Unveiling the Mechanism of Plasma-Catalyzed Oxidation of Methane to C2+ Oxygenates over Cu/UiO-66-NH2.

Nonthermal plasma (NTP) offers the potential for converting CH4 with CO2 into liquid products under mild conditions, but controlling liquid selectivity and manipulating intermediate species remain significant challenges. Here, we demonstrate the effectiveness of the Cu/UiO-66-NH2 catalyst in promising the conversion of CH4 and CO2 into oxygenates within a dielectric barrier discharge NTP reactor under ambient conditions. The 10% Cu/UiO-66-NH2 catalyst achieved an impressive 53.4% overall liquid selectivity, with C2+ oxygenates accounting for ∼60.8% of the total liquid products. In situ plasma-coupled Fourier-transform infrared spectroscopy (FTIR) suggests that Cu facilitates the cleavage of surface adsorbed COOH species (*COOH), generating *CO and enabling its migration to the surface of Cu particles. This surface-bound *CO then undergoes C-C coupling and hydrogenation, leading to ethanol production. Further analysis using CO diffuse reflection FTIR and 1H nuclear magnetic resonance spectroscopy indicates that in situ generated surface *CO is more effective than gas-phase CO (g) in promoting C-C coupling and C2+ liquid formation. This work provides valuable mechanistic insights into C-C coupling and C2+ liquid production during plasma-catalytic CO2 oxidation of CH4 under ambient conditions. These findings hold broader implications for the rational design of more efficient catalysts for this reaction, paving the way for advancements in sustainable fuel and chemical production.

Association between the dietary inflammatory index and pelvic inflammatory disease - Findings from the NHANES data (2015-2018).

BACKGROUND: pelvic inflammatory disease (PID) is a common gynecological condition. The dietary inflammatory index (DII) scoring algorithm is a novel tool for evaluating the inflammatory potential of a diet. However, the association between DII and PID remains unexplored. This study aimed to evaluate and quantify the relationship between DII and the risk for PID. MATERIAL AND METHODS: the present study included two cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2018. A total of 2769 participants with complete information were enrolled. Weighted univariate and multivariate logistic regression analyses were performed to examine the association between DII and the risk for PID. Subsequently, the association was graphically represented using a restricted cubic spline (RCS). RESULTS: univariate and multivariate regression analyses revealed a strong correlation between DII and PID occurrence. After adjusting for all covariates, the odds ratio for the effect of DII on PID remained significant (OR = 1.220, 95 % CI: 1.024-1.452). The correlation analysis revealed a linear relationship between DII and the risk for PID. CONCLUSIONS: This study unravels a significant positive correlation between DII and the risk for PID. This finding highlights the potential of anti-inflammatory diet therapy as a novel therapeutic intervention for PID. However, due to the limitations of the study design, further research is needed to explore this relationship in detail.

Cai's prescription inhibits granulosa cell apoptosis through ARHGAP4 on poor ovarian responders.

PURPOSE: Poor ovarian response (POR) is a big challenge for in vitro fertilization. The traditional Chinese medicine, Cai's Prescription of Tonifying Kidney and Strengthening Vitals (Cai's Prescription) has yielded satisfactory results for POR treatment clinically, but systematic scientific research of Cai's Prescription is not well reported. This study aimed to investigate the clinical effect of Cai's Prescription on poor ovarian responders and its biological mechanism. METHODS: Serum was collected from poor ovarian responders, and IL-1ß, INFγ, FSH, E2 and AMH levels were analyzed by ELISA. Ovarian antral follicles were identified and counted using transvaginal ultrasound. The embryo quality grading were done on day 3 after retrieval. We used high-throughput sequencing of granulosa cells to investigate the gene transcription patterns of ovarian granulosa cells in poor ovarian responders after Cai's Prescription pretreatment. The expression level of ARHGAP4 was analyzed by quantitative real-time PCR and western blot. The effects of ARHGAP4 for granulosa cells were analyzed by CCK-8 assay, annexin-V and PI staining, ELISA and western blot. The effects of Cai's Prescription on the expression of PI3K-Akt pathway and apoptosis were analyzed by western blot. RESULTS: In this study, we found that Cai's Prescription pretreatment had the tendency to improve the ovarian reserve function and could increase the number of high quality embryos for poor ovarian responders. Through high-throughput sequencing of mRNA in granulosa cells, we discovered ARHGAP4, which is a member of GTPase-activating proteins (GAPs) may be a candidate target for POR treatment. ARHGAP4 was significantly increased in poor ovarian responders and can be recovered after Cai's Prescription pretreatment. Mechanically, combining the cell line model and clinical tissue samples, we found that ARHGAP4 can accelerate cell apoptosis and inflammation response in granulosa cells via PI3K-Akt signaling pathway. In addition, Cai's Prescription pretreatment for three months significantly reduced the high level of ARHGAP4 in poor ovarian responders. CONCLUSION: This study shows that the traditional Chinese medicine, Cai's Prescription yielded satisfactory results for poor ovarian responders clinically and ARHGAP4 may be a candidate target for POR treatment.

