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The in-situ nitrification process continuously requires a stable supply of oxygen. However, the application of conventional oxygen-releasing materials is limited by its high alkalinity and rapid oxygen release rates. In this study, a novel sulfur-based slow-release oxygen material (SOSM) was designed to address these challenges. SOSM releases oxygen through the decomposition of CaO 2 and maintains pH balance with sulfur (S 0 ). An 88-day continuous flow experiment for microbial degradation of ammonia nitrogen (NH 4 -N) was conducted with SOSM as a carrier. The results showed that the dissolved oxygen (DO) remained above 8 mg/L during 15 d, with oxygen being released following Fickian diffusion. S + -N) was conducted with SOSM as a carrier. The results showed that the dissolved oxygen (DO) remained above 8 mg/L during 15 d, with oxygen being released following Fickian diffusion. S 0 is oxidized by sulfur bacteria, forming a CaSO 4 precipitate within the material, while hydrogen ions (H + ) are generated to counteract the alkalinity caused by CaO 2 -N removal efficiency: the domestication phase (1-21 d, 86.2%), the stabilization phase (22-76 d, 93.4%), and the deterioration phase (77-88 d, 60.5%). The enrichment of Proteobacteria and Actinobacterota promoted NH 4 + -N removal efficiency: the domestication phase (1-21 d, 86.2%), the stabilization phase (22-76 d, 93.4%), and the deterioration phase (77-88 d, 60.5%). The enrichment of Proteobacteria and Actinobacterota promoted NH 4 + -N removal when oxygen was abundant, while the enrichment of Acidobacteriota facilitated active sulfur cycling. The system was dominated by nitrification and supplemented by the complete autotrophic nitrifying anaerobic ammonia oxidation (CANON) process. The SOSM developed in this study can effectively address the critical issues of in-situ agricultural drainage remediation and expand the application scope of nitrification technology. It offers a novel approach to biological nitrogen removal treatment technology, especially nitrification technology to remove NH 4 + ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by the progressive accumulation of globotriaosylceramide (Gb3) leading to systemic manifestations such as chronic kidney disease, cardiomyopathy, and stroke. There is still a need for novel markers for improved FD screening and prognosis. Moreover, the pathological mechanisms in FD, which also include systemic inflammation and fibrosis, are not yet fully understood., Methods: Plasma and platelets were obtained from 11 ERT (enzyme-replacement therapy)-treated symptomatic, 4 asymptomatic FD patients, and 13 healthy participants. A comprehensive targeted lipidomics analysis was conducted quantitating more than 550 lipid species., Results: Sphingadiene (18:2;O2)-containing sphingolipid species, including Gb3 and galabiosylceramide (Ga2), were significantly increased in FD patients. Plasma levels of lyso-dihexosylceramides, sphingoid base 1-phosphates (S1P), and GM3 ganglioside were also altered in FD patients, as well as specific plasma ceramide ratios used in cardiovascular disease risk prediction. Gb3 did not increase in patients' platelets but displayed a high inter-individual variability in patients and healthy participants. Platelets accumulated, however, lyso-Gb3, acylcarnitines, C16:0-sphingolipids, and S1P., Conclusions: This study identified lipidome changes in plasma and platelets from FD patients, a possible involvement of platelets in FD, and potential new markers for screening and monitoring of this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Currently, antibiotics and heavy metal contaminants have posed a great threat for ecological security and human health. Herein, the lanthanide functionalized ZIF (named ZIF-90-PABA-Eu) is constructed by coordinating with Eu 3+ via p-aminobenzoic acid intermediate. Due to the excellent fluorescence properties, the novel fluorescent probe can selectively monitor flumequine based on "turn on" mode. Furthermore, the obtained new material (named ZIF-90-PABA-Eu-Flu) can be used as "turn off" sensor for selective detection of both radioactive and nonradioactive heavy metal ions (UO 2 2+ , Ni 2+ and Cu 2+ ) which are the main component of nuclear industrial wastewater. ZIF-90-PABA-Eu-Flu shows ultra-short fluorescence response time (3 s) and ultra-low limit of detection (9.0 × 10 -3 , 1.3 × 10 -2 and 6.1 × 10 -4 ppm) for three metal ions, which may be attributed to its good affinity with UO 2 2+ , Ni 2+ and Cu 2+ . Moreover, principal component analysis (PCA) is applied to distinguish the three metal ions. Additionally, the possible sensing mechanism is investigated by the UV-vis spectra, luminescence lifetimes and theoretical calculation analysis. Based on these results, ZIF-90-PABA-Eu possesses promising potential in practical application and provides insight for the design of novel probes to continuously monitor flumequine, radioactive and nonradioactive heavy metal ions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor., Materials and Methods: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile., Results: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence., Conclusion: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

