roundabout receptor 3 ( ROBO3 ) gene were related to adolescent idiopathic scoliosis (AIS) in Chinese Han population and to investigate the functional role of ROBO3 in the pathogenesis and progression of AIS. SUMMARY OF BACKGROUND DATA: ROBO3 is essential for the regulation of hindbrain axonal cell migration and midline crossing. Studies have demonstrated that ROBO3 homozygous mutations are associated with horizontal gaze palsy with progressive scoliosis. However, whether and how ROBO3 contributed to the development of scoliosis remains unclear. MATERIALS AND METHODS: Whole exome sequencing was performed in 135 AIS patients and 267 healthy controls to evaluate the differences of single nucleotide polymorphism variants within ROBO3 . Then the identified variant of ROBO3 was genotyped in another cohort included 1140 AIS patients and 1580 controls. Moreover, paraspinal muscles were collected from 39 AIS patients and 45 lumbar disk herniation patients for the measurement of ROBO3 mRNA expression. The χ 2 test, Fisher exact test or the Student t test were used to compare intergroup data. Pearson correlation was used to determine the association between ROBO3 expression and clinical phenotypes. RESULTS: A significant association was identified between the gene variant (rs74787566) of ROBO3 and the development of AIS through exome sequencing. The genotyping cohort demonstrated a higher frequency of allele A in AIS patients compared to controls (7.89% vs . 4.30%, P <0.001, odds ratio=1.87). In addition, the expression of ROBO3 in paraspinal muscles was inversely correlated with the Cobb angle ( P =0.043, r2 =0.1059). CONCLUSION: A significant association was identified between the gene variant (rs74787566) of ROBO3 and the development of AIS. The reduced expression of ROBO3 could result in the progression of curve magnitude in patients with AIS. Further studies are needed to verify the functional role of ROBO3 in the development of AIS. LEVEL OF EVIDENCE: Level III.

Assessment of Genetic Diversity of the Salangid, Neosalanx taihuensis, Based on the Mitochondrial COI Gene in Different Chinese River Basins.

The salangid Neosalanx taihuensis (Salangidae) is a commercially important economical fish endemic to China and restricted to large freshwater systems with a wide-ranging distribution. This fish species has continuous distribution ranges and a long-introduced aquaculture history in Chinese basins. However, the research on its population genetic differentiation within and between basins is very limited. In this regard, 197 individuals were sampled from 11 populations in the Nenjiang River Basin (A1-A4), Songhua River Basin (B1), Yellow River Basin (C1-C2), Yangtze River Basin (D1), Lanchang River Basin (E1-E2) and Huaihe River Basin (F1). Based on the COI sequence, the N.taihuensis population's genetic difference within and between river basins was investigated. The haplotypes and their frequency distributions were strongly skewed, with most haplotypes (n = 13) represented only in single samples each and thus restricted to a single population. The most common haplotype (H4, 67/197) was found in all individuals. The analysis of molecular variance (AMOVA) revealed a random pattern in the distribution of genetic diversity, which is inconsistent with contemporary hydrological structure. The mismatch between the distribution and neutrality tests supported the evidence of a population expansion, which occurred during the late Pleistocene (0.041-0.051 million years ago). Significant levels of genetic subdivision were detected among populations within basins rather than between the six basins. Population history dynamics showed that N. taihuensis experienced an expansion during the glacial period in the late Pleistocene. Therefore, different populations should be considered as different management units to achieve effective conservation and management purposes. These results have great significance for the evaluation and exploitation of the germplasm resources of N. taihuensis.

Efficacy Assessment of Phentolamine Accompanied by Lidocaine Subcutaneously under Ultrasound Guidance on Radial Artery Catheterization in Pediatric Patients.