Association between dietary trace minerals and pelvic inflammatory disease: data from the 2015-2018 National Health and Nutrition Examination Surveys.

Objective: Pelvic inflammatory disease (PID) is a prevalent gynecological disorder. Dietary trace minerals play an important role in combating many chronic diseases including PID. However, it is unknown whether dietary trace minerals and PID are related. This study aimed to examine the relationship between dietary trace minerals (copper, iron, selenium, and zinc) and PID. Methods: Data of women participants from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were enrolled in this cross-sectional investigation. Univariate and multivariate linear regression analyses of the relationship between dietary trace minerals and PID were performed, and restricted cubic spline (RCS) analyses were applied to visualize those relationships. Results: In total, 2,694 women between the ages of 20 and 59 years participated in the two NHANES cycles. In the univariate analyses, a significant negative relationship was identified between PID and dietary copper intake [odds ratio (OR) = 0.40, 95% confidence interval (CI): 0.24-0.67, p < 0.01] but not with iron (OR = 0.96, 95% CI: 0.90-1.03, p = 0.25), selenium (OR = 1.0, 95% CI: 0.99-1.0, p = 0.23), and zinc (OR = 0.94, 95% CI: 0.86-1.03, p = 0.17) intake. Following the adjustment for age and race (model 1), a robust correlation was found between dietary copper intake and PID (OR = 0.23, 95% CI = 0.09-0.61, p < 0.01), as indicated by the fully adjusted model 2 (OR = 0.29, 95% CI = 0.09-0.90, p = 0.03). Simultaneously, a significant trend was found between copper intake and PID across the quintile subgroups (p for trends <0.05), suggesting a robust relationship. Furthermore, the RCS analysis demonstrated a linear correlation between PID and dietary copper intake (overall p < 0.01, non-linear p = 0.09). Conclusion: Decreased dietary copper intakes are linked to PID. However, additional research is needed to fully investigate this relationship due to the constraints of the study design.

High-throughput sequencing reveals hub genes for human early embryonic development arrest in vitro fertilization: a pilot study.

Many clinical studies have shown that embryos of in vitro fertilization (IVF) are often prone to developmental arrest, which leads to recurrent failure of IVF treatment. Early embryonic arrest has always been an urgent clinical problem in assisted reproduction centers. However, the molecular mechanisms underlying early embryonic development arrest remain largely unknown. The objective of this study is to investigate potential candidate hub genes and key signaling pathways involved in early stages of embryonic development. RNA-seq analysis was performed on normal and arrest embryos to study the changes of gene expression during early embryonic development. A total of 520 genes exhibiting differential expression were identified, with 174 genes being upregulated and 346 genes being downregulated. Upregulated genes show enrichment in biosynthesis, cellular proliferation and differentiation, and epigenetic regulation. While downregulated genes exhibit enrichment in transcriptional activity, epigenetic regulation, cell cycle progression, cellular proliferation and ubiquitination. The STRING (search tool for the retravel of interacting genes/proteins) database was utilized to analyze protein-protein interactions among these genes, aiming to enhance comprehension of the potential role of these differentially expressed genes (DEGs). A total of 22 hub genes (highly connected genes) were identified among the DEGs using Cytoscape software. Of these, ERBB2 and VEGFA were upregulated, while the remaining 20 genes (CCNB1, CCNA2, DICER1, NOTCH1, UBE2B, UBE2N, PRMT5, UBE2D1, MAPK3, SOX9, UBE2C, UB2D2, EGF, ACTB, UBA52, SHH, KRAS, UBE2E1, ADAM17 and BRCA2) were downregulated. These hub genes are associated with crucial biological processes such as ubiquitination, cellular senescence, cell proliferation and differentiation, and cell cycle. Among these hub genes, CCNA2 and CCNB1 may be involved in controlling cell cycle, which are critical process in early embryonic development.