The development of multifunctional Mg-based active implants with controllable degradation and antibacterial capabilities has become a hotspot in the research field of biodegradable metallic materials. To this end, a BN nanosheets (BNNS) _vancomycin (Van) @chitosan (CS) nanocomposite coating containing two antibacterial components (BNNS and Van) was prepared on Mg alloys via a micro-arc oxidation (MAO) pre-treatment combined with following electrodeposition. The related characterizations of the coating show that the composite coating has a high roughness, hydrophobicity and fair corrosion resistance. In vitro antibacterial experiments show that the BNNS_Van@CS/MAO composite coating have obvious inhibitory effect on the growth of both E. coli and S. aureus. The antibacterial effect of the BNNS_Van@CS/MAO composite coating was attributed to the synergistic effect of CS, BNNS and Van. This study provides a valuable surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance and antibacterial properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Zizyphus jujube polysaccharide was extracted with hot water, ultrahigh pressure, deep eutectic solvent (DES) and ultrahigh pressure-assisted DES. Comparative analyses were conducted on the yield, physicochemical properties and prebiotic activity of four polysaccharides (JP-H, JP-U, JP-D and JP-UD). The yield of JP-UD (10.42 %) was 3.3 times that of JP-H (3.12 %), and its sugar content was the highest. JP-UD possessed the lowest Mw, while JP-H possessed the highest. Four JPs were acidic pyranose and mainly composed of galacturonic acid, arabinose and galactose. NMR results demonstrated that they contained not only similar glycosidic linkage but also the specific glycosidic linkage of →4)-α-D-Glcp-(l→ appeared in JP-U and JP-UD, the esterified units of GalA and CONH 2 group appeared in JP-D and JP-UD, and the Terminal β-D-Galp and →4)-α-GalpA-(1→ appeared in JP-UD. JPs showed different proliferation effects on four lactobacillus strains, among which JP-UD exhibited the strongest prebiotic activity. Zizyphus jujube polysaccharides have great potential for application in the functional food and medical industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. Alveolar macrophages (AMs) are the first line immune defense in the respiratory system and play a critical role in the lung homeostasis. This study aimed to investigate the role of AMs in contributing to the protective effects of angiotensin II type-2 receptor (AT2R) activation in cigarette smoke (CS)-induced COPD. The AM polarization, phagocytosis and metabolism, and the underlying biochemical mechanisms of compound 21 (C21), a selective and potent non-peptide small molecule AT2R agonist, were evaluated in a two-week CS-induced COPD mouse model. C21 restored AM phagocytosis ability, reversing CS-induced AM phagocytosis impairment. CS exposure polarized AMs towards M1 phenotype, whereas, C21 skewed the CS-exposed AMs towards M2 phenotype. C21 reprogrammed CS-exposed AM metabolism from a high glycolysis-driven process to support inflammation energy demand to a high mitochondrial respiration process to limit inflammation. Besides, C21 upregulated AT2R and Mas receptor levels in CS-exposed AMs, favoring the anti-inflammatory Ang II/AT2R axis and Ang 1-7/Mas axis in the RAS. C21 restored the normal levels of sirtuin 1 (SIRT1) and MAPK phosphatase 1 (MKP1) in CS-exposed AMs, leading to the reduction of phospho-p38, phospho-ERK and p65 subunit of NF-κB levels in CS-exposed AMs. We report here for the first time that AT2R agonist C21 acts by boosting the protective functions of AMs against CS-induced COPD, and our results support the development of AT2R agonist for the treatment of COPD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Recessive mutations in glutamate pyruvate transaminase 2 (GPT2) have recently been found to be associated with intellectual and developmental disability (IDD). In this study, we discovered a homozygous missense variant, NM_133443: [c.1172C > T, p. Pro391Leu], of GPT2 on chromosome 16 in a proband diagnosed with IDD through trio whole-exome sequencing (WES). The pathogenicity of the variant was further verified by bioinformatics analysis and functional studies in vitro. This autosomal recessive disease was caused by paternal uniparental disomy (UPD) which was further proven by single nucleotide polymorphism array (SNP array). In past literature, recessive diseases in chromosome 16 were usually due to maternal UPD where Mendel's law of inheritance was not applicable. However, in our case we found that paternal UPD can cause recessive diseases related to the GPT2 gene on chromosome 16. Our study provides an important line of evidence for the diagnosis of GPT2-related intellectual developmental disorders., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

In developing countries, public transportation is the first choice for the elderly because of its convenience and cheapness. The high density population of public transportation increases the risk of passengers contracting infectious diseases, so it is extremely critical to determine healthy transportation systems to safeguard the health of passengers. The propagation characteristics of droplets in the ZK-type public bus were studied by computational fluid simulation employing the Realizable k-ε turbulence model and discrete phase model. The modified Wells-Riley model was used to quantitatively assess the infection risk of SARS-CoV-2 spread by droplets on the elderly. The risk assessment shows that when the personalized air supply angle is 30°, the number of infected passengers is the least, reaching 14, which shows that the infection risk of passengers can be reduced through the design of personalized air supply angle. Regardless of the angle of the personalized air supply, the rear seats are in a low-risk area. Therefore, it's recommended that elderly passengers choose the rear seats of the public bus during the epidemic to prevent being infected. This study can provide a reference for healthy transportation systems to construct a healthy environment inside the public bus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

In the last few years, with the advent of next generation sequencing (NGS), our knowledge of genes associated with monogenic epilepsies has significantly improved. NGS is also a powerful diagnostic tool for patients with epilepsy, through gene panels, exomes and genomes. This has improved diagnostic yield, reducing the time between the first seizure and a definitive molecular diagnosis. However, these developments have also increased the complexity of data interpretation, due to the large number of variants identified in a given patient and due to the phenotypic variability associated with many of the epilepsy-related genes. In this paper, we present examples of variant classification in "real life" clinic situations. We emphasize the importance of accurate phenotyping of the epilepsies including recognising variable/milder phenotypes and expansion of previously described phenotypes. There are some important issues specific to rare epilepsies - mosaicism and reduced penetrance - which affect genetic counselling. These challenges may be overcome through multidisciplinary meetings including epileptologists, pediatric neurologists, and clinical and molecular geneticists, in which every specialist learns from the others in a process which leads to for rapid and accurate diagnosis. This is an important milestone to achieve as targeted therapiesbased on the functional effects of pathogenic variants become available., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Herein, a dual-function Zeolitic Imidazole Frameworks (ZIFs) ZIF-90 grafted with malononitrile by Knoevenagel reaction and following with an amidoximation reaction to form an efficient U (VI) adsorbent (ZIF-90-AO). The strong chelation power of amidoxime groups (AO) with uranium and ZIF-90's mesoporous structure afforded ZIF-90-AO high maximum uranium adsorption capacity of 468.3 mg/g (pH = 5). In addition, the factors affecting uranium adsorption process were investigated by a batch of adsorption tests under different adsorption conditions. ZIF-90-AO displayed good selectivity to UO 2 2+ in the solution containing multiple co-existing ions and good regeneration property. More importantly, ZIF-90-AO showed excellent antimicrobial property against both E. coli and S. aureus. Therefore, ZIF-90-AO is a U-adsorbent with great application value for removing U (VI) from wastewater due to the high U (VI) adsorption capacity in weak acid condition and good anti-biofouling properties., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igβ. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The objective of this study was to identify developmental trajectories of developmental/behavioral phenotypes and possibly their relationship to epilepsy and genotype by analyzing developmental and behavioral features collected prospectively and longitudinally in a cohort of patients with Dravet syndrome (DS). Thirty-four patients from seven Italian tertiary pediatric neurology centers were enrolled in the study. All patients were examined for the SCN1A gene mutation and prospectively assessed from the first years of life with repeated full clinical observations including neurological and developmental examinations. Subjects were found to follow three neurodevelopmental trajectories. In the first group (16 patients), an initial and usually mild decline was observed between the second and the third year of life, specifically concerning visuomotor abilities, later progressing towards global involvement of all abilities. The second group (12 patients) showed an earlier onset of global developmental impairment, progressing towards a generally worse outcome. The third group of only two patients ended up with a normal neurodevelopmental quotient, but with behavioral and linguistic problems. The remaining four patients were not classifiable due to a lack of critical assessments just before developmental decline. The neurodevelopmental trajectories described in this study suggest a differential contribution of neurobiological and genetic factors. The profile of the first group, which included the largest fraction of patients, suggests that in the initial phase of the disease, visuomotor defects might play a major role in determining developmental decline. Early diagnosis of milder cases with initial visuomotor impairment may therefore provide new tools for a more accurate habilitation strategy., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. This study aimed to investigate potential protective effects of angiotensin II type-2 receptor (AT2R) activation in cigarette smoke (CS)-induced COPD models. Compound 21 (C21), a selective and potent non-peptide small molecule AT2R agonist, was evaluated for anti-inflammatory, anti-oxidative and anti-remodeling activities in a two-week (acute) and an eight-week (chronic) CS-induced COPD models. C21 inhibited CS-induced increases in macrophage and neutrophil counts, pro-inflammatory cytokines and oxidative damage markers in bronchoalveolar lavage (BAL) fluid, and TGF-β1 in lung tissues, from COPD models. C21 restored phosphatase activities and reduced phospho-p38 MAPK, phospho-ERK and p65 subunit of NF-κB levels in CS-exposed lung tissues. C21 also suppressed CS-induced increases in α-Sma, Mmp9, Mmp12 and hydroxyproline levels in lung tissues, and neutrophil elastase activity in BAL fluid. C21 modulated RAS in CS-exposed lungs by downregulating Ang II but upregulating Ang-(1-7) and Mas receptor levels. C21 prevented CS-induced emphysema and improved lung functions in chronic COPD model. We report here for the first time the protective effects of AT2R agonist C21 against CS-induced COPD, and provide strong evidence for further development of AT2R agonist for the treatment of COPD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed in vivo that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

[This corrects the article DOI: 10.1016/j.apsb.2019.03.006.]., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

This study aimed to investigate the effects of programmed cell death protein 10 (PCDP10) on the female reproductive system of Schistosoma japonicum, one of the major infectious agents of schistosomiasis. We found that PCDP10 was widely distributed in the integument, the worm parenchymal area, and the vitellarium of the female worm, but was localized to a lesser extent in the ovary and testicles. RNAi experiments successfully achieved gene knockdown, and the ultrastructural morphology of the adult reproductive organs was observed. The results demonstrated that, compared with those of the negative control group, the number of cortical granules around oocytes decreased and the number of immature oocyte cells increased. Fusion of yolk globules occurred, and the number and the diameter of yolk droplets decreased significantly. Real-time PCR showed that the expression of yolk glands reached its peak before ovulation and then decreased. The TUNEL assay results showed that apoptosis in the RNAi group was significantly higher than that in the negative control group. These results suggested that SjPCDP10 plays an important role in the female reproductive system. In conclusion, PCD10 is involved in oocyte growth and development, especially in eggshell formation, which may provide a reference for further elucidating the molecular mechanism of PCDP10 involved in egg formation and embryo development in Schistosoma japonicum., Competing Interests: Declaration of Competing Interst None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake in vitro and more tumor accumulation of micelles in vivo , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality., (© 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

