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1.
ACS Omega ; 9(18): 20176-20184, 2024 May 07.
Article En | MEDLINE | ID: mdl-38737044

The presence of salinity affects the accuracy of existing correlations used in the equation of state. Moreover, the variation of salinity is often ignored in the systematic analysis of the phase diagram, resulting in a large error in the final calculation result. It is obvious that the conventional phase equilibrium calculation is not applicable in a high-salinity reservoir. By introducing the hydrocarbon-brine binary interaction coefficient and α-function, combined with the definition of salinity, and considering the variation of salinity under different pressure and temperature conditions, a more perfect phase equilibrium calculation model was established. The complete phase diagram was drawn, and the calculation results of salinity distribution are obtained. The effect of the mole percentage of water and salt content on the phase behavior was simulated. Finally, the phase distribution simulation is carried out based on the measured data. The phase state and salinity variation law of a high-salinity reservoir are obtained. According to the fluid composition of different periods, the real phase state of the high-salinity reservoir can be monitored in real time. It can provide a theoretical basis for the gas reservoir development and the dynamic evaluation of gas storage injection and production with a hydrocarbon-brine two-phase system.

2.
BMC Plant Biol ; 24(1): 441, 2024 May 23.
Article En | MEDLINE | ID: mdl-38778301

BACKGROUND: Goji (Lycium barbarum L.) is a perennial deciduous shrub widely distributed in arid and semiarid regions of Northwest China. It is highly valued for its medicinal and functional properties. Most goji varieties are naturally self-incompatible, posing challenges in breeding and cultivation. Self-incompatibility is a complex genetic trait, with ongoing debates regarding the number of self-incompatible loci. To date, no genetic mappings has been conducted for S loci or other loci related to self-incompatibility in goji. RESULTS: We used genome resequencing to create a high-resolution map for detecting de novo single-nucleotide polymorphisms (SNP) in goji. We focused on 229 F1 individuals from self-compatible '13-19' and self-incompatible 'new 9' varieties. Subsequently, we conducted a quantitative trait locus (QTL) analysis on traits associated with self-compatibility in goji berries. The genetic map consisted of 249,327 SNPs distributed across 12 linkage groups (LGs), spanning a total distance of 1243.74 cM, with an average interval of 0.002 cM. Phenotypic data related to self-incompatibility, such as average fruit weight, fruit rate, compatibility index, and comparable compatibility index after self-pollination and geitonogamy, were collected for the years 2021-2022, as well as for an extra year representing the mean data from 2021 to 2022 (2021/22). A total of 43 significant QTL, corresponding to multiple traits were identified, accounting for more than 11% of the observed phenotypic variation. Notably, a specific QTL on chromosome 2 consistently appeared across different years, irrespective of the relationship between self-pollination and geitonogamy. Within the localization interval, 1180 genes were annotated, including Lba02g01102 (annotated as an S-RNase gene), which showed pistil-specific expression. Cloning of S-RNase genes revealed that the parents had two different S-RNase alleles, namely S1S11 and S2S8. S-genotype identification of the F1 population indicated segregation of the four S-alleles from the parents in the offspring, with the type of S-RNase gene significantly associated with self-compatibility. CONCLUSIONS: In summary, our study provides valuable insights into the genetic mechanism underlying self-compatibility in goji berries. This highlights the importance of further positional cloning investigations and emphasizes the importance of integration of marker-assisted selection in goji breeding programs.


Chromosome Mapping , Fruit , Lycium , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Lycium/genetics , Lycium/physiology , Fruit/genetics , Fruit/physiology , Self-Incompatibility in Flowering Plants/genetics , Phenotype , China
3.
Plants (Basel) ; 13(6)2024 Mar 20.
Article En | MEDLINE | ID: mdl-38592885