Objective: Pediatric patients are facing greater difficulties in radial catheterization for anatomic variation and smaller diameter. This study is to investigate the efficacy of phentolamine accompanied by lidocaine subcutaneously under ultrasound guidance on radial catheterization in pediatric patients. Methods: 66 pediatric patients were enrolled and randomly divided into saline group, phentolamine group, and phentolamine+lidocaine group. Baseline characteristics and surgical types were collected. Relevant solutions were subcutaneously injected, and catheterization was subsequently conducted under ultrasound guidance. Radial artery diameter and depth were measured, the success rate of catheterization and procedure time were calculated, and the complications were evaluated with ultrasonography. Results: No significant differences were observed in age, sex, weight, American Society of Anesthesiologists' classification, systolic blood pressure, diastolic blood pressure, heart rate, hemoglobin, and surgical types among three groups. Subcutaneously, the diameter in phentolamine and phentolamine+lidocaine groups increased significantly compared with the saline group. Moreover, the diameter also increased significantly after injection compared with that before injection both in the phentolamine and phentolamine+lidocaine groups. The first-attempt success rates were significantly higher while the procedure times of cannulation were shorter in the phentolamine and phentolamine+lidocaine groups than that in the saline group. Kaplan-Meier analysis showed that the overall procedure time was shorter in the phentolamine and phentolamine+lidocaine groups than the saline group. Overall complications and vasospasm incidence were lower in the phentolamine and phentolamine+lidocaine groups than the saline group. Conclusion: Phentolamine accompanied by lidocaine subcutaneous injection under ultrasound guidance improved the first-attempt success rate and reduced the complication of radial artery catheterization in pediatric patients.

Flexible Soft-Solid Metal-Organic Framework Composite Membranes for H2 /CO2 Separation.

The development of a facile strategy to construct defect-free and flexible metal-organic framework (MOF)-based membranes with high selectivity and good scalability holds great appeal. Here we report the fabrication of soft-solid MOF composite membranes on polyvinylidene fluoride substrates. A representative membrane comprised of quasi-vertically grown lamellar Zn2 (Bim)4 (Bim=benzimidazolate) and lateral ultrathin polyamide film adhering to the MOF side facets. The straight interlayer galleries within unwrapped Zn2 (Bim)4 acted as predominant pathways, while the polyamide served the function of defect elimination, synergistically inducing an unprecedented H2 /CO2 selectivity of 1084 which set a new record for MOF-based membranes. Separation performance was held constant after membrane rolling up into a tube with a diameter of 3 mm or folding and unfolding at 90° for 50 times. ZIF-67 and ZIF-8 composite membranes based on this strategy also realized extremely high H2 /CO2 separation accuracies. These results, which demonstrate the intrinsic molecular sieving capability of MOFs, will promote the development of MOF-based membranes in practical separation applications.

FOS/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis, high intestinal permeability and systemic inflammation in mice.

BACKGROUND: Obesity and osteoporosis frequently coexist, and might have a causal relationship. Gut microbiota, associated with both lipid and bone metabolism, plays an important role in the pathogenesis of excessive fat accumulation and bone loss. The improvement of intestinal flora by prebiotics was a promising strategy for ameliorating obesity-related bone loss. METHODS: Obesity model was established by feeding mice with high fat diet (HFD) for 16 weeks. Fructooligosaccharides (FOS) and/or galactooligosaccharides (GOS) were daily gavaged to mice. Osteoblastic, adipocytic, and osteoclastic differentiation was performed on primary cells isolated from experimental mice. The composition of gut flora was evaluated by 16s rDNA sequencing. Expression of intestinal junction proteins was assessed by qPCR and immunohistochemistry. Cytokine levels were measured by qPCR. RESULTS: Long-term HFD caused decreased bone mass in mice, which was associated with decreased osteogenesis, increased osteoclastogenesis, and excessive adipogenesis. FOS/GOS treatment significantly alleviated HFD-induced bone loss and reversed the imbalanced differentiation of osteoblasts, adipocytes, and osteoclasts. In addition, our study showed that FOS/GOS administration ameliorated microbiota dysbiosis (manifested as enhanced Firmicutes:Bacteriodetes ratio and reduced biodiversity), downregulated expression of intestinal junction proteins (including Claudin1, Claudin15, ZO-1, and JAM-A), and increased inflammatory cytokines (including TNFα, IL6, and IL17) in HFD-fed mice. CONCLUSION: Long-term HFD led to decreased bone mass, with microbiota dysbiosis, leaky gut, and systemic inflammation. The administration of FOS/GOS could significantly increase biodiversity and SCFA concentrations of intestinal flora in HFD fed mice, then reverse high gut permeability and inflammatory cytokines, in the end protect against HFD induced osteopenia.

The Herbal Cocktail GSYJ Attenuated Airway Inflammatory Cell Infiltration in a Chronic Asthmatic Mouse Model.