A simple, rapid and sensitive HPLC-MS/MS method for simultaneous determination of 4 of amino acids, guanidinoacetic acid, S-adenosylmethionine and S-adenosylhomocysteine in human plasma was developed and validated. The method requires no tedious sample preparation, derivatization reagents or ion-pairing reagents. Samples were prepared by combining plasma with a chilled mixture of acetonitrile (ACN) and water, followed by centrifugation and diluting the supernatant with 2 volumes of water. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization (ESI). In the assay, all the analytes showed good linearity over the investigated concentration range (r > 0.99). The accuracy expressed in relative error (RE) was between -5.0% and 13.2%, and the precision expressed in coefficient of variation (CV) ranged from 0.6% to 14.7%. In the two spiked levels (low and high), the averaged recoveries of analytes were between 45.0% and 110.9% and the recovery of internal standard was 92.0%. This method was successfully applied to studying the concentration changes of endogenous creatine (Cr) synthesis precursors in the plasma of children with viral myocarditis after intravenous administration of phosphocreatine (PCr)., (Copyright © 2019. Published by Elsevier B.V.)

Heroin addiction is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits. Despite considerable advances in psychotherapy and pharmacotherapy for heroin relapse and addiction, effective treatments for heroin use disorder are still lacking. Increasing preclinical evidence indicates that heroin seeking behavior is persistent after withdrawal, while cognitive dysfunctions associated with chronic heroin use are an important contributing factor to risk of heroin relapse and addiction. Cognitive enhancers may be used to stimulate treatment success and enhance treatment efficacy. The purpose of this review is to outline the literature that demonstrates the cognitive deficits during the development of heroin addiction and withdrawal process, and several factors that underline the efficacy of cognitive enhancers for heroin use disorders. The review, then, examines the potential use and pharmacological mechanisms of cognitive enhancers that act on cholinergic, glutamatergic, dopaminergic or adrenergic pathways. It also examines the effects of compounds that alter CREB signaling and epigenetic mechanisms in animal model of heroin relapse. The current body of research reveals the new insights into the pharmacological mechanisms underlying heroin addiction and holds a significant promise for cognitive enhancers as an improved approach to treat heroin use disorder in a more efficient and persistent way., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Whether high body mass index (BMI) was associated with increased postoperative complications and unfavorable prognosis of gastric cancer (GC) patients remain controversial. In the present study, we performed a systematic review and meta-analysis to evaluate the impact of high BMI on surgical outcome, postoperative complications and long-term survival of GC patients., Methods: The related studies were identified by searching PubMed and Embase databases. According to the BMI, all GC patients were classified into BMI ≥25 kg/m 2 group and BMI <25 kg/m 2 group. The relevant data was extracted and pooled effect size was assessed using a fixed effect model or random effect model., Results: A total of 36 relevant studies involving 30,642 GC patients were included in this meta-analysis. The results indicated that high BMI patients had longer operation time, fewer number of retrieved lymph nodes and larger amount of intraoperative blood loss than other patients, regardless of open gastrectomy or laparoscopic gastrectomy. In addition, the risk of postoperative complications was significantly higher in the patients with BMI ≥25 kg/m 2 than in those with BMI <25 kg/m 2 , especially for infectious complications. However, high BMI had no negative impact on postoperative mortality and long-term survival of GC patients., Conclusion: Despite the increased surgical difficulty and postoperative