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Catalytic microsweepers with single-iron-atom centers were designed to search for and inhibit Helicobacter pylori using dynamically navigated reciprocating locomotion.

Genetically encoded molecular tools are crucial for live cell RNA imaging, and few are available for endogenous RNA imaging. We develop a new genetically encoded sensor using conformation switching RNA induced fluorogenic proteins that enable multicolor and signal-amplified imaging of endogenous RNAs. The sensor system is designed with an RNA sensing module and a degron-fused fluorescent protein reporter. Target RNA induces conformation switching of the RNA sensing module to form RNA aptamers that stabilize the degron-fused protein for fluorogenic imaging. This sensor is demonstrated for high-contrast imaging of survivin mRNA abundance and dynamics in live cells. Moreover, the sensor system is extended to a multicolor palette by screening fluorogenic proteins of distinct colors, and engineered into a signal amplifier using the split fluorescent protein design. The sensor is further exploited for imaging lncRNA MALAT-1 and its translocation dynamics during mitosis. Our sensor system can afford a valuable platform for RNA imaging in biomedical research and clinical theranostics.

Hydroxychloroquine (HCQ) is derivative of the heterocyclic aromatic compound quinoline, which has been used for the treatment of autoimmune diseases. The central purpose of this study was to investigate therapeutic effects and inflammatory immunological molecular mechanism of HCQ in experimental autoimmune hepatitis (AIH). Treatment with HCQ ameliorated hepatic pathologic damage, inflammatory infiltration, while promoted regulatory T cell (Treg) and down-regulated CD8+T cell differentiation in AIH mice induced by S-100 antigen. In vitro, HCQ also suppressed pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-12) secretion, promoted anti-inflammatory cytokine (TGF-β1) secretion. HCQ mainly impaired T cell lipid metabolism but not glycolysis to promote Treg differentiation and function. Mechanistically, HCQ down-regulated GRK2 membrane translocation in T cells, inhibited GRK2-PI3K interaction to reduce the PI3K recruiting to the membrane, followed by suppressing the phosphorylation of PI3K-AKT-mTOR signal. Pretreating T cells with paroxetine, a GRK2 inhibitor, disturbed HCQ effect to T cells. HCQ also reversed the activation of the PI3K-AKT axis by 740 Y-P (PI3K agonist). Meanwhile, HCQ inhibited the PI3K-AKT-mTOR, JAK2-STAT3-SOCS3 and increased the AMPK signals in the liver and T cells of AIH mice. In conclusion, HCQ exhibited specific and potent therapeutic effects on AIH and attendant liver injury, which was attributed to HCQ acted on GRK2 translocation, inhibited metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 signal in T lymphocytes, thereby modulating lipid metabolism of T cell function to regulate Treg differentiation and function.

Autism spectrum disorder (ASD), a highly hereditary and heterogeneous neurodevelopmental disorder, is influenced by genetic and environmental factors. Tuberous sclerosis complex (TSC) is a common syndrome associated with ASD. Cytomegalovirus (CMV) infection is an environmental risk factor for ASD. The similarities in pathological and mechanistic pathways of TSC and CMV intrigued us to investigate whether CMV and TSC interacted in ASD's occurrence. We detected CMV IgG seroprevalence of 308 TSC patients from our prospective cohort (September 2011 to March 2021) and 93 healthy children by magnetic particle indirect chemiluminescence immunoassay. A total of 206 TSC patients enrolled were divided into ASD and non-ASD groups, and the relationship between ASD and CMV seroprevalence was analyzed. Nested PCR and Western blot were used to detect CMV DNAs and proteins in cortical malformations of seven TSC patients with and without ASD. No difference was found in CMV seroprevalence between TSC patients and healthy children (74.0% versus 72.0%

To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency.The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function.The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family.The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.复合杂合突变导致的遗传性凝血因子Ⅻ缺陷症家系分析.对1个遗传性凝血因子Ⅻ（FⅫ）缺陷症家系进行临床表型及基因突变分析，探讨其分子致病机制.检测先证者及其家系成员（共3代5人）血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原含量（FIB）、D-D二聚体（D-D）、凝血因子Ⅻ促凝活性（FⅫ:C）和凝血因子Ⅻ抗原（FⅫ:Ag）等凝血指标。采用高通量测序方法分析先证者F12基因所有的外显子编码区及外显子-内含子交界处的基因突变情况，对检出的可疑致病突变进行Sanger测序验证，并对家系成员的相应突变位点进行检测。采用AutoPVS1和Mutation Taster在线生物信息学软件预测突变位点对蛋白功能的影响.先证者APTT结果为180.9 s，明显延长；FⅫ:C和FⅫ:Ag分别降低至0.8%和4.17%。全外显子组测序分析发现先证者F12基因存在复合杂合突变，即第11号外显子c.1261G＞T杂合无义突变（p.Glu421*）和第4号外显子c.251dupG杂合移码突变（p.Trp85Metfs*53），均为功能缺失型突变，属于极强致病性级别。Sanger测序家系验证结果显示，先证者c.1261G＞T杂合突变遗传自其母亲，其哥哥和女儿均为c.1261G＞T杂合突变携带者。在此家系中基因检测结果与血液学检查结果相符，即基因型和表型共分离.F12基因第11号外显子c.1261G＞T杂合无义突变和第4号外显子c.251dupG杂合移码突变是本例家系遗传性凝血因子Ⅻ缺陷症的分子发病机制，这两个突变均为国际上首次报道的新突变.

Herein, we develop a novel tripartite DNA probe to transport phosphorothioated substrate hairpins and an aptamer for the intramolecular CHA circuit, which achieves detection of a low amount of specific mRNA in living cells and mice. Our study provides an improved strategy to promote in vivo fluorescence imaging applications in early-stage clinical diagnosis.