Association between heavy metal exposures and the prevalence of pelvic inflammatory disease: a cross-sectional study from the National Health and Nutrition Examination Survey 2013-2018.

Pelvic inflammatory disease (PID) is a common medical condition in women. However, the correlation between exposure to heavy metals, including cadmium (Cd), lead (Pb), manganese (Mn), mercury (Hg), and selenium (Se), and PID, is unclear. Using a large sample size from the National Health and Nutrition Examination Survey, these relationships were studied and verified. PID diagnosis was acquired through a self-reported questionnaire (2013-2018). Heavy metal exposure (Cd, Pb, Mn, Hg, and Se) was measured using mass spectrometry of blood samples. Covariate data were obtained through questionnaires and physical tests. Individuals with complete covariate data were included in the study. The relationship between heavy metal exposure (Cd, Pb, Mn, Hg, and Se) and PID was demonstrated using logistic regression analysis, weighted quantile sum (WQS) regression analysis, and restricted cubic splines (RCS). Overall, 2743 participants were included. Of these, 183 were diagnosed with PID. Through weighted univariate and multivariate regression analyses, the heavy metals of Cd and Pb were positively correlated with the prevalence of PID. However, no significant relationship was observed in the heavy metals of Mn, Hg, and Se. The joint effect of heavy metals further confirmed the important role of Cd and Pb in WQS analysis. After visualizing the RCS, significant curved and linear relationships were observed for Cd and Pb, respectively. Most subgroup analyses confirmed these results. In conclusion, exposure to Cd was nonlinearly correlated with the risk of PID, whereas exposure to Pb showed a linear relationship. Our findings increase the awareness of the environmental effects of exposure to heavy metals in PID. However, further studies are needed to elucidate the causality and underlying mechanisms between heavy metal exposure and the prevalence of PID.

Effects of body mass index on IVF outcomes in different age groups.

BACKGROUND: Herein, we aimed to analyse the effects of body mass index (BMI) on the treatment outcomes of in vitro fertilisation (IVF) in a cohort of women undergoing their first IVF cycle. METHODS: A total of 2311 cycles from 986 women undergoing their first IVF/intracytoplasmic sperm injection cycle with fresh/frozen embryo transfer between January 2018 and December 2021 at the Center of Reproductive Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, were considered in this retrospective cohort study. First, the included patients were classified into four groups based on their BMI: underweight (BMI < 18.5 kg/m2, 78 patients), normal weight (18.5 ≤ BMI < 24 kg/m2, 721patients), overweight (24 ≤ BMI < 28 kg/m2, 147 patients), and obese (BMI ≥ 28 kg/m2, 40 patients). The IVF outcomes included the Gn medication days; Gn dosage; number of retrieved oocytes, mature oocytes, fertilized oocytes, cleavages, and available embryos and high-quality embryos; implantation rate; clinical pregnancy rate and live birth rate. Next, all the obtained data were segregated into three different subgroups according to the patient age: < 30 years, 30-38 years and > 38 years; the IVF pregnancy outcomes were compared among the groups. RESULTS: Compared with the other three groups, the underweight group had a higher number of fertilized oocytes, cleavage and available embryos and a smaller Gn medication days and required a lower Gn dosage. There was no difference in the number of retrieved oocytes and mature oocytes among the groups. Moreover, compared with the women aged 30-38 years in the overweight group, those in the normal weight group had a significantly higher implantation rate, clinical pregnancy rate and live birth rate (p = 0.013 OR 1.75, p = 0.033 OR 1.735, p = 0.020 OR 1.252 respectively). The clinical pregnancy rate was also significantly higher in those aged 30-38 years in the normal weight group than in the obese group (p = 0.036 OR 4.236). CONCLUSIONS: Although the BMI can greatly affect the pregnancy outcomes of women aged 30-38 years, it has almost no effects on the outcomes of younger or older women.

Cl2 ⋠- Mediates Direct and Selective Conversion of Inert C(sp3 )-H Bonds into Aldehydes/Ketones.