complications, high BMI was not associated with the prognosis of GC patients. To reduce the risk of postoperative complications, more meticulous operation technique and improved perioperative management should be necessary for high BMI patients., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To estimate diagnostic yield and genotype-phenotype correlations in a cohort of 811 patients with lissencephaly or subcortical band heterotopia., Methods: We collected DNA from 756 children with lissencephaly over 30 years. Many were tested for deletion 17p13.3 and mutations of LIS1, DCX, and ARX, but few other genes. Among those tested, 216 remained unsolved and were tested by a targeted panel of 17 genes (ACTB, ACTG1, ARX, CRADD, DCX, LIS1, TUBA1A, TUBA8, TUBB2B, TUBB, TUBB3, TUBG1, KIF2A, KIF5C, DYNC1H1, RELN, and VLDLR) or by whole-exome sequencing. Fifty-five patients studied at another institution were added as a validation cohort., Results: The overall mutation frequency in the entire cohort was 81%. LIS1 accounted for 40% of patients, followed by DCX (23%), TUBA1A (5%), and DYNC1H1 (3%). Other genes accounted for 1% or less of patients. Nineteen percent remained unsolved, which suggests that several additional genes remain to be discovered. The majority of unsolved patients had posterior pachygyria, subcortical band heterotopia, or mild frontal pachygyria., Conclusion: The brain-imaging pattern correlates with mutations in single lissencephaly-associated genes, as well as in biological pathways. We propose the first LIS classification system based on the underlying molecular mechanisms.

Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the relationship between papillary thyroid carcinoma and environmental exposure to bisphenol A (BPA) or 17-β estrogen (E 2 ) by assessing the effects of these compounds on estrogen receptor expression and AKT/mTOR signaling., Methods: The effects of low levels of BPA (1mM-10nM) and 17β-estradiol (E2, 0.1mM-1nM) on ER expression and cellular proliferation were determined in human thyroid papillary cancer BHP10-3 cells. Protein and mRNA levels of estrogen nuclear receptors (ERα/ERβ) and membrane receptors (GPR30) were determined by immunofluorescence assay, Western blotting, and RT-PCR, respectively, and proliferation was assessed by CCK-8 assay., Results: The proliferative effects of BPA and E 2 were both concentration- and time-dependent. Expression of ERα/ERβ and GPR30 were enhanced by BPA and E 2. BPA and E 2 could quickly phosphorylate AKT/mTOR. Moreover, ICI suppressed ERα expression and activated GPR30 as did G-1. G-15 reversed the effects of E 2 on GPR30 and AKT/mTOR, but did not alter the effect of BPA., Conclusions: BPA influences thyroid cancer proliferation by regulating expression of ERs and GPR30, a mechanism that differs from E 2 . In addition, ICI and G-15 may have the potential to be used as anti-thyroid cancer agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

3D printing is emerging as a powerful tool for tissue engineering by enabling 3D cell culture within complex 3D biomimetic architectures. This review discusses the prevailing 3D printing techniques and their most recent applications in building tissue constructs. The work associated with relatively well-known inkjet and extrusion-based bioprinting is presented with the latest advances in the fields. Emphasis is put on introducing two relatively new light-assisted bioprinting techniques, including digital light processing (DLP)-based bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation. Limitations to current bioprinting approaches, as well as future directions of bioprinting functional tissues are also discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A novel beta-cyclodextrin (beta-CD) functionalized organic polymer monolith was prepared by covalently bonding ethylenediamine-beta-CD (EDA-beta-CD) to poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-co-EGDMA)) monolith via ring opening reaction of epoxy groups. SEM characterization was performed to confirm the homogeneity of the monolithic polymer. The resulting monolith was then characterized by DSC and XPS elemental analysis to study the thermal stability of the monolith, and to prove the successful immobilization of beta-CD on the polymer substrate. The beta-CD ligand density of 0.68 mmol g(-1) was obtained for the modified monolith, indicating the high reactivity and efficiency of the EDA-beta-CD modifier. The ethylenediamine-beta-CD functionalized monoliths were used for the chiral separation of ibuprofen racemic mixture and showed promising results., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Mutations