Nicotinamide phosphoribosyltransferase (NAMPT) is a critical rate-limiting enzyme involved in NAD synthesis that has been shown to contribute to the progression of liver cancer. However, the potential role and mechanism of NAMPT in hepatitis B virus (HBV)-associated liver cancer remain unclear. The present study assessed the expression of NAMPT in HBV-positive and -negative liver cancer cells, and investigated whether HBV-induced NAMPT expression is dependent on HBV X protein (HBx). In addition, the role of NAMPT in HBV replication and transcription, and in HBV-mediated liver cancer cell growth was explored. The effects of NAMPT on the glycolytic pathway were also evaluated. Reverse transcription-quantitative PCR and western blotting results revealed that NAMPT expression levels were significantly higher in HBV-positive liver cancer cells than in HBV-negative liver cancer cells, and this effect was HBx-dependent. Moreover, the activation of NAMPT was demonstrated to be required for HBV replication and transcription. The NAMPT inhibitor FK866 repressed cell survival and promoted cell death in HBV-expressing liver cancer cells, and these effects were attenuated by nicotinamide mononucleotide. Furthermore, the inhibition of NAMPT was associated with decreased glucose uptake, decreased lactate production and decreased ATP levels in HBV-expressing liver cancer cells, indicating that NAMPT may promote the aerobic glycolysis. Collectively, these findings reveal a positive feedback loop in which HBV enhances NAMPT expression and the activation of NAMPT promotes HBV replication and HBV-mediated malignant cell growth in liver cancer. The present study highlights the important role of NAMPT in the regulation of aerobic glycolysis in HBV-mediated liver cancer, and suggests that NAMPT may be a promising treatment target for patients with HBV-associated liver cancer.

OBJECTIVE: To investigate the nutritional recovery status of children with moderate or severe malnutrition during hospitalization after discharge. METHODS: The children with moderate or severe malnutrition were given nutrition support during hospitalization. They received a regular follow-up and nutrition guidance after discharge. The weight-for-age and height-for-age Z-scores reaching above -2SD were considered the nutrition criterion for ending follow-up. RESULTS: Among the 298 children with moderate or severe malnutrition, 174 (58.4%) reached the criterion for ending follow-up, 100 (33.6%) were lost to follow-up, 18 (6.0%) died, and 6 (2.0%) did not reach the criterion for ending follow-up after 18 months of follow-up. The children with malnutrition in the department of surgery had a significantly higher proportion of children reaching the criterion for ending follow-up than those in the department of internal medicine (P < 0.05). The children with severe malnutrition had a significantly higher loss to follow-up rate than those with moderate nutrition (P < 0.05). The majority of children with emaciation reached the criterion for ending follow-up at month 3 after discharge, while those with growth retardation reached such the criterion at months 3-6 after discharge. Up to 1 year after discharge, more than 80% of the children with different types of malnutrition reached the nutrition criterion for ending follow-up. CONCLUSIONS: Most of the children with malnutrition who adhere to follow-up can reach the expected nutrition criterion within 1 year after discharge. The children with growth retardation have slower nutritional recovery than those with emaciation.

Nine antialgal active compounds, (i.e. trehalose (1), twenty-two methyl carbonate (2), (-)-dihydromenisdaurilide (3), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (4), isophytol (5), 8-hexadecenol (6), 17-hydroxyheptadecanoic acid (7), trans-asarone (8) and 2-amino-3-mercaptopropanoic acid (9)) were isolated from Ulva pertusa for the first time by sephadex LH-20 column chromatography, silica gel column chromatography and repeated preparative TLC. Except for compound 4, all compounds represented novel isolated molecules from marine macroalgae. Further, antialgal activities of these compounds against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense and Skeletonema costatum were investigated for the first time. Results showed these nine compounds have selectivity antialgal effects on all test red tide microalgae, and antialgal activities against red tide microalgae obviously enhanced with the increase of concentration of antialgal compounds. Based on this, EC50–96 h values of these nine compounds for six red tide microalgae were obtained for the first time. By analyzing and comparing EC50–96 h values, it has been determined that seven compounds (1, 3, 4, 6, 7, 8 and 9) showed the superior application potential than potassium dichromate or gossonorol and other six compounds as a characteristic antialgal agent against Heterosigma akashiwo, Karenia mikimitoi and Prorocentrum donghaiense. Overall this study has suggested that green algae Ulva pertusa is a new source of bioactive compounds with antialgal activity.

Objectives Abundant studies have suggested that TLR2 genetic variants involve in susceptibility to TB infection. We tried to verified the hypothesis that TLR2 genetic loci effect on the susceptibility to TB in the Western Chinese population. Methods A total 1109 individuals (634 TB patients and 475 healthy controls) were genotyped for rs3804099, rs3804100 and rs76112010 by using a custom-by-design 2x48-Plex SNP scan TM Kit. The statistical analysis between candidate 3 SNPs and risk and phenotypes of TB were conducted in this study. Significant SNPs were further interrogated in relation to TB susceptibility to TB infection and clinical phenotypes. Results None of the three genetic loci (rs3804099, rs3804100 and rs76112010) showed statistically significant differences between all TB cases and healthy controls in genotype, allele frequencies and genetic models (all p > 0.05). Statistical comparisons of retreatment TB cases and healthy controls or primary cases revealed that rs3804099 was significantly associated with the increased risk of developing TB in Western Chinese population. For genotypes frequencies, the subgroups of retreatment TB group versus healthy control group analysis and retreatment TB group versus primary TB group analysis results showed the p = 0.041 and p = 0.002 respectively. For recessive model, the subgroup of retreatment TB group versus healthy control group and retreatment TB group versus primary TB group analyses showed the p = 0.028 and P = 0.002 after Bonferroni correction respectively. Furthermore, analysis of the genotypes of rs76112010 in relation to clinical phenotypes of active TB using the dominant model demonstrated that it was strongly correlated with different hematological parameters (Erythrocyte P = 0.043, Hemoglobin P = 0.047, Hematocrit P = 0.027). Conclusion Our study presented the significant associations of rs3804099 with TB susceptibility in the retreatment TB subgroup analysis. Our study proposed that common TLR2 genetic variants may influence TB development and disease phenotypes in Western Chinese population.