The characterization of the PYL/RCAR ABA receptors in a great deal of plant species has dramatically advanced the study of ABA functions involved in key physiological processes. However, the genes in this family are still unclear in Lycium (Goji) plants, one of the well-known economically, medicinally, and ecologically valuable fruit crops. In the present work, 12 homologs of Arabidopsis PYL/RCAR ABA receptors were first identified and characterized from Lycium (L.) barbarum (LbPYLs). The quantitative real-time PCR (qRT-PCR) analysis showed that these genes had clear tissue-specific expression patterns, and most of them were transcribed in the root with the largest amount. Among the three subfamilies, while the Group I and Group III members were down-regulated by extraneous ABA, the Group II members were up-regulated. At 42 °C, most transcripts showed a rapid and violent up-regulation response to higher temperature, especially members of Group II. One of the genes in the Group II members, LbPYL10, was further functionally validated by virus-induced gene silencing (VIGS) technology. LbPYL10 positively regulates heat stress tolerance in L. barbarum by alleviating chlorophyll degradation, thus maintaining chlorophyll stability. Integrating the endogenous ABA level increase following heat stress, it may be concluded that LbPYL-mediated ABA signaling plays a vital role in the thermotolerance of L. barbarum plants. Our results highlight the strong potential of LbPYL genes in breeding genetically modified L. barbarum crops that acclimate to climate change.

4.
Plants (Basel) ; 13(3)2024 Feb 02.
Article En | MEDLINE | ID: mdl-38337972

Lycium chinense, a type of medicinal and edible plant, is rich in bioactive compounds beneficial to human health. In order to meet the market requirements for the yield and quality of L. chinense, polyploid induction is usually an effective way to increase plant biomass and improve the content of bioactive components. This study established the most effective tetraploid induction protocol by assessing various preculture durations, colchicine concentrations, and exposure times. The peak tetraploid induction efficacy, 18.2%, was achieved with a 12-day preculture and 24-h exposure to 50 mg L-1 colchicine. Compared to diploids, tetraploids exhibited potentially advantageous characteristics such as larger leaves, more robust stems, and faster growth rates. Physiologically, tetraploids demonstrated increased stomatal size and chloroplast count in stomata but reduced stomatal density. Nutrient analysis revealed a substantial increase in polysaccharides, calcium, iron, and zinc in tetraploid leaves. In addition, seventeen carotenoids were identified in the leaves of L. chinense. Compared to the diploid, lutein, ß-carotene, neoxanthin, violaxanthin, and (E/Z)-phytoene exhibited higher levels in tetraploid strains T39 and T1, with T39 demonstrating a greater accumulation than T1. The findings suggest that the generated tetraploids harbor potential for further exploitation and lay the foundation for the selection and breeding of novel genetic resources of Lycium.

5.
Plants (Basel) ; 12(15)2023 Jul 27.
Article En | MEDLINE | ID: mdl-37570945

Carotenoids in goji (Lycium barbarum L.) have excellent health benefits, but the underlying mechanism of carotenoid synthesis and color formation in goji fruit ripening is still unclear. The present study uses transcriptomics and metabolomics to investigate carotenoid biosynthesis and color formation differences in N1 (red fruit) and N1Y (yellow fruit) at three stages of ripening. Twenty-seven carotenoids were identified in N1 and N1Y fruits during the M1, M2, and M3 periods, with the M2 and M3 periods being critical for the difference in carotenoid and color between N1 and N1Y fruit. Weighted gene co-expression network analysis (WGCNA), gene trend analysis, and correlation analysis suggest that PSY1 and ZDS16 may be important players in the synthesis of carotenoids during goji fruit ripening. Meanwhile, 63 transcription factors (TFs) were identified related to goji fruit carotenoid biosynthesis. Among them, four TFs (CMB1-1, WRKY22-1, WRKY22-3, and RAP2-13-like) may have potential regulatory relationships with PSY1 and ZDS16. This work sheds light on the molecular network of carotenoid synthesis and explains the differences in carotenoid accumulation in different colored goji fruits.

6.
ACS Appl Mater Interfaces ; 15(31): 37640-37648, 2023 Aug 09.
Article En | MEDLINE | ID: mdl-37491709

As a new-generation photoelectric material, perovskites have attracted researchers' attention due to their excellent optoelectronic properties. However, the existence of defects inevitably causes structural degradation and restricts their performance, which need to be further improved by post-treatment. At present, post-treatments mostly focus on non-contact treatments, which may constrain the effect since the influence on the perovskites caused by the direct contact is much more straightly. Therefore, we proposed an annealing strategy of straight manipulation in a solvent atmosphere with the assistance of polyimide (PI) tape for the perovskite post-treatment, due to the high heat resistance and less glue residual of this tape. It casts an influence on the perovskite directly, proving the possibility of the straight manipulation by operators, promoting the recrystallization of the perovskite grains and removing the impurity substance. The optimized Pb-free perovskite film exhibits a better X-ray sensitivity of 7.5 × 104 µC Gyair-1 cm-2 and a great detection limit of 47 nGyair s-1, which is comparable to advanced Pb-based perovskite X-ray detectors and all commercial ones. The new annealing strategy provides a facile, effective, and simple method to improve the perovskite quality, exhibiting the potential and harmlessness of the direct contact post-treatment, which paves the way for a broader application of perovskites.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 591-595, 2023 May.
Article Zh | MEDLINE | ID: mdl-37248589