Developing new reactive pathway to activate inert C(sp3 )-H bonds for valuable oxygenated products remains a challenge. We prepared a series of triazine conjugated organic polymers to photoactivate C-H into aldehyde/ketone via O2 →H2 O2 →⋅OH→Cl⋅→Cl2 ⋅- . Experiment results showed Cl2 ⋅- could successively activate C(sp3 )-H more effectively than Cl⋅ to generate unstable dichlorinated intermediates, increasing the kinetic rate ratio of dichlorination to monochlorination by a factor of 2,000 and thus breaking traditional dichlorination kinetic constraints. These active intermediates were hydrolyzed into aldehydes or ketones easily, when compared with typical stable dichlorinated complexes, avoiding chlorinated by-product generation. Moreover, an integrated two-phase system in an acid solution strengthened the Cl2 ⋅- mediated process and inhibited product overoxidation, where the conversion rate of toluene reached 16.94 mmol/g/h and the selectivity of benzaldehyde was 99.5 %. This work presents a facile and efficient approach for selective conversion of inert C(sp3 )-H bonds using Cl2 ⋅- .

Review of Konjac Glucomannan Structure, Properties, Gelation Mechanism, and Application in Medical Biology.

Konjac glucomannan (KGM) is a naturally occurring macromolecular polysaccharide that exhibits remarkable film-forming and gel-forming properties, and a high degree of biocompatibility and biodegradability. The helical structure of KGM is maintained by the acetyl group, which plays a crucial role in preserving its structural integrity. Various degradation methods, including the topological structure, can enhance the stability of KGM and improve its biological activity. Recent research has focused on modifying KGM to enhance its properties, utilizing multi-scale simulation, mechanical experiments, and biosensor research. This review presents a comprehensive overview of the structure and properties of KGM, recent advancements in non-alkali thermally irreversible gel research, and its applications in biomedical materials and related areas of research. Additionally, this review outlines prospects for future KGM research, providing valuable research ideas for follow-up experiments.

Structure, Merits, Gel Formation, Gel Preparation and Functions of Konjac Glucomannan and Its Application in Aquatic Food Preservation.

Konjac glucomannan (KGM) is a natural polysaccharide extracted from konjac tubers that has a topological structure composed of glucose and mannose. KGM can be used as a gel carrier to load active molecules in food preservation. The three-dimensional gel network structure based on KGM provides good protection for the loaded active molecules and allows for sustained release, thus enhancing the antioxidant and antimicrobial activities of these molecules. KGM loaded with various active molecules has been used in aquatic foods preservation, with great potential for different food preservation applications. This review summarizes recent advances in KGM, including: (i) structural characterization, (ii) the formation mechanism, (iii) preparation methods, (iv) functional properties and (v) the preservation of aquatic food.

Sulfone-Decorated Conjugated Organic Polymers Activate Oxygen for Photocatalytic Methane Conversion.

Oxidizing CH4 into liquid products with O2 under mild conditions still mainly relies on metal catalysis. We prepared a series of sulfone-modified conjugated organic polymers and found that the catalyst with proper SVI content (0.10) could drive O2 →H2 O2 →⋅OH to oxidize CH4 into CH3 OH and HCOOH directly and efficiently at room temperature under light irradiation. Experimental results showed that after 4 h reaction, decomposition rate and residual amounts of H2 O2 were 81.21 % and 4.83 mmol gcat -1 respectively, and CH4 conversion rate was 22.81 %. Mechanism studies revealed that illumination could induce the homolytic dissociation of S=O bonds on catalyst to produce oxygen and sulfur radicals, where the ⋅O could adsorb and activate CH4 , and the ⋅S could supply electrons for 1 O2 to generate H2 O2 and then for decomposing the H2 O2 into ⋅OH timely to oxidize CH4 . This research provided a novel organic catalysis approach for oxygen activation and utilization.