Tandem mass spectrometry has been the principal method in shotgun proteomics for peptide and protein identification. However, incorrect identifications reported by proteome search engines are still unknown, and further validation methods are needed. We have proposed a validation method pValid before, but its scope of application is limited because two features used in pValid are related to open database search and sub-optimal peptide candidates for tandem mass spectra, and the performance on complex datasets still has room for improvement. In this study, we developed a more comprehensive validation method, pValid 2, to break these limitations by removing the two features and bringing in a new feature related to the retention time predicted by a deep learning-based method pPredRT. pValid 2 yielded an average false positive rate of 0.03% and an average false negative rate of 1.37% on three testing datasets, better than those of pValid, and flagged 8.47% to 11.31% more incorrect identifications than pValid on two complex datasets. Moreover, pValid 2 flagged almost all decoy identifications in validating the open-search datasets. In addition, the function of validating identifications given by MaxQuant and MS-GF+ was implemented in pValid 2, and the validation results showed that pValid 2 performed dramatically better than three metabolic labeling validation methods. Further considering its cost-effectiveness as a pure computational approach, pValid 2 has the potential to be a widely used validation tool for peptide identifications of any proteome search engines in shotgun proteomics. SIGNIFICANCE: Identification results given by shotgun proteomics are vital to life science research. The correctness of identifications deeply affects the precision of the subsequent studies about protein structures and functions, protein-protein interactions, pathogenic mechanism, and targeted drugs. Thus, validating the correctness of identifications is crucial and urgent. In 2019, we developed an identification credibility validation method named pValid, whose false positive rate (FPR) is 0.03% and false negative rate (FNR) is 1.79%, comparable to those of the gold standard, i.e., the Synthetic-peptide validation method. However, pValid can only be used for validating the results from pFind, and its validation performance on a few complex datasets still has room for improvement. So, in this submission, we proposed pValid 2, a more comprehensive computational validation method that can validate identifications from any proteome search engines with increased discriminating power.

OBJECTIVE In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD. METHODS We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files. RESULTS Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years. SIGNIFICANCE Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.

In the past decade, tandem mass spectrometry (MS/MS)-based bottom-up proteomics has become the method of choice for analyzing post-translational modifications (PTMs) in complex mixtures. The key to the identification of the PTM-containing peptides and localization of the PTM-modified residues is to measure the similarities between the theoretical spectra and the experimental ones. An accurate prediction of the theoretical MS/MS spectra of the modified peptides will improve the similarity measurement. Here, we proposed the deep-learning-based pDeep2 model for PTMs. We used the transfer learning technique to train pDeep2, facilitating the training with a limited scale of benchmark PTM data. Using the public synthetic PTM data sets, including the synthetic phosphopeptides and 21 synthetic PTMs from ProteomeTools, we showed that the model trained by transfer learning was accurate (>80% Pearson correlation coefficients were higher than 0.9), and was significantly better than the models trained without transfer learning. We also showed that accurate prediction of the fragment ion intensities of the PTM neutral loss, for example, the phosphoric acid loss (-98 Da) of the phosphopeptide, will improve the discriminating power to distinguish the true phosphorylated residue from its adjacent candidate sites. pDeep2 is available at https://github.com/pFindStudio/pDeep/tree/master/pDeep2 .

As the de facto validation method in mass spectrometry-based proteomics, the target-decoy approach determines a threshold to estimate the false discovery rate and then filters those identifications beyond the threshold. However, the incorrect identifications within the threshold are still unknown and further validation methods are needed. In this study, we characterized a framework of validation and investigated a number of common and novel validation methods. We first defined the accuracy of a validation method by its false-positive rate (FPR) and false-negative rate (FNR) and, further, proved that a validation method with lower FPR and FNR led to identifications with higher sensitivity and precision. Then we proposed a validation method named pValid that incorporated an open database search and a theoretical spectrum prediction strategy via a machine-learning technology. pValid was compared with four common validation methods as well as a synthetic peptide validation method. Tests on three benchmark data sets indicated that pValid had an FPR of 0.03% and an FNR of 1.79% on average, both superior to the other four common validation methods. Tests on a synthetic peptide data set also indicated that the FPR and FNR of pValid were better than those of the synthetic peptide validation method. Tests on a large-scale human proteome data set indicated that pValid successfully flagged the highest number of incorrect identifications among all five methods. Further considering its cost-effectiveness, pValid has the potential to be a feasible validation tool for peptide identification.

To screen the genes with significant changes in DNA methylation level in active tuberculosis patients, we used the methylation chips and expanded the sample size to verify candidate genes.① This study enrolled 9 cases of active tuberculosis patients, 3 cases of latent tuberculosis patients and 3 cases of healthy controls whose age and gender were all matched. Genome DNA was extracted from peripheral blood mononuclear cell in blood samples collected from these candidates, and bisulfite conversion treatment was then conducted. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, and GO and KEGG pathway analyses were performed to evaluate the function of differentially expressed genes. ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (age-and gender-matched), DNA was extracted from their peripheral blood and also followed bisulfite conversion treatment. Pyrosequencing method was used to detect the methylation levels of candidate genesCompared with healthy controls, the fragments in the patients that showed low methylation change accounted for the vast majority. Most of the methylation differential fragments (DMRs) were located in the main body region, followed by the upstream region of transcription initiation site, and the lowest DMRs distribution area was 3´UTR area. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes are mainly enriched in the biological processes of the regulation of leukocyte differentiation, apoptosis, cytokine regulation and inflammatory response which are closely related to tuberculosis. There were 32 CpG sites involved in the verified 7 tuberculosis related genes, and 16 CpG locus showed significant difference (In the course of MTB infection, the methylation status of genomic DNA is altered, and most of the differentially methylated regions (DMRs) are showed status of demethylation. The expressions of