Objective: To analyze the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in the physical examination population, to establish a risk prediction model for the occurrence of MAFLD, and to provide management strategies for the prevention and occurrence of the disease. Methods: A total of 14664 people who underwent physical examination at the Physical Examination Center, West China Hospital, Sichuan University between January 2018 and December 2021 were selected as research subjects. The subjects were divided into a MAFLD group ( n=4013) and a non-MAFLD group ( n=10651) according to whether they had MAFLD. The differences in biochemical indices, for example, glycolipid metabolism levels, were compared and logistic regression was conducted to analyze the risk factors for MAFLD, thereby establishing a nomogram prediction model. The prediction effect of the model was validated and evaluated with the consistency index (C-index) and the calibration curve. Results: Among the 14664 subjects who underwent physical examination, 4013 were MAFLD patients, presenting an overall prevalence of 27.37%, with significantly higher prevalence in men than that in women (38.99% vs. 10.06%, P<0.001). Compared with those of the non-MAFLD group, the levels of glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and uric acid (UA) were increased ( P<0.05), while the high density lipoprotein cholesterol (HDL-C) level was decreased ( P<0.05) in the MAFLD group. The results of logistic regression analysis showed that male sex, age, body mass index, GLU, TG and hypertension were all independent risk factors of MAFLD, while HDL-C was a protective factor of MAFLD. The risk factors were used to establish a nomogram risk prediction model and the C-index and calibration curve showed that the nomogram model produced good predictive performance. The receiver operating characteristic (ROC) curve showed that the nomogram model had good predictive value for the risk of MAFLD. Conclusion: We found a relatively high prevalence of MAFLD in the physical examination population, and the nomogram model established with routine physical examination screening can provide indications for the clinical screening and analysis of high-risk patients, which has an early warning effect on the high-risk population.


Non-alcoholic Fatty Liver Disease , Humans , Male , Female , Risk Factors , Triglycerides , Cholesterol, HDL , Physical Examination , Glucose
8.
Adv Sci (Weinh) ; 10(23): e2300256, 2023 Aug.
Article En | MEDLINE | ID: mdl-37232232

Lead halide perovskites have made remarkable progress in the field of radiation detection owing to the excellent and unique optoelectronic properties. However, the instability and the toxicity of lead-based perovskites have greatly hindered its practical applications. Alternatively, lead-free perovskites with high stability and environmental friendliness thus have fascinated significant research attention for direct X-ray detection. In this review, the current research progress of X-ray detectors based on lead-free halide perovskites is focused. First, the synthesis methods of lead-free perovskites including single crystals and films are discussed. In addition, the properties of these materials and the detectors, which can provide a better understanding and designing satisfactory devices are also presented. Finally, the challenge and outlook for developing high-performance lead-free perovskite X-ray detectors are also provided.

9.
Curr Issues Mol Biol ; 44(12): 5933-5948, 2022 Nov 28.
Article En | MEDLINE | ID: mdl-36547065

Plant−water relations mediated by aquaporins (AQPs) play vital roles in both key plant growth processes and responses to environmental challenges. As a well-known medicinal and edible plant, the harsh natural growth habitat endows Lycium plants with ideal materials for stress biology research. However, the details of their molecular switch for water transport remain unclear. In the present work, we first identified and characterized AQP family genes from Lycium (L.) barbarum at the genome scale and conducted systemic bioinformatics and expression analyses. The results showed that there were 38 Lycium barbarum AQPs (LbAQPs) in L. barbarum, which were classified into four subfamilies, including 17 LbPIP, 9 LbTIP, 10 LbNIP, and 2 LbXIP. Their encoded genes were unevenly distributed on all 12 chromosomes, except chromosome 10. Three of these genes encoded truncated proteins and three genes underwent clear gene duplication events. Cis-acting element analysis indicated that the expression of LbAQPs may be mainly regulated by biotic/abiotic stress, phytohormones and light. The qRT-PCR assay indicated that this family of genes presented a clear tissue-specific expression pattern, in which most of the genes had maximal transcript levels in roots, stems, and leaves, while there were relatively lower levels in flowers and fruits. Most of the LbAQP genes were downregulated during L. barbarum fruit ripening and presented a negative correlation with the fruit relative water content (RWC). Most of their transcripts presented a quick and sharp upregulation response to heat stress following exposure of the 2-month-old seedlings to a 42 °C temperature for 0, 1, 3, 12, or 24 h. Our results proposed that LbAQPs were involved in L. barbarum key development events and abiotic stress responses, which may lay a foundation for further studying the molecular mechanism of the water relationship of Lycium plants, especially in harsh environments.