UHPLC-MS-MS analysis of oxylipins metabolomics components of follicular fluid in infertile individuals with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes in the ovary, which results in a lack of sex hormones and a decline of fertility in women. DOR can potentially progress to premature ovarian failure (POF), which has a negative impact on women's quality of life and is a major cause of female infertility. Oxidative stress is a major contributor to fertility decrease in DOR patients, affecting the follicular microenvironment, oocyte maturation, fertilization, and embryo development. Understanding intracellular signal transduction can be achieved by defining specific oxidized lipid components in follicular fluid (FF) of DOR infertile patients. METHODS: The oxylipins metabolic signatures in the FF of DOR patients and females with normal ovarian reserve (NOR) enrolled for the in vitro fertilization (IVF) cycle were analyzed using UHPLC-MS-MS technology. Principal component analysis (PCA) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) were used to analyze the derived metabolomic profiles. Pathway enrichment analysis was carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst databases. Furthermore, the Spearman rank correlation coefficient was used to determine the correlation between age, FSH, AMH, AFC, oocytes retrieved, MII oocytes, fertilization, high-quality embryos, and the concentration of differential oxidized lipid metabolites in FF. RESULTS: Fifteen oxylipins metabolites were found to be lower in the FF of DOR patients than those in the NOR group, including ±20-HDoHE, ±5-iso PGF2α-VI, 12S-HHTrE, 15-deoxy-Δ12,14-PGJ2, 1a,1b-dihomo PGE2, 1a,1b-dihomo PGF2α, 20-COOH-AA, 20-HETE, 8S,15S-DiHETE, PGA2, PGD2, PGE1, PGF1α, PGF2α, and PGJ2. The pathway enrichment analysis revealed that the 15 differentially oxidized lipid metabolites were closely related to the arachidonic acid metabolic pathway. Correlation analysis revealed that the concentration of 8 different oxidized lipid metabolites in FF was negatively correlated to FSH and positively correlated with AFC. AMH, the number of oocytes retrieved, MII oocytes and fertilization, were all positively correlated with 9 different oxidized lipid metabolites, but only one metabolite was positively correlated with the number of high-quality embryos. CONCLUSIONS: Metabolomic analysis of FF revealed that oxylipins metabolism disorders were closely related to ovarian reserve function. Among these oxylipins metabolites, arachidonic acid metabolism undergoes significant changes that may be related to oocyte development, resulting in decreased fertility in DOR patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2000038182 , Registered 12 September 2020-Retrospectively registered.

Cu,Zn Dopants Boost Electron Transfer of Carbon Dots for Antioxidation.

Enzyme-mimicking nanomaterials for antioxidative therapy is a promising star to treat more than 200 diseases or control their progressions through scavenging excessive reactive oxygen species (ROS), such as O2•- and H2 O2 . However, they can inversely produce stronger ROS (e.g., •OH) under many disease conditions (e.g., low pH for myocardial ischemia). Herein, a biocompatible -Cu-O-Zn- bimetallic covalent doped carbon dots (CuZn-CDs) processing both catalase (CAT) and superoxide dismutase activities are reported, mainly because of their abundant electrons and the excellent electron transfer abilities. In addition, Cu dopant helps to balance the positive charge at Zn dopant resulting from low pH, enabling CuZn-CDs to still process CAT ability rather than peroxidase ability. Benefiting from it, CuZn-CDs exhibit sufficient in vitro ROS scavenging ability and cardiomyocyte protective effect against ROS-induced damage. In vivo results further demonstrate that CuZn-CDs can protect the heart from ischemia-reperfusion injury. In addition to antioxidative therapy, the rapid renal clearance and low toxicity properties of CuZn-CDs in animal model reveal high biocompatibility which will facilitate clinical use.

Exosome-Contained APOH Associated With Antiphospholipid Syndrome.

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disease that can lead to thrombosis and/or pregnancy complications. Exosomes, membrane-encapsulated vesicles that are released into the extracellular environment by many types of cells, can carry signals to recipient cells to affect angiogenesis, apoptosis, and inflammation. There is increasing evidence suggesting that exosomes play critical roles in pregnancy. However, the contribution of exosomes to APS is still unknown. Methods: Peripheral plasma was collected from healthy early pregnancy patients (NC-exos) and early pregnancy patients with APS (APS-exos) for exosome extraction and characterization. The effect of exosomes from different sources on pregnancy outcomes was determined by establishing a mouse pregnancy model. Following the coincubation of exosomes and human umbilical vein endothelial cells (HUVECs), functional tests examined the features of APS-exos. The APS-exos and NC-exos were analyzed by quantitative proteomics of whole protein tandem mass tag (TMT) markers to explore the different compositions and identify key proteins. After incubation with HUVECs, functional tests investigated the characteristics of key exosomal proteins. Western blot analysis was used to identify the key pathways. Results: In the mouse model, APS-exos caused an APS-like birth outcome. In vitro experiments showed that APS-exos inhibited the migration and tube formation of HUVECs. Quantitative proteomics analysis identified 27 upregulated proteins and 9 downregulated proteins in APS-exos versus NC-exos. We hypothesized that apolipoprotein H (APOH) may be a core protein, and the analysis of clinical samples was consistent with finding from the proteomic TMT analysis. APOH-exos led to APS-like birth outcomes. APOH-exos directly enter HUVECs and may play a role through the phospho-extracellular signal-regulated kinase pathway. Conclusions: Our study suggests that both APS-exos and APOH-exos impair vascular development and lead to pregnancy complications. APOH-exos may be key actors in the pathogenesis of APS. This study provides new insights into the pathogenesis of APS and potential new targets for therapeutic intervention.