BACKGROUND Antituberculosis drug-induced liver injury (ATDILI) is increasing globally and, hence, it is crucial to predict its risk in the clinical management of antituberculosis therapy. As a major antioxidant, superoxide dismutase (SOD) is mainly responsible for providing defence against oxidative stress, which is involved in ATDILI. The present study aimed to investigate the associations between polymorphisms in SOD genes, including Cu/ZnSOD (SOD1), mitochondrial manganese SOD (MnSOD or SOD2) and extracellular SOD (SOD3), as well as the susceptibility to ATDILI in a Chinese Han population. METHODS In total, 1060 Chinese Han subjects highly suspected to have tuberculosis (TB) were prospectively enrolled from West China Hospital of Sichuan University. Overall, 746 subjects comprising 118 ATDILI and 628 ATD-tolerant TB patients were eligible and were genotyped for seven single-nucleotide polymorphisms in three SOD genes (SOD1: rs4816407 and rs1041740; SOD2: rs4880; SOD3: rs699473, rs2536512, rs2855262 and rs8192290). RESULTS Logistic regression analysis showed that none of the seven genetic variants in the three SOD genes were significantly associated with susceptibility to ATDILI in the Chinese Han population after Bonferroni correction, except for a potential association for the SOD2 rs4880 A>G (G allele, p = 0.190, odds ratio = 1.53, 95% confidence interval = 1.05-2.23; GG genotype, p = 0.155). CONCLUSIONS The promising application of single-nucleotide polymorphisms in the SOD1, SOD2 and SOD3 genes as genetic markers for ATDILI is challenged, and further studies are needed with larger sample sizes and different ethnicities, especially for SOD2 rs4880.

Inadequate endometrial receptivity may be responsible for the low implantation rate of transferred embryos in in vitro fertilization (IVF) treatments. Patients with repeated implantation failure (RIF) impact the clinical pregnancy rate for IVF. We collected endometrial tissue during the implantation window of hysteroscopy biopsies from September 2016 to December 2019 and clinical data were collected simultaneously. Patients were divided into RIF and pregnant controls group according to pregnancy outcomes. A total of 82 differentially expressed endometrial proteins were identified, including 55 up-regulated proteins (>1.50-fold, P P

Two Zn MOFs {[Zn4(OH)(tipe)2(btc)2]·(OH)·9H2O·DMF}n (1·(OH)·9H2O·DMF) and {[Zn(tipe)1/2(bpdc)]·H2O}n (2·H2O) (tipe = 1,1,2,2-tetrakis(imidazol-1-yl)phenyl)ethylene, btc = 1,3,5-benezenetricarboxylate, bpdc = 2,2′-biphenyldicarboxylate) were obtained using the hydrothermal method and characterized. MOF 1 exhibits the (3,4,4,6)-connected 3D topology with point symbol of (83)(44·82)(4·84·12)(42·89·102·122). MOF 2 shows the (4,4)-connected 3D topology with point symbol of (84·102)2(42·82·102). MOF 1 and 2 present the strong luminescence emission at 507 nm and 492 nm, respectively. The energy gap ( E g), valence band (Ev) and conduction band (Ec) data of MOF 1 and 2 were 2.31 and 2.17 eV, 2.37 and 2.54 eV, 0.06 and 0.37 eV, respectively. MOF 1 and 2 are good photocatalytic and sonocatalytic catalysts for degradation of methylene blue under visible light and ultrasound irradiation. The catalytic mechanism was proposed.

Background: Over the past several decades, hundreds of genetic studies have been conducted to investigate associations between variants and risk of tuberculosis. But results have been inconclusive and no comprehensive quantitative synopsis has been available. We aimed to provide a summary of the current understanding of the genetic architecture of tuberculosis susceptibility. Methods: We systematically searched PubMed, Embase and Web of Science to identify genetic association studies of tuberculosis published through October 16, 2018. We did a meta-analysis for genetic variants with at least three independent datasets. We graded levels of cumulative epidemiological evidence of significant associations with risk of tuberculosis using the guidelines proposed by the Human Genome Epidemiology Network and false-positive report probability tests. We performed functional annotations for these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project and other databases. Findings: We identified 592 eligible articles comprising 250431 cases with tuberculosis and 698635 controls without this disease through screening a total of 21330 citations. Meta-analysis-analyses were done for 580 variants in 314 genes or loci. We found that 37 variants were nominally significantly associated with risk of tuberculosis. Cumulative epidemiological evidence for a significant association with risk of tuberculosis was graded strong for 12 variants in or near 12 genes. Data from the ENCODE and other databases suggested that 10 of the 12 variants with strong evidence and those correlated with them might fall within putative functional regions. These variants together explained approximately 15.82% of familial relative risk of tuberculosis. Interpretation: Our study summarizes current literature on the genetic architecture of tuberculosis susceptibility and provides useful data for designing future studies to investigate new genetic factors for risk of tuberculosis. Funding Statement: This research is supported by grants from National Natural Science Foundation of China 81472026, 81672095, 81702288, 81673255, 81874283, the Projects of the Health and family planning commission in Sichuan Province 16ZD004, China Postdoctoral Science Foundation Project 2018M643495, the Recruitment Program for Young Professionals of China, Army Medical University WX2015-013, Army Medical University First Affiliated Hospital SWH2015LC03, SWH2016ZDCX1012, SWH2016JQFY-02, and SWH2015QN11, Chongqing Special Postdoctoral Science Foundation XmT2018068. Declaration of Interests: The authors declared no conflicts of interest. Ethics Approval Statement: We conducted this study in accordance with the guidelines of the Human Genome Epidemiology Network (HuGENet) for systematic review of genetic association studies and the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement.

AIM Although peripheral low-grade inflammation and brain-derived neurotrophic factor (BDNF) levels have been implicated in schizophrenia (SCZ), the interactions between them remain to be fully revealed. We aimed to compare BDNF and cytokines in patients with SCZ and healthy controls (HC). Additionally, we aimed to investigate the association between peripheral levels of cytokines and BDNF in patients with SCZ. METHODS Plasma levels of BDNF, interferon gamma, interleukin (IL)-10, IL-12, IL-1, IL-6, IL-8, tumor necrosis factor alpha, macrophage migration inhibitory factor, IL-1 receptor antagonist (IL-1Ra), and CD40 Ligand were compared in 45 SCZ patients and 38 HC using Luminex technology. RESULTS Compared to HC, patients had significantly higher IL-1Ra levels (P = 0.031). We found a strong positive association between BDNF and CD40 Ligand in the patient group (rho = 0.858, P < 0.001) as well as in the HC group (rho = 0.822, P < 0.001), respectively. Furthermore, there was a negative association between BDNF and tumor necrosis factor alpha in patients (rho = -0.429, P = 0.030) as well as in HC (rho = -0.649, P < 0.001). CONCLUSION These results suggest that the cytokine IL-1Ra may play a role in SCZ pathophysiology. Additionally, the interaction between cytokines and BDNF levels further indicated the diverse actions of these cytokines.