10.
ACS Nano ; 16(7): 10199-10208, 2022 Jul 26.
Article En | MEDLINE | ID: mdl-35622531

Pb-free perovskite material is considered to be a promising material utilized in next-generation X-ray detectors due to its high X-ray absorption coefficient, decent carrier transport properties, and relatively low toxicity. However, the pixelation of the perovskite material with an industry-level photolithography processing method remains challenging due to its poor structural stability. Herein, we use Cs2AgBiBr6 perovskite material as the prototype and investigate its interaction with photolithographic polar solvents. Inspired by that, we propose a wafer-scale photolithography patterning method, where the pixeled perovskite array devices for X-ray detection are successfully prepared. The devices based on pixeled Pb-free perovskite material show a high detection sensitivity up to 19118 ± 763 µC Gyair-1 cm-2, which is comparable to devices with Pb-based perovskite materials and superior to the detection sensitivity (∼20 µC Gyair-1 cm-2) of the commercial a-Se detector. After pixelation, the devices achieve an improved spatial resolution capacity with the spatial frequency from 2.7 to 7.8 lp mm-1 at modulation-transfer-function (MTF) = 0.2. Thus, this work may contribute to the development of high-performance array X-ray detectors based on Cs2AgBiBr6 perovskite material.

11.
Arch Microbiol ; 204(3): 197, 2022 Feb 26.
Article En | MEDLINE | ID: mdl-35217917

Lycium barbarum L. is a well-known traditional geoherb in Ningxia, China. The fruits of L. barbarum contain several dietary constituents, and thus, they exert many beneficial effects on human health. However, a few studies have been conducted on the geoherb L. barbarum and its rhizosphere soil fungal community. In this study, we determined the physicochemical properties and fungal community structure of rhizosphere soil of L. barbarum from three regions of China, namely Ningxia (NX), Qinghai (QH), and Xinjiang (XJ), during three development stages of L. barbarum. Soil pH varied between 7.56 and 8.60 across the three regions, indicating that alkaline soil is conducive to the growth of L. barbarum. The majority of soil properties in NX, an authentic geoherb-producing area, were substantially inferior to those in XJ and QH during all three developmental stages. Total sugar, polysaccharide (LBP), and flavonoid contents were the highest in wolfberry fruits from NX. High-throughput sequencing showed that the abundance of the soil fungal population in NX was higher than that in QH and XJ during the flowering and fruiting stage and summer dormant stage. Moreover, the soil fungal diversity increased with the development of wolfberry. Ascomycota and Mortierellomycota were the predominant phyla in the rhizosphere fungal communities in all samples. Redundancy analysis showed a significant correlation of the soil-available phosphorus and LBP of wolfberry fruits with the fungal community composition. The characteristics of rhizosphere fungal communities determined in the present study provide insights into the mechanism of geoherb formation in NX wolfberry.


Lycium , Mycobiome , Humans , Lycium/chemistry , Polysaccharides , Rhizosphere , Soil , Soil Microbiology
12.
Commun Biol ; 4(1): 671, 2021 06 03.
Article En | MEDLINE | ID: mdl-34083720