Compound heterozygous variants of the FBXO7 gene resulting in infantile-onset Parkinsonian-pyramidal syndrome in siblings of a Chinese family.

BACKGROUND: Mutations in the FBXO7 gene can cause a rare chromosomal recessive neurodegenerative disease, Parkinsonian-pyramidal syndrome (PPS). Patients with this syndrome mainly show early-onset Parkinson's syndrome. Here, we present a Chinese family with infantile-onset PPS caused by FBXO7 mutations. METHODS: The clinical phenotypes and medical records of the proband and his family members were collected. The proband, his sibling, and his parents underwent whole-exome sequencing (WES) by next-generation sequencing. RESULTS: The proband and his sibling had a typical PPS phenotype with onset during infancy. WES identified compound heterozygous variants in the FBXO7 gene, including a nonsense mutation, p. Trp134*, and a splicing mutation, IVS5-1G > A, which were shared by both siblings and inherited from each of the parents. These variants have not been reported in literatures or databases. According to the American College of Medical Genetics and Genomics guidelines, the p. Trp134* and IVS5-1G > A mutations were classified as pathogenic variants. CONCLUSIONS: We report a case of siblings in a Chinese family with infantile-onset PPS caused by FBXO7 gene mutations determined by WES. These findings will contribute to the in-depth study of the pathogenesis of PPS among patients with FBXO7 gene mutations.

Screening of PAH Common Mutations in Chinese Phenylketonuria Patients Using iPLEX MALDI-TOF MS.

Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) gene variants. Previous research has identified some PAH mutation hotspots in Chinese patients with PKU. In this study, we introduce a novel MassArray panel for screening the 29 common PAH gene mutations in Chinese patients using iPLEX MALDI-TOF MS. 105 Patients with PKU and known PAH gene mutations were genotyped using this MassArray panel. All of the 29 mutations screened were detected, and MassArray panel results were consistent with those obtained by Sanger sequencing. Fifty patients newly diagnosed with PKU were recruited in the double-blind experiment. PAH gene variants were detected in these 50 patients using the MassArray panel, and the results were verified with Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) methods. Our results show that the mutation detection rate using the MassArray panel with 29 mutations is 74% (95% CI, 65-83%), and the clinical genetic diagnosis rate is 54% (95% CI, 40-68%). This panel can be used as a high throughput, low cost, and rapid method for screening and diagnosing PAH gene mutations. The establishment of this approach provides proof-of-concept for future large-scale PAH mutation carrier screening in areas with high rates of PKU.

Tuning slow magnetic relaxation behaviour in a {Dy2}-based one-dimensional chain via crystal field perturbation.

Two novel {Dy2}-based one dimensional chain compounds {[Dy2(H3L)4(OAc)6]·2MeOH} n (1) and {[Dy2(H3L)4(OAc)4(NCS)2]·2MeOH} n (2) (H3L = 1,3-bis(2-hydroxynaphthalenemethyleneamino)-propan-2-ol) have been prepared under solvothermal conditions. Crystal structure analyses indicate that 1 and 2 feature similar 1D chain structures bearing dinuclear secondary building units. The difference between these two structures is that one chelated acetate ligand of Dy(iii) ion in 1 is replaced by one monodentate coordinated NCS- ion in 2, leading to their different coordination numbers and geometry configurations to Dy(iii) ion. Magnetic properties indicate that 1 and 2 display slow magnetic relaxation behavior with an effective energy barrier of 16.44(2) K in 1 and 8.02(2) K in 2, respectively, which is maybe attributed to the subtle crystal field perturbation of Dy(iii) ions.

Evaluation of droplet digital PCR for non-invasive prenatal diagnosis of phenylketonuria.