Lipase (EC 3.1.1.3) stands amongst the most important and promising biocatalysts for industrial applications. In this study, in order to realize a high-level expression of the Yarrowia lipolytica lipase gene in Pichia pastoris, we optimized the codon of LIP2 by de novo gene design and synthesis, which significantly improved the lipase expression when compared to the native lip2 gene. We also comparatively analyzed the effects of the promoter types (PAOX1 and PFLD1) and the Pichia expression systems, including the newly developed PichiaPink system, on lipase production and obtained the optimal recombinants. Bench-top scale fermentation studies indicated that the recombinant carrying the codon-optimized lipase gene syn-lip under the control of promoter PAOX1 has a significantly higher lipase production capacity in the fermenter than other types of recombinants. After undergoing methanol inducible expression for 96h, the wet cell weight of Pichia, the lipase activity and the protein content in the fermentation broth reached their highest values of 262g/L, 38,500U/mL and 2.82g/L, respectively. This study has not only greatly facilitated the bioapplication of lipase in industrial fields but the strategies utilized, such as de novo gene design and synthesis, the comparative analysis among promoters and different generations of Pichia expression systems will also be useful as references for future work in this field.

We present a sequence-tag-based search engine, Open-pFind, to identify peptides in an ultra-large search space that includes coeluting peptides, unexpected modifications and digestions. Our method detects peptides with higher precision and speed than seven other search engines. Open-pFind identified 70-85% of the tandem mass spectra in four large-scale datasets and 14,064 proteins, each supported by at least two protein-unique peptides, in a human proteome dataset.

To investigate the molecular features of spinal muscular atrophy (SMA) related genes in SMA patients of Han nationality of southwest of China.We collected 62 unrelated patients of SMA and 50 unrelated healthy individuals in this study.The copy numbers of survival motor neuron gene (Of 62 patients,the copy number of SMA1-4 were 30.65% (19/62),41.94%(26/62),16.13% (10/62),11.29% (7/62),respectively.The deletion of SMN1 exon 7 accounts for 98.38% (61/62).The deletion ofThe deletion of

To determine the correlation between gene polymorphisms in Wnt signal pathway and susceptibility of Chinese Tibetan people to tuberculosis.A total of 488 active tuberculosis patients and 454 healthy subjects(control) were enrolled in this case-control study.Five single nucleotide polymorphisms (SNPs) in Wnt signal pathway (rs4135385 inThe genotype distributions of all SNPs coincided with the Hardy-Weinberg equilibrium in the 2 groups.The frequencies of genotype and allele of rs7832767 in

Background The development of pharmacogenomics has created an urgent need for robust molecular characterization. And it has become a challenge to develop suitable detecting methods for routine clinical use. Aim The aim of the current study is to develop a simple and reliable TYMS 1494del6 polymorphism genotyping assay by duplex scorpion primers in the Chinese Han population. Method We evaluated the performance of the duplex scorpion primer assay in the genotyping of TYMS 1494del6 polymorphism and screened 54 DNA samples of the Chinese Han population. The results were further validated by pyrosequencing. Results The duplex scorpion primer assay showed high specificity and accuracy for genotyping TYMS 1494del6 polymorphism. Complete concordance was observed between the duplex scorpion primer assay and pyrosequencing. The frequency of the TYMS + 6 bp allele was 34% and the − 6 bp allele was 66% in 54 Chinese Han population DNA samples. Conclusion The duplex scorpion primer assay provides a rapid, reliable and high-throughput method to genotype TYMS 1494del6 polymorphism in the Chinese Han population.

Rheological and interfacial property of nanoAl with Hydroxyl-terminated polybutadiene (HTPB), glycidyl azide polymer (GAP) and poly (ethyleneoxide-co-tetrafuran)(PET) were investigated by means of RS-300 rheometer, DCAT21 dynamic contact angle measuring instrument, interface surface tension meter (Germany) and X-ray photoelectron spectroscopy (xps). Rheological properties of three binders and nanoAl/binder suspensions in the mixing ratio of 1:2 were discussed. Results show that Three kinds of binders exhibit pseudoplastic characteristics with the apparent viscosity of less than 3 Pa s,and have weak interaction between molecular chain segment of itself. Within 30~60°C, with temperature increasing, the apparent viscosity of nanoAl suspensions decreases, in which the nanoAl/HTPB and nanoAl/GAP belong to pseudoplastic fluid of sensitive to temperature, with flow activation energy of 38.05 kJ/mol and 52.07 kJ /mol, respectively, but nanoAl/PET belongs to a bingham fluid of sensitive to changes in the shear rate, with flow activation energy of only 1.506 kJ/mol. The contact angles of nanoAl,GAP,HTPB and PET were measured by means of dynamic contact angle/surface tension instrument. The calculated values of adhesion and spread coefficient of nanoAl with binders decrease in the order Wnano-Al/PET>Wnano-Al/GAP>Wnano-Al/HTPB and Snano-Al/PET>Snano-Al/GAP>Snano-Al/HTPB.The results indicate that the interactions of nanoAl with binders decrease in the order nanoAl/PET>nanoAl/GAP>nanoAl/HTPB,which is consistent with the trends of apparent viscosity of the suspensions . Binding energy of Oxygen in nanoAl/HTPB is 532.03 ev,which is bigger than that of nanoAl,and indicate a strong action between nanoAl and HTPB.