Wolfberry Lycium, an economically important genus of the Solanaceae family, contains approximately 80 species and shows a fragmented distribution pattern among the Northern and Southern Hemispheres. Although several herbaceous species of Solanaceae have been subjected to genome sequencing, thus far, no genome sequences of woody representatives have been available. Here, we sequenced the genomes of 13 perennial woody species of Lycium, with a focus on Lycium barbarum. Integration with other genomes provides clear evidence supporting a whole-genome triplication (WGT) event shared by all hitherto sequenced solanaceous plants, which occurred shortly after the divergence of Solanaceae and Convolvulaceae. We identified new gene families and gene family expansions and contractions that first appeared in Solanaceae. Based on the identification of self-incompatibility related-gene families, we inferred that hybridization hotspots are enriched for genes that might be functioning in gametophytic self-incompatibility pathways in wolfberry. Extremely low expression of LOCULE NUBER (LC) and COLORLESS NON-RIPENING (CNR) orthologous genes during Lycium fruit development and ripening processes suggests functional diversification of these two genes between Lycium and tomato. The existence of additional flowering locus C-like MADS-box genes might correlate with the perennial flowering cycle of Lycium. Differential gene expression involved in the lignin biosynthetic pathway between Lycium and tomato likely illustrates woody and herbaceous differentiation. We also provide evidence that Lycium migrated from Africa into Asia, and subsequently from Asia into North America. Our results provide functional insights into Solanaceae origins, evolution and diversification.


Chromosomes, Plant/genetics , Genome, Plant/genetics , Lycium/genetics , Solanaceae/genetics , Whole Genome Sequencing/methods , Africa , Asia , Evolution, Molecular , Fruit/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Geography , Lycium/classification , Lycium/metabolism , North America , Phylogeny , Polyploidy , Polysaccharides/metabolism , Solanaceae/classification , Solanaceae/metabolism , Species Specificity
13.
Nanomicro Lett ; 13(1): 51, 2021 Jan 05.
Article En | MEDLINE | ID: mdl-34138239

In human-machine interaction, robotic hands are useful in many scenarios. To operate robotic hands via gestures instead of handles will greatly improve the convenience and intuition of human-machine interaction. Here, we present a magnetic array assisted sliding triboelectric sensor for achieving a real-time gesture interaction between a human hand and robotic hand. With a finger's traction movement of flexion or extension, the sensor can induce positive/negative pulse signals. Through counting the pulses in unit time, the degree, speed, and direction of finger motion can be judged in real-time. The magnetic array plays an important role in generating the quantifiable pulses. The designed two parts of magnetic array can transform sliding motion into contact-separation and constrain the sliding pathway, respectively, thus improve the durability, low speed signal amplitude, and stability of the system. This direct quantization approach and optimization of wearable gesture sensor provide a new strategy for achieving a natural, intuitive, and real-time human-robotic interaction.

14.
Sci Rep ; 10(1): 14656, 2020 09 04.
Article En | MEDLINE | ID: mdl-32887902

Goji (Lycium barbarum L.) is a highly medicinal value tree species. The yield and nutritional contents of goji fruit are significant affected by fertilizer level. In this study, we analyzed the yield and nutritional contents change of goji fruit, which planted in pot (vermiculite:perlite, 1:2, v:v) in growth chamber under P0 (32.5 g/per tree), P1 (65 g/per tree), and P2 (97.5 g/per tree). Meanwhile, we utilized an integrated Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) to analysis of the response of the metabolome in goji fruit to phosphorus level. The results show that the yield of goji fruits had strongly negative correlation with phosphorus level, especially in the third harvest time. The amino acids, flavonoids, polysaccharides, and betaine contents of goji fruits in the first harvest time had obvious correlated with the level of phosphorus level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the impact of different phosphorus fertilizer levels on each group mainly involved the biosynthesis of flavonoids. The results provide new insights into the theoretical basis of the relationship between the nutritional contents of goji fruits and phosphorus fertilizer level.


Fertilizers/analysis , Fruit/chemistry , Fruit/metabolism , Lycium/chemistry , Lycium/metabolism , Metabolome , Phosphorus/metabolism , Amino Acids/metabolism , Betaine/metabolism , Chromatography, High Pressure Liquid , Flavonoids/metabolism , Metabolomics/methods , Polysaccharides/metabolism , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry
15.
Diabetes Metab Syndr Obes ; 13: 2533-2540, 2020.
Article En | MEDLINE | ID: mdl-32765032