of the DCX gene (Xp22.3) cause X-linked lissencephaly in males and double cortex syndrome (DCS) or subcortical band heterotopia (SBH) in females. SBH is characterized by bilateral bands of grey matter interposed in the white matter between the cortex and the lateral ventricles. The main clinical manifestation in patients with SBH is epilepsy, which may be partial or generalized and is intractable in approximately 65% of the patients. An association of periodic limb movements (PLMs) and SBH has not been documented previously. We describe a 2-year-old girl affected by SBH with epilepsy and periodic limb movements (PLMs), in whom a novel "de novo" missense substitution, Met1Val (M1V), was identified in the DCX gene. Physiopathological links between PLMs and SBH are discussed., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

To investigate the mechanisms underlying the expression of allergic contact dermatitis, we compared the characteristics of nickel (Ni)-specific T cell responses in 10 patients with allergic contact dermatitis to Ni and in 10 healthy, nonallergic individuals. CD4+ T cells purified from peripheral blood of both allergic and nonallergic subjects proliferated similarly to NiSO4 in vitro, with the responses mostly restricted to CD4+ CD45RO+ memory T cells. In contrast, Ni-specific CD8+ T cell responses were detected only in allergic patients. Limiting dilution assay confirmed a high frequency of Ni-specific CD4+ T cells in both individual categories, and of Ni-specific CD8+ T cells in allergic patients, but not in nonallergic persons. Ni-specific CD4+ T cell clones prepared from nonallergic subjects displayed lower interferon-gamma and higher interleukin-10 production compared with T cell clones from allergic patients. The T cell skin-homing receptor, cutaneous lymphocyte-associated antigen, was expressed on the large majority of specific CD4+ clones from both the groups. Finally, Ni-specific CD8+ clones prepared from patients also expressed the cutaneous lymphocyte-associated antigen receptor, and released high interferon-gamma and no interleukin-4. In aggregate, the results suggest that the presence of specific CD8+ T cells and a distinct pattern of cytokine release (e.g., an augmented production of interleukin-10) by CD4+ T cells can be important elements in determining whether a hapten induces allergy or a silent immune response.

In the myocardial interstitial space, adenosine and its metabolites are important markers of ischemia, regulators of blood flow, and may produce cardioprotection against ischemia. A fast and sensitive method to assess the concentrations of adenosine and its metabolites is necessary to determine their involvement in mediating these effects. A method for the simultaneous determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in the interstitial fluid of the canine myocardium was developed using microdialysis, microbore column high-performance liquid chromatography, and a photo diode array detector (DAD). The microdialysis samples were injected directly onto a microbore C18 reverse-phase column without any prior sample preparation. Use of a DAD in this method provided many advantages. First, a DAD allowed the simultaneous detection of UV absorbance at multiple wavelengths, allowing the detection of each compound at their maximal UV absorbance. Further, the full UV absorption spectrum was recorded for each detected peak, confirming peak purity and identity. Using a microbore HPLC column and detection of UV absorbance at the maximal absorbance for each compound improve the sensitivity for all compounds. The detection limit of these compounds is 50 fmol (signal-to-noise ratio, S/N = 3). This method is useful in analyzing the temporal effect of a prolonged period of myocardial ischemia and reperfusion upon interstitial adenosine, inosine, hypoxanthine, xanthine, and uric acid concentrations in an in vivo canine model.

Methodologies for the analysis of cadmium, copper, iron, lead, selenium and zinc in human seminal plasma and spermatozoa have been developed. Analyses were made directly in a dilution of seminal plasma or nitric acid digest of lyophilized cells using Zeeman-effect atomic absorption spectroscopy. Within-run coefficients of variation (CV's) for pooled specimens ranged from 0.5% to 9%. Between-run CV's ranged from 4% to 13%. Analysis of a seminal plasma specimen at 1/2, 1, 1 1/2, 3 1/2 and 5 hours post emission indicated that no change in seminal plasma trace element concentrations occurred on standing in contact with spermatozoa. Trace element concentrations were determined in specimens from patients undergoing infertility studies.