Sun, Y.; Dong, S.; Zhou, W.; Guo, L.; Guo, G., and Zhang, X., 2019. A comprehensive review of secondary metabolites with antialgal activity from marine macroalgae against red tide microalgae. In: Guido-Aldana, P.A. and Mulahasan, S. (eds.), Advances in Water Resources and Exploration. Journal of Coastal Research, Special Issue No. 93, pp. 475–488. Coconut Creek (Florida), ISSN 0749-0208.Red tide, mainly caused by the large-scale reproduction of microscopic algae, has virtually affected every coastal country or region in the whole world over the last several decades. In order to control and mitigate the proliferation and diffusion of red tide microalgae, there are many methods or strategies for fighting or inhibiting red tide microalgae species, these methods or strategies included mechanical, chemical, biological, genetic methods and others. Unfortunately, the use of these methods or strategies is usually ineffective. There are some evidences that the inhibition effect of marine macroalgae on the growth of red tide microalgae is mainly due to the release of bioactive molecules, which are mainly secondary metabolites. Thus, antialgal secondary metabolites, isolated marine macroalgae, have become an environmentally friendly alternative approach. And relevant researches of antialgal secondary metabolites in marine macroalgae, such as screen, isolation, identification and other research etc., have also become very important subjects to biological control of red tide microalgae. The inhibition effects of marine macroalgae on red tide microalgae are here reviewed, focusing on antialgal secondary metabolites, isolated from marine macroalgae, against red tide microalgae growth. Further, this paper describes isolation and EC50-96 h (half maximal effective concentration) or IC50-96 h (half maximal inhibitory concentration) for red tide microalgae of some antialgal secondary metabolites, including the recently discovered compounds. Finally, this review is the first to demonstrate that development relationships between macroalgae and red tide using CiteSpace, and cluster view of macroalgae and red tide is given for the first time. This work provides scientists in the field with the necessary information and the urgent need to isolate and identify screening antialgal secondary metabolites in different marine macroalgae. Also, analysis result, which obtained through CiteSpace, has pointed out that allelopathic interaction between marine macroalgae and red tide microalgae has been developed into a study area during the last twenty years.

In this paper, the forming process is applied to the structure design of the metal bellows for the synergistic optimization.With bellows minimum overall stiffness and minimum weight for the optimization objectives to establish multi-objective optimization design model, using the Maximin fitness function strategy based multi-objective particle swarm optimization algorithm and introduce the multiple subgroup cooperative search strategy by master-slave clustering to get the optimized solution at the same time. The algorithm is applied to the synergistic optimization of the metal bellows structure design. The results show that the convergent speed of the algorithm is fast and can effectively approximate the actual bellows structure design, and provide users with more practical and intuitive effectively design scheme.

Previous studies showed that methanol extracts from Porphyra yezoensis significantly inhibited Karenia mikimitoi and Skeletonema costatum. Five sesquiterpenoids (1–5) were successfully isolated from this marine macroalga through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography in this paper. Their structure was identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), cyclonerodiol (3), cadinol, (4) and 4-cadinen-1-ol (5) on the basis of spectroscopic data. These sesquiterpenoids were isolated from Porphyra yezoensis for the first time, and cyclonerodiol (3) and cadinol (4) isolated from marine macroalgae for the first time. Further, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal sesquiterpenoid (gossonorol, 7,10-epoxy-ar-bisabol-11-ol and cyclonerodiol) was determined and important parameters, e.g., EC50-96h for future practical HAB control are to be obtained. Results showed that three sesquiterpenoids (1–3) had selective antialgal activity against the growth of red tide microalgae (Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense, and Skeletonema costatum). More than two test red tide microalgae were significantly inhibited by these three sesquiterpenoids (1–3). Their antialgal activity against red tide microalgae has not been previously reported. Furthermore, EC50-96h of gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) for specific test red microalgae were not only significantly less than 10 μg/mL, but also were smaller than/or very close to those of potassium dichromate. Gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) possessed good application potential than potassium dichromate as a characteristic antialgal agent against the specific harmful red tide microalgae (Heterosigma akashiwo, Phaeocystis globosa, and Prorocentrum donghaiense) (or Heterosigma akashiwo and Karenia mikimitoi).

Anaerobic digestion is a widely applied technology to produce biogas from organic wastewater. The biogas calorific value depends on the methane-content. For biogas flows >100 m3/h, the two-step process is usually used for production of high calorific biogas from organic wastewater: the first step, anaerobic digestion; the second step, biogas purification. However, for biogas flows 3/h, biogas purification is not economical, and one-step process according to the big gap between methane and non-methane-gas in solubility at higher pressure or lower temperature, should be condidered. New anaerobic digestion processes, such as micro-aerobic process, electrolysis enhancing methane production process, process of internal circulation anaerobic digester (ICAD) with sewage source heat pump, may all enhance biogas producton or lower biogas production cost. In addition, suitable environmental conditions, such as organic loading rate (OLR), solid retention time (SRT), hydraulic retention time (HRT) and surface area, are all beneficial to enhance methane fermentation. Furthermore, new operation modes and optimal dose of trace metals might be selected.

BACKGROUND AND PURPOSE Besides targeting the well-known oncogenic c-Met, crizotinib is the first oral tyrosine kinase inhibitor inhibiting anaplastic lymphoma kinase (ALK) in clinical trials for the treatment of non-small cell lung cancer. Here, we assessed the possible reversal of multidrug resistance (MDR) by crizotinib in vitro and in vivo. EXPERIMENTAL APPROACH 1-(4,5-Dimethylthiazol-2-yl)-3,5- diphenylformazan was used in vitro and xenografts in nude mice were used in vivo to investigate reversal of MDR by crizotinib. To understand the mechanisms for MDR reversal, the alterations of intracellular doxorubicin or rhodamine 123 accumulation, doxorubicin efflux, ABCB1 expression level, ATPase activity of ABCB1 and crizotinib-induced c-Met, Akt and ERK1/2 phosphorylation were examined. KEY RESULTS Crizotinib significantly enhanced the cytotoxicity of chemotherapeutic agents which are also ABCB1 substrates, in MDR cells with no effect found on sensitive cells in vitro and in vivo. Additionally, crizotinib significantly increased intracellular accumulation of rhodamine 123 and doxorubicin and inhibited the drug efflux in ABCB1-overexpressing MDR cells. Further studies showed that crizotinib enhanced the ATPase activity of ABCB1 in a concentration-dependent manner. However, expression of ABCB1 was not affected, and reversal of MDR by crizotinib was not related to the phosphorylation of c-Met, Akt or ERK1/2. Importantly, crizotinib significantly enhanced the effect of paclitaxel against KBv200 cell xenografts in nude mice. CONCLUSIONS AND IMPLICATIONS Crizotinib reversed ABCB1-mediated MDR by inhibiting ABCB1 transport function without affecting ABCB1 expression or blocking the Akt or ERK1/2 pathways. These findings are useful for planning combination chemotherapy of crizotinib with conventional chemotherapeutic drugs.

Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine upregulated in acute phase of heart ischemic disease. Controversial effects of IL-1β have been demonstrated on endothelial progenitor cells (EPCs) functional activity. The aim of this study was to investigate the in vitro effect of IL-1β on activity of human origin EPCs and the possible mechanism involved. EPCs were isolated from peripheral blood of healthy volunteers without cardiovascular risk factors and characterized. After ex vivo cultivation, EPCs were stimulated with a series of final concentrations (0, 0.1, 1, and 10 ng/ml) of IL-1β for 24 h. In some other experiments, EPCs were pretreated with 10 μM LY294002 (Akt inhibitor) for 30 min and then stimulated with 1 ng/ml IL-1β for 24 h. Cell proliferation, apoptosis, adhesion, and migration were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V/propidium iodide binding assay, adhesion assay, and transwell migration assay. In addition, the vascular endothelial vascular growth factor-A (VEGF-A) production has been examined using quantitative real-time RT-PCR and ELISA assay. Furthermore, the total and phosphorylation level of Akt was determined by Western blot. IL-1β significantly stimulated EPC proliferation, migration, and adhesion and upregulated the angiogenic growth factor VEGF-A at mRNA and protein level, while exerted no influence on cell apoptosis. However, pretreatment with LY294002 significantly diminished IL-1β-induced proliferation, migration, adhesion, and VEGF-A production. One nanogram per milliliter IL-1β for 15 min activated phosphorylation of Akt. These results suggest a potent role for IL-1β in upregulating EPCs functions. The phosphatidyl-inositol-3-kinase-Akt signaling pathway could be involved in the regulation of EPCs functions induced by IL-1β.

Organic photovoltaic(OPV) cells are rapidly gaining attention due to their potential to be fabricated at low cost in thin, flexible, and light-weight forms. For efficient generation of photo-induced charges,C60 has been indispensable electron acceptors in building heterojunctions with various suitable electron donors, such as CuPc, and Alq3 was always used as a new buffer layer to improve the degradation of heterojunction conductivity upon oxygen permeation In this work, the photoelectric properties of organic solar cells(ITO/CuPc/C60/ Al) were studied with a focus on the effect of substrate temperature. All the organic layers and the aluminum cathode were prepared onto ITO substrates by vacuum deposition at various substrate temperatures from room temperature to 363°CK. With increasing the substrate temperature , an improvement in crystallization of bilayer films(CuPc/C60) was observed by AFM. The results showed the photoconduction of the bilayer films increased because the bilayr films were well oriented, and the carrier mobility of the films were enhanced withby the increase of the substrate temperature.

A taper-shaped phosphonic acid, 3,4,5-tris(dodecyloxy)phenylmethylphosphonic acid (1), was synthesized; its lyotropic liquid crystalline (LLC) behaviour and its ability simultaneously to order and acid-dope polyaniline were examined. It was found that the ability of 1 to form LLC phases in the presence of several hydrophilic solvents is restricted by strong intermolecular interactions between the phosphonic acid head groups (presumably H-bonding). The amphiphile exhibits poor miscibility with pure water and even with strong H-bonding organic solvents such as DMF. However, it forms a lamellar mesophase in the presence of aqueous acid. Upon deprotonation of the phosphonic acid head group with NaOH, the resulting disodium salt of the amphiphile is able to form a well defined lamellar phase with pure water. The propensity of 1 to form lamellar phases is somewhat unusual since its tapered molecular shape should direct it to form an inverted hexagonal LLC phase. These results suggest that intermolecular head gr...

Tanshinone IIA is one of the major diterpenes from Salvia miltiorrhiza Bunge and has been shown to possess a protective effect on the endothelial cells. The present study aimed to investigate whether tanshinone IIA could protect against methylglyoxal (MGO)-induced injury in human brain microvascular endothelial cells (HBMEC). Using cultured HBMEC, cell viability was measured by MTT assay and trypan blue dye exclusion test. Cellular oxidative stress was measured by production of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and H2O2. AnnexinV/PI staining and western blot were performed to determine cell apoptosis and protein expression. We found that MGO treatment caused a concentration and time-dependent decrease in cell viability, which was inhibited by pretreatment with tanshinone IIA. Exposure to MGO promoted the accumulation of AGEs, and production of ROS, TBARS and H2O2 in the cultured HBMEC, which were inhibited by tanshinone IIA pretreatment. Addition of tanshinone IIA significantly reduced MGO-induced cell apoptosis as shown by flow cytometry. On the molecular level, tanshinone IIA administration altered the expression of apoptosis-related proteins such as p53, Bax, Bcl-2 and cyto C. In addition, MGO treatment remarkably increased the phosphorylation of MAPK family including p38, JNK and ERK. By contrast, addition of tanshinone IIA inhibited the activation of MAPK family members. These data indicated that tanshinone IIA could protect against MGO-induced cell injury through inhibiting MAPK activation in HBMEC.

Sturge–Weber syndrome (SWS) is a rare syndrome characterized by capillary‐venous malformations involving skin and brain. Many patients with SWS also suffer from drug‐resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients' age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well preserved, which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for focal cortical dysplasia (FCD). Neuropathology revealed dysmorphic‐like neurons with hypertrophic cell bodies reminiscent to those described for FCD type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD type IIa were missing, and we propose to classify this pattern as FCD ILAE type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n = 4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow‐up period of 1.7 years. We concluded from our study that FCD type IIIc and PMG are frequently associated findings in SWS. FCD type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control.