This study was carried out to establish a non-invasive prenatal diagnosis method for phenylketonuria (PKU) based on droplet digital PCR (ddPCR) and to evaluate its accuracy by comparison with conventional invasive diagnostic methods. A total of 24 PKU pedigrees that required prenatal diagnosis were studied, in which the genetic mutations in the probands and parents were unambiguous. Prenatal diagnosis of sibling fetuses was performed using traditional invasive prenatal diagnostic methods as a standard. At the same time, cell-free DNA (cfDNA) was extracted from maternal plasma and the fetal genes contained within were typed and quantified using ddPCR method. Invasive prenatal diagnosis determined that 3 of the 24 fetuses were affected, 8 of them were normal, and 13 were heterozygous carriers of pathogenic mutations. Successful non-invasive prenatal diagnosis analysis of PAH gene mutations was performed for 8 of the families using ddPCR method. Non-invasive prenatal diagnosis results were consistent with the results of the invasive prenatal diagnoses and no false positive or false negative results were found. In conclusion, this study is the first to establish non-invasive prenatal diagnosis of PKU based on ddPCR. The method showed high sensitivity and specificity from cfDNA, indicating that ddPCR is a reliable non-invasive prenatal diagnosis tool for PKU diagnosis. Graphical abstract.

Mutation spectrum of PAH gene in phenylketonuria patients in Northwest China: identification of twenty novel variants.

This study was performed to analyze the mutational spectrum of the phenylalanine hydroxylase (PAH) gene in phenylketonuria (PKU) patients in Northwest China, to identify mutational hot spots, and to determine the correlation between variants and clinical phenotypes of PKU. A large cohort of 475 PKU families in Northwest China was enrolled to analyze PAH gene variants using Sanger sequencing, Multiplex ligation-dependent probe amplification (MLPA), and gap-PCR. Bioinformatics software was used to predict the pathogenicity of novel variants and analyze the correlations between PAH gene variants and phenotypes of PKU patients. A total of 895 variants were detected in the 950 alleles of 475 patients with PKU (detection rate: 94.21%), 20 of which were novel variants. Other 108, previously known variants, were also identified, with the three most frequent variants being p.Arg243Gln (14.00%), c.611A > G (5.58%), and p.Tyr356* (4.95%). Seven different large deletion/duplication variants were identified by the MLPA method, including the large deletion c.-4163_-406del3758 with high frequency. A correlation analysis between patient phenotype and gene variant frequency showed that p.Arg53His and p.Gln419Arg were correlated with mild hyperphenylalaninemia (MHP). In conclusion, the mutational spectrum underlying PKU in Northwest China was established for the first time. Functional analysis of 20 novel PAH gene variants enriched the PAH gene mutational spectrum. Correlation analysis between variants frequencies in compound heterozygous patients and phenotype severity is helpful for phenotypic prediction.

Pharmacokinetics of cisplatin in the absence or presence of zengmian yiliu granules (a traditional Chinese medicine compound) in rats determined via ICP-MS: an investigation on drug-herb interactions.

CONTEXT: Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it has potent adverse effects. Zengmian Yiliu granule (ZMYL), a traditional Chinese medicine (TCM) compound, has been clinically used against platinum (Pt)-induced toxicity and to enhance the efficacy of cisplatin. OBJECTIVE: The study was conducted to investigate the likelihood of potential pharmacokinetics drug-herbs interaction (DHI) between cisplatin and ZMYL. MATERIALS AND METHODS: An improved ICP-MS method combined with ultrafiltration and microwave-assisted digestion was performed to determine the total and free Pt concentrations in rat plasma after intraperitoneal administration of cisplatin (9 mg/kg) or a combined administration with ZMYL (1 g/kg) by gavage. RESULTS: ZMYL produced a potential DHI on the pharmacokinetic parameters of cisplatin, calculated from the total Pt concentration. The clearance rate decreased from 110.52 to 66.12 mLh(-1 )kg(-1), the mean residence time extended from 63.1 to 164.54 h, the area under the plasma concentration-time curve increased from 86.58 to 152.93 µg h mL(-1), the elimination half-life extended from 48.38 to 126.4 h, and the elimination rate constant decreased from 0.017 to 0.006 h, in the ZMYL combination group (p < 0.05). In terms of free Pt concentration, the apparent volume of distribution and clearance rate was statistically different (p < 0.05). The Pt plasma protein binding ratios in the early dose stages were significantly boosted by the co-administration of ZMYL (p < 0.01). DISCUSSION AND CONCLUSION: ZMYL is a potential complementary and alternative medicine for cisplatin chemotherapy. The therapeutic benefits of ZMYL-cisplatin chemotherapy derived from pharmacokinetic interaction needs further investigation.