This study explored the potential therapeutic efficacy of GSYJ in attenuating asthma symptom severity and aimed to determine the immunomodulatory mechanism of GSYJ. A mouse model of chronic asthma induced by repeated Dermatophagoides pteronyssinus (Der p) challenge was established. In addition, 30 minutes before Der p challenge, the mice were orally administered GSYJ (1 g/kg). The mice were sacrificed to evaluate inflammatory cell infiltration, collagen deposition in the lung, total IgE in serum, and expression profiles of various cytokines in bronchoalveolar lavage fluid (BALF) and various genes in lung tissue. Furthermore, 30 minutes after the addition of GSYJ to RAW264.7 cell cultures, 100 ng/ml LPS was added to evaluate the effect of the drug on the LPS-induced expression of genes, proteins, and transcription factors. GSYJ may regulate transcription factors (cJUN/IRF3/NF-κB) to decrease the expression of IL-1ß, IL-6, RANTES, and iNOS in macrophages and affect the IL-12, IFN-γ, IL-5, and IL-6 levels in the BALF of mice to relieve asthma symptoms, such as inflammatory cell infiltration, hyperresponsiveness, and increased serum total IgE levels. Therefore, GSYJ has the potential to be developed into a drug treatment for chronic asthma.

Transcriptome changes of Takifugu obscurus liver after acute exposure to phenanthrene.

Phenanthrene (Phe) is a model compound in polycyclic aromatic hydrocarbon (PAH) research. Reportedly, Phe treatment induced oxidative stress and histological disorders to Takifugu obscurus liver. In this study, to further explore the molecular responses of T. obscurus liver to Phe exposure, transcriptome sequencing was applied to compare mRNA transcription profiles between Phe treatment and the control. Compared with the control, 1,581 and 1,428 genes were significantly upregulated and downregulated in Phe treatment, respectively. Further analysis revealed that Phe treatment mainly upregulated genes in Ras-MAPK and PI3K-akt signaling pathways, which represented insulin resistance and further activated the FOXO signaling pathway. The triacylglycerol biosynthesis was promoted but the gluconeogenesis process was inhibited in response to Phe treatment, demonstrating that Phe exposure disturbed the sugar and lipid metabolism. Moreover, Phe treatment upregulated the Apelin-APJ and ErbB signaling pathways, promoting angiogenesis in T. obscurus liver. Insulin resistance, promoted triacylglycerol biosynthesis, and angiogenesis might explain the molecular mechanisms underlying carcinogenic toxicity of Phe. Overall, this study provides new insights to understand the environmental risk of Phe to fishes.

An Albumin-Based Therapeutic Nanosystem for Photosensitizer/Protein Co-Delivery to Realize Synergistic Cancer Therapy.

Oxygen-dependent photodynamic therapy (PDT) is hindered by the limited availability of endogenous oxygen in solid tumors and low tumor accumulation of photosensitizers. Herein, we developed a biocompatible cancer-targeted therapeutic nanosystem based on cRGD conjugated bovine serum albumin (CBSA) co-loaded with a photosensitizer (chlorin e6, Ce6) and a therapeutic protein (cytochrome c, Cytc) for synergistic photodynamic and protein therapy. The nanosystem (Ce6/Cytc@CBSA) can target αVß3 integrin overexpressed cancer cells to improve tumor accumulation due to incorporation of cRGD. In the intracellular environment, Ce6 is released to produce toxic singlet oxygen upon near-infrared irradiation. At the same time, the therapeutic protein, Cytc, can induce programmed cell death by activating the downstream caspase pathway. Most importantly, Cytc with the catalase-like activity accelerates O2 generation by decomposing excess H2O2 in cancer cells, thereby relieving the PDT-induced hypoxia to enhance therapeutic efficacy. Both in vitro and in vivo studies reveal the significantly improved antitumor effects of the combined photodynamic/protein therapy, indicating that Ce6/Cytc@CBSA shows great potential in synergetic cancer treatments.

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes.

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

Alterations of sagittal alignment and thoracic cage parameters after long-term bracing in adolescents with idiopathic scoliosis.