The development of functional materials with nanometer-scale architectures and the effect of these architectures on their chemical and physical properties are currently of great interest in materials design. Polymerizable lyotropic liquid crystal (LLC) assemblies provide a facile entry into this area by allowing one to fix the inherent order in these systems using covalent bonds to create robust, nanostructured materials. The use of the cross-linked inverted hexagonal phase in templated nanocomposite formation and heterogeneous catalysis has been demonstrated. Additionally, the polymerization of LLC mesogens in the regular hexagonal and bicontinuous cubic phases is being targeted for future developments in functional materials. Future directions for new applications of these materials are also discussed.

A simple method for the synthesis of pH-responding polymers containing barbituric acid moieties is described. The synthesis involves N-methyl-N′-(4-vinylbenzyl) urea (2) preparation and its polymerization in DMF using AIBN as the initiator to give poly(N-methyl-N′-(4-vinylbenzyl)urea) (4) with a number average molecular weight of 4.9×105 as determined by GPC. Cyclocondensation of urea with malonic acid in acetic acid/acetic anhydride affords the polymer (5) with pendant barbituric moieties. The pH-responding behavior of polymer 5 in water indicates that it has excellent pH-sensitivity at pH 6∼7. The potential and the versatility of this work are exciting and include the potential preparation of water-soluble polymers by modification of polyureas, metal chelating materials, and “smart” hydrogels upon crosslinking.

A simple and efficient method for the synthesis of lactose-based homopolymers from N-lactosyl-N‘-(4-vinylbenzyl)urea or N‘-lactosyl-N,N-methyl(4-vinylbenzyl)urea (5a, 5b) is described. Free radical...

An improved, simple, and efficient method for the synthesis of lactose-containing monomer acrylamidolactamine (LAM) has been reported. Free radical copolymerization of this monomer with N-isopropylacrylamide (NIPAM) in the presence of the crosslinking reagent N,N′-methylenebisacrylamide (BisA) (1.2 mol %) proceeded smoothly in an aqueous solution using potassium persulfate (KPS) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) as the initiating system and gave transparent hydrogels. Reactivity ratios were estimated from copolymerization reactions carried out in solution without BisA crosslinker and at low conversion, by using both linearization and nonlinearization methods. They were found to be rLAM = 0.75 and rNIPAM = 1.22. The swelling behavior of the hydrogels was studied by immersion of the hydrogels in deionized water at different temperatures. Equilibrium water uptake was increased when the LAM content was higher than 47 mol %, and reached ≈ 44-fold with 100 mol % LAM at room temperature. Depending on the composition, the gels showed sharp swelling transitions with small changes in temperature. Differential scanning calorimetry (DSC) was used to characterize the swelling transition and the organization of water in the copolymer hydrogels. The amounts of freezable water in these hydrogels ranged from 81 to 89%, and was not correlated to the content of the sugar monomer. These gels have potential applications as biocompatible materials. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1393–1402, 1999

D-Lactose-O-(vinylbenzyl)oxime (LVO), prepared from α-D-lactose and [O-(vinylbenzyl)oxy]amine (1) was copolymerized with styrene (ST) in dimethylsulfoxide (DMSO)-toluene (1 : 1, v/v) at 65°C using 2,2′-azobisisobutyronitrile (AIBN) as a free radical initiator. The polymerization was rapid when using AIBN as the initiator. The resultant copolymers were characterized by elemental analyses, infrared, viscometry, TGA, DSC, and 1H-NMR spectroscopy. The poly(ST-co-LVO) had an intrinsic viscosity in the range of 0.11–0.51 dL/g in DMSO at 30°C. The molecular weight was determined by gel permeation chromatography (GPC), and the molecular weight of the resulting polymers ranged from 2.11 × 104 to 6.53 × 107 with low polydispersities. The solubility of the copolymers with different monomer compositions in solvents of varied polarities was also studied. Incorporation of up to 65% (mol %) of lactose-based monomer onto polystyrene backbone led to a water-soluble polymer. Thermal behavior of the synthesized copolymers was evaluated by thermogravimetric analysis (TGA) and correlated very well with the polymer composition. Introduction of a pendant disaccharide compromised the thermal stability of the copolymer. The synthetic approach described in this report provides a route to prepare a novel disaccharide surfactant polymer with well-defined structures and hydrophilic/hydrophobic balances, by adjusting feed ratio of the lactose-based monomer (1) to styrene. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2971–2978, 1998

Copolymerization of d -lactose-O-(p-vinylbenzyl)-hydroxime (LVH), a new vinyl monomer, with acrylonitrile (AN) was performed in DMSO with AIBN as the initiator. The conversion of LVH is much faster than that of AN and reaches 100% in 2 h. The reactivity ratios of LVH and AN, as determined by the extended Kelen-Tudos method, are 1.0975 and 0.0554, respectively. Increasing the proportion of LVH in the monomer mixture significantly increases the LVH content in the copolymer. The conversion of monomers and the AN content in the copolymer rise gradually with increasing reaction time and initiator concentration. The number average molecular weights of the copolymers are independent of the monomer feed ratios. The LVH-co-AN copolymers exhibit lower glass transition temperatures than PLVH homopolymer. The presence of small amounts of LVH in the copolymer chain reduce the cyclization of nitrile groups in AN segments of the copolymer. Complete disappearance of nitrile cyclization is observed when the contents of LVH reaches and exceeds 16.9%.

α,ω-Bis-4(vinylbenzyl) ethers of mono-, di-, tetra-, and hexa(ethylene glycol) were used as cross-linkers in polystyrene beads to examine the influence of glycol tether length and % incorporation upon polymer swelling and reagent diffusion. Swelling of 2, 10, and 20% cross-linked poly{styrene-co-[oligo(ethylene glycol) bis(4-vinylbenzyl)ether]} (PS−PEG) beads was determined to be higher or comparable to 2% cross-linked poly[styrene-co-divinylbenzene] (2% PS−DVB) beads. Fluorescence quenching of polymer-bound dansyl groups by Et3O·BF4 indicated that the most rapid intraresin diffusion of this electrophilic reagent occurred in toluene. PS−PEG beads exhibited faster quenching than 2% PS−DVB in poor swelling solvents but were slower to quench than 2% PS−DVB in toluene.