BACKGROUND: Thyroid dysfunction is associated with diabetes, but it is unclear if the thyroid hormone levels change in euthyroid adults with diabetes. OBJECTIVE: To investigate the association between thyroid hormone levels and diabetes in euthyroid adults. METHODS: Among the euthyroid adults who underwent health examination in West China Hospital of Sichuan University in 2016, patients with diabetes were identified according to the medical history, fasting blood glucose and HbA1c. Age and sex matched controls were identified from the population. The patients with diabetes group was further divided into two subgroups: patients with newly diagnosed diabetes (NDD) and with previously diagnosed diabetes (PDD). Independent t-test and multivariate logistic regression models were used to investigate the difference in the levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and the ratio of FT4/FT3 between groups. RESULTS: We included 32,557 participants, 2,271 with diabetes. Compared to the adults without diabetes, the odds ratios (ORs) per one unit elevation of TSH, FT4, FT4/FT3 ratio and FT3 in patients with diabetes were 0.88 [95% confidence interval (CI): 0.82-0.95], 1.11 (95% CI: 1.08-1.14), 2.05 (95% CI: 1.81-2.32) and 0.85 (95% CI: 0.78-0.93), respectively. Compared to the NDD group, the ORs per one unit elevation of TSH, FT4, FT4/FT3 ratio and FT3 of the PDD group were 0.81 (95% CI: 0.71-0.92), 1.08 (95% CI: 1.04-1.12), 1.76 (95% CI: 1.49-2.08) and 1.01 (95% CI: 0.92-1.12), respectively. CONCLUSION: In euthyroid adults, diabetes was associated with increased FT4/FT3 ratio, which is linked to the peripheral turnover of the thyroid hormones.

16.
Nat Chem Biol ; 16(7): 766-775, 2020 07.
Article En | MEDLINE | ID: mdl-32483376

Cell surfaces are glycosylated in various ways with high heterogeneity, which usually leads to ambiguous conclusions about glycan-involved biological functions. Here, we describe a two-step chemoenzymatic approach for N-glycan-subtype-selective editing on the surface of living cells that consists of a first 'delete' step to remove heterogeneous N-glycoforms of a certain subclass and a second 'insert' step to assemble a well-defined N-glycan back onto the pretreated glyco-sites. Such glyco-edited cells, carrying more homogeneous oligosaccharide structures, could enable precise understanding of carbohydrate-mediated functions. In particular, N-glycan-subtype-selective remodeling and imaging with different monosaccharide motifs at the non-reducing end were successfully achieved. Using a combination of the expression system of the Lec4 CHO cell line and this two-step glycan-editing approach, opioid receptor delta 1 (OPRD1) was investigated to correlate its glycostructures with the biological functions of receptor dimerization, agonist-induced signaling and internalization.


Cell Membrane/chemistry , Epithelial Cells/chemistry , Glycoconjugates/chemistry , Oligosaccharides/chemistry , Receptors, Opioid, delta/chemistry , Animals , CHO Cells , Cell Line, Tumor , Cell Membrane/metabolism , Colforsin/pharmacology , Cricetulus , Enkephalin, Leucine/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Gene Expression , Glycoconjugates/metabolism , Glycosylation , HEK293 Cells , Humans , Mice , Oligosaccharides/metabolism , Protein Multimerization/drug effects , Protein Transport/drug effects , Receptors, Opioid, delta/genetics , Receptors, Opioid, delta/metabolism , Transgenes
17.
Bioorg Chem ; 94: 103391, 2020 01.
Article En | MEDLINE | ID: mdl-31761409

Thermostability of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), as a critical property of biotherapeutics, is important for their physicochemical processes, pharmacodynamics, and pharmacokinetics. Fc glycosylation of mAbs plays a crucial role in antibody functions including thermostability, however, due to the lack of homogeneous glycosylation for comparison, the precise impact of glycoforms on thermostability of mAbs and ADCs remains challenging to elucidate. In this paper, we employed the technique of differential scanning fluorimetry (DSF) to investigate the thermostability of Fc domains, glycoengineered mAbs, and ADCs, carrying well-defined N-glycan structures for comparison. The results revealed that high-mannose-type N-glycans dramatically reduce the Tm value of Fc, compared to complex-type N-glycans. We also found that core-fucose contributes to the thermostability of mAbs, and the unnatural modification on non-reducing end of biantennary N-glycan can compensate the reduced stability of afucosylated mAbs and maintain the advantage of enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). DSF analysis of lysine-linked and glycosite-specific ADCs indicated that thermostability of glycan-linked ADCs is reduced, but it could be improved by using an optimized linkage. This work provides an in-depth analysis on thermostability of mAbs and ADCs with homogeneous glycoforms, and also proposes new strategies for optimizing glycoengineered mAbs and glycosite-specific ADCs using unnatural glycan and stabilized linkage.