BACKGROUND: Sagittal alignment and thoracic cage parameters are correlated with the surgery success rate and life quality of adolescents with idiopathic scoliosis (AIS). However, the effects of the long-term bracing on sagittal and thoracic cage parameters have not been clearly recognized. HYPOTHESIS: Long-term brace treatment could compromise sagittal balance and thoracic development in patients with AIS. PATIENTS AND METHODS: Two hundred and seventy-five patients with AIS were included in this study. The radiographs when AIS was diagnosed and 2 years after Chêneau bracing treatment were collected. Sagittal, cervical, pelvic, and thoracic cage parameters were evaluated. In addition, 32 patients finishing brace treatment with complete radiograph data were selected from included 275 patients and the data of CL, TK and LL at five different time points was collected. RESULTS: CL (average: from 14.13° to 8.94°, p=0.012), TK (average: from 24.35° to 19.02°, p=0.001) and LL (average: from 38.44° to 32.13°, p=0.004) underwent observably decline after two-year brace treatment. No statistically significant alteration of pelvic parameters was shown. The vertical parameters of thoracic cage including T1-12 height, left and right thorax height and thoracic transverse diameter increased significantly. Thoracic anteroposterior diameter at the T7 vertebral level (average: from 11.49 to 10.57cm, p=0.001) and diaphragm level (average: from 11.89 to 10.74cm, p=0.001) decreased significantly after bracing. DISCUSSION: CL, TK and LL decreased after long-term bracing treatment, which lead to the aggravation of "flat back" in AIS patients. In addition, the thoracic anteroposterior diameters declined after two-year bracing, which may result from reduced TK and contribute to further pulmonary function impairment. LEVEL OF EVIDENCE: IV.

Alkali-Etched Ni(II)-Based Metal-Organic Framework Nanosheet Arrays for Electrocatalytic Overall Water Splitting.

The exploration of efficient electrocatalysts is the central issue for boosting the overall efficiency of water splitting. Herein, pertinently creating active sites and improving conductivity for metal-organic frameworks (MOFs) is proposed to tailor electrocatalytic properties for overall water splitting. An Ni(II)-MOF nanosheet array is presented as an ideal material model and a facile alkali-etched strategy is developed to break its NiO bonds accompanied with the introduction of extra-framework K cations, which contribute to creating highly active open metal sites and largely improving the electrical conductivity. As a result, the assembled defect-Ni-MOF||defect-Ni-MOF electrolyte cell delivers a lower and stable voltage of 1.50 V at 10 mA cm-2 in alkaline medium for overall water splitting, comparable to the combination of iridium and platinum as benchmark catalysts.

miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway.

Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.

Aptamer/Peptide-Functionalized Genome-Editing System for Effective Immune Restoration through Reversal of PD-L1-Mediated Cancer Immunosuppression.

Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR-Cas9 plasmid for ß-catenin knockout to reverse tumor immunosuppression is constructed. The multi-functionalized delivery vector is decorated with aptamer-conjugated hyaluronic acid and peptide-conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT-NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective ß-catenin knockout and suppress Wnt/ß-catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death-ligand 1 (PD-L1) downregulation in edited tumor cells not only releases the PD-1/PD-L1 brake to improve the cancer killing capability of CD8+ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti-tumor immunity.

Modified C7 pedicle subtraction osteotomy for the correction of cervicothoracic kyphosis.

BACKGROUND: Osteotomies in the cervical spine are technically challenging. The purpose of this study was to evaluate the feasibility of the modified pedicle subtraction osteotomy (PSO) technique at C7 to be used for the treatment of cervicothoracic kyphosis secondary to ankylosing spondylitis. METHODS: A total of 120 cervical spine computed tomography (CT) scans (of 82 male and 38 female patients) were evaluated. The scans were taken parallel to the middle sagittal plane and the sagittal plane intersecting the pedicles. Simulated osteotomy was performed by setting the apex of the wedge osteotomy at different points, and morphologic measurements were obtained. Seven patients with cervicothoracic kyphosis who underwent a modified PSO at C7 between May 2009 and June 2015 were retrospectively evaluated. The mean follow up was 32.9 months (range 21-54 months). Preoperative and postoperative chin-brow vertical angle (CBVA), sagittal vertical axis (SVA) and sagittal Cobb angle of the cervical region were reviewed. The outcomes were analyzed through various measures, which included the 36-Item Short Form Health Survey (SF-36) and a visual analog scale for neck pain. RESULTS: In this morphometric study, a modified PSO was performed on 87 patients (59 male and 28 female) with a reasonable ratio of 72.5%. In the case series, radiographic parameters and health-related quality-of-life measures were found to show significant postoperative improvement in all patients. No major complications occurred, and no implant failures were noted until the latest follow up. CONCLUSIONS: The modified PSO is a safe and valid alternative to the classic PSO, allowing for excellent correction of cervical kyphosis and improvement in health-related quality-of-life measures.

Biotinylated and fluorophore-incorporated polymeric mixed micelles for tumor cell-specific turn-on fluorescence imaging of Al3.

Excessive amounts of Al3+ in the human body can cause adverse effects on immune function and induce several neurodegenerative disorders. So far, most of the reported fluorescent probes for Al3+ present some common drawbacks, such as low sensitivity and poor water solubility. In addition, a number of traditional fluorescent probes failed to image Al3+ in tumor cells due to the lack of tumor cell targeting capacity and cell penetrating abilities. To overcome these shortcomings, we constructed tumor-targeting fluorescent mixed nano-micelles (mPEG-Dye-Biotin) with an average particle size of 21 nm from an amphiphilic polymer containing a Schiff-base fluorescent unit (mPEG-Dye) and another amphiphilic polymer containing a tumor cell recognition ligand (DSPE-PEG-Biotin), through the co-self-assembly of both amphiphilic polymers in water using the film rehydration method. The as-prepared nanoprobe showed a highly sensitive and selective turn-on fluorescence response to Al3+ in aqueous solution with a low detection limit. MTT assay revealed the negligible cytotoxicity of the mPEG-Dye-Biotin nanoprobe to both HeLa cells and COS-7 cells, indicating the safety of mPEG-Dye-Biotin for biological applications. More importantly, the biotinylated nanoprobe showed better ability to enter biotin receptor-positive HeLa cells than that of the non-biotinylated micelle mPEG-Dye, which made it more suitable for imaging Al3+ in biotin receptor-positive tumor cells. This work provides a simple and general strategy to design a highly sensitive and tumor cell-specific metal ion nanoprobe, which can not only be applied in Al3+ imaging, but can also be extended to other ions or biomolecules by changing the incorporated fluorescent unit in the amphiphilic polymer.

Discovery of perturbation gene targets via free text metadata mining in Gene Expression Omnibus.

There exists over 2.5 million publicly available gene expression samples across 101,000 data series in NCBI's Gene Expression Omnibus (GEO) database. Due to the lack of the use of standardised ontology terms in GEO's free text metadata to annotate the experimental type and sample type, this database remains difficult to harness computationally without significant manual intervention. In this work, we present an interactive R/Shiny tool called GEOracle that utilises text mining and machine learning techniques to automatically identify perturbation experiments, group treatment and control samples and perform differential expression. We present applications of GEOracle to discover conserved signalling pathway target genes and identify an organ specific gene regulatory network. GEOracle is effective in discovering perturbation gene targets in GEO by harnessing its free text metadata. Its effectiveness and applicability has been demonstrated by cross validation and two real-life case studies. It opens up new avenues to unlock the gene regulatory information embedded inside large biological databases such as GEO. GEOracle is available at https://github.com/VCCRI/GEOracle.

East China Sea increasingly gains limiting nutrient P from South China Sea.

The Taiwan Strait (TS) directly connects two of the richest fishing grounds in the world - the East China Sea (ECS) and the South China Sea (SCS). Carbon and nutrient supplies are essential for primary production and the Yangtze River is an important source for the ECS. However the ECS is severely P-limited. The TS transports an order of magnitude more carbon and a factor of two more phosphate (P) to the ECS than the Yangtze River does. To evaluate the temporal variability of these supplies, the total alkalinity (TA), dissolved inorganic carbon (DIC), nitrate plus nitrite (N), P, and silicate (Si) fluxes through the TS were estimated using empirical equations for these parameters and the current velocity, which was estimated using the Hybrid Coordinate Ocean Model (HYCOM). These empirical equations were derived from in situ salinity and temperature and measured chemical concentrations that were collected during 57 cruises (1995-2014) with a total of 2096 bottle samples. The 24-month moving averages of water, carbon, and nutrient fluxes significantly increase with time, so does the satellite chlorophyll a concentration. More importantly, the increased supply of the badly needed P from the TS is more than that from the Yangtze River.