Antibodies, Monoclonal/analysis , Fluorometry , Immunoconjugates/analysis , Temperature , Antibodies, Monoclonal/immunology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Glycosylation , Humans , Immunoconjugates/immunology , Molecular Structure , Structure-Activity Relationship
18.
Molecules ; 24(21)2019 Oct 28.
Article En | MEDLINE | ID: mdl-31661883

The yield and quality of goji (Lycium barbarum L.) fruit are heavily dependent on fertilizer, especially the availability of nitrogen, phosphorus, and potassium (N, P, and K, respectively). In this study, we performed a metabolomic analysis of the response of goji berry to nitrogen fertilizer levels using an Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) method. There was no significant difference in the fruit yield or the commodity grade between N0 (42.5 g/plant), N1 (85 g/plant), and N2 (127.5 g/plant). The primary nutrients of the goji berry changed with an increasing nitrogen fertilization. Comparative metabolomic profiling of three nitrogen levels resulted in the identification of 612 metabolites, including amino acids, flavonoids, carbohydrates, organic acids, and lipids/alcohols, among others, of which 53 metabolites (lipids, fatty acids, organic acids, and phenolamides) demonstrated significant changes. These results provide new insights into the molecular mechanisms of the relationship between yield and quality of goji berry and nitrogen fertilizer.


Fertilizers , Fruit/metabolism , Lycium/metabolism , Metabolomics , Antioxidants/chemistry , Chromatography, High Pressure Liquid , Fruit/drug effects , Lycium/drug effects , Nitrogen/pharmacology , Plant Extracts/metabolism , Tandem Mass Spectrometry
19.
Clin Chim Acta ; 492: 57-61, 2019 May.
Article En | MEDLINE | ID: mdl-30738955

BACKGROUND: A sigma-metric run size nomogram is used to recommend quality control (QC) strategies to reduce patient risks. Herein, we aimed to evaluate the sigma performance of 8 enzymes and apply multistage bracketed statistical QC (SQC). METHODS: Sigma performance of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), amylase (AMY), and lipase (LIP) were determined. Daily workload of each test was estimated and expected reporting QC intervals were designed. Per the nomogram, "start-up" and "monitor" QC rules were determined from sigma performance. SQC was finally applied, followed by quality improvement. RESULTS: Sigma metrics were as follows: 5.26 (ALT), 4.80(AST), 5.25(GGT), 3.36(ALP), 4.71(LDH), 15.45(CK), 10.77(AMY), and 3.70 (LIP). "Start-up" rules were MR N2, MR N4, MR N2, MR N4, MR N4, 1:2.5 s N1, 1:3 s N1, and MR N4, and "monitor" QC rules were 1:2.5 s N1, 1:3 s N2, 1:2.5 s N1, MR N4, 1:3 s N2, 1:3 s N1, 1:3 s N1, MR N2 for 8 enzymes, respectively. CONCLUSION: Multistage bracketed SQC is determined by sigma performance. Risk monitoring is significant during assaying to reduce patient risks and improve quality.


Enzyme Assays/statistics & numerical data , Enzymes/metabolism , Nomograms , Quality Control
20.
Angew Chem Int Ed Engl ; 57(27): 8154-8158, 2018 07 02.
Article En | MEDLINE | ID: mdl-29737628

Oxynitrides are promising visible-light-responsive photocatalysts, but their structures are almost confined with three-dimensional (3D) structures such as perovskites. A phase-pure Li2 LaTa2 O6 N with a layered perovskite structure was successfully prepared by thermal ammonolysis of a lithium-rich oxide precursor. Li2 LaTa2 O6 N exhibited high crystallinity and visible-light absorption up to 500 nm. As opposed to well-known 3D oxynitride perovskites, Li2 LaTa2 O6 N supported by a binuclear RuII complex was capable of stably and selectively converting CO2 into formate under visible light (λ>400 nm). Transient absorption spectroscopy indicated that, as compared to 3D oxynitrides, Li2 LaTa2 O6 N possesses a lower density of mid-gap states that work as recombination centers of photogenerated electron/hole pairs, but a higher density of reactive electrons, which is responsible for the higher photocatalytic performance of this layered oxynitride.

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