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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 273-278, 2024 Apr 18.
Article in Chinese | MEDLINE | ID: mdl-38595244

ABSTRACT

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.


Subject(s)
Hydroxychloroquine , Lupus Erythematosus, Systemic , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Immunosuppressive Agents/therapeutic use , Severity of Illness Index
2.
Natl Sci Rev ; 11(4): nwae042, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38487497

ABSTRACT

Tracking the dynamic surface evolution of metal halide perovskite is crucial for understanding the corresponding fundamental principles of photoelectric properties and intrinsic instability. However, due to the volatility elements and soft lattice nature of perovskites, several important dynamic behaviors remain unclear. Here, an ultra-high vacuum (UHV) interconnection system integrated by surface-sensitive probing techniques has been developed to investigate the freshly cleaved surface of CH3NH3PbBr3  in situ under given energy stimulation. On this basis, the detailed three-step chemical decomposition pathway of perovskites has been clarified. Meanwhile, the evolution of crystal structure from cubic phase to tetragonal phase on the perovskite surface has been revealed under energy stimulation. Accompanied by chemical composition and crystal structure evolution, electronic structure changes including energy level position, hole effective mass, and Rashba splitting have also been accurately determined. These findings provide a clear perspective on the physical origin of optoelectronic properties and the decomposition mechanism of perovskites.

3.
Reprod Biomed Online ; 48(4): 103727, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38402677

ABSTRACT

RESEARCH QUESTION: Does type 1 diabetes mellitus (T1DM) affect reproductive health of female patients? What is the potential mechanism of reproductive dysfunction in female patients caused by T1DM? DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level. RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways. CONCLUSION: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.


Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans , Humans , Female , Animals , Mice , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/pathology , Mice, Inbred NOD , Pancreas/metabolism , Pancreas/pathology , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Cytokines/metabolism , Inflammation/metabolism
4.
Reprod Sci ; 31(6): 1719-1731, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38396297

ABSTRACT

Diabetes is known to negatively affect male reproduction. Recent clinical results have confirmed that mesenchymal stem cell (MSC)-based therapies are safe and effective for the treatment of diabetes. However, the effect and potential mechanism through which MSC transplantation improves diabetes-derived male reproductive dysfunction are still unknown. In the present study, we first established a male T1D mouse model through intraperitoneal injection of streptozotocin for five consecutive days. Subsequently, we evaluated the blood glucose levels, fertility, and histology and immunology of the pancreas, testes, and penis of T1D mice with or without transplantation of menstrual blood-derived endometrial stem cells (MenSCs) or umbilical cord mesenchymal stem cells (UCMSCs). Glucose was added to the medium in which the Leydig cells were cultured to imitate high glucose-injured cell viability. Subsequently, we evaluated the cellular viability, ROS levels, and mitochondrial membrane potential of Leydig cells treated with or without MenSC-conditioned medium (MenSC-CM) using a CCK8 assay, immunofluorescence, and flow cytometry. The targeted proteins are involved in the potential mechanism underlying MenSC-derived improvements, which was further validated via Western blotting. Collectively, our results indicated that MenSC transplantation significantly ameliorated reproductive dysfunction in male T1D mice by enhancing cellular antioxidative capacity and promoting angiogenesis. This study provides solid evidence and support for the application of MSCs to improve diabetes-induced male reproductive dysfunction.


Subject(s)
Diabetes Mellitus, Experimental , Endometrium , Animals , Male , Mice , Diabetes Mellitus, Experimental/therapy , Female , Endometrium/metabolism , Endometrium/pathology , Leydig Cells/metabolism , Antioxidants/pharmacology , Infertility, Male/therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/therapy , Mesenchymal Stem Cell Transplantation/methods , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL
5.
Microorganisms ; 11(12)2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38137995

ABSTRACT

As one of the environmental factors that seriously affect plant growth and crop production, drought requires an efficient but environmentally neutral approach to mitigate its harm to plants. Soil microbiomes can interact with plants and soil to improve the adverse effects of drought. Medicago ruthenica (L.) is an excellent legume forage with strong drought tolerance, but the key role of microbes in fighting drought stress remains unclear. What kind of flora plays a key role? Is the recruitment of such flora related to its genotype? Therefore, we selected three varieties of M. ruthenica (L.) for drought treatment, analyzed their growth and development as well as their physiological and biochemical characteristics, and performed 16S rRNA high-throughput sequencing analysis on their rhizosphere soils to clarify the variety-mediated response of rhizosphere bacteria to drought stress. It was found that among the three varieties of M. ruthenica (L.), Mengnong No.2, Mengnong No.1 and Zhilixing were subjected to drought stress and showed a reduction in plant height increment of 24.86%, 34.37%, and 31.97% and in fresh weight of 39.19%, 50.22%, and 41.12%, respectively, whereas dry weight was reduced by 23.26%, 26.10%, and 24.49%, respectively. At the same time, we found that the rhizosphere microbial community of Mengnong No. 2 was also less affected by drought, and it was able to maintain the diversity of rhizosphere soil microflora stable after drought stress, while Mennong No. 1 and Zhilixing were affected by drought stress, resulting in a decrease in rhizosphere soil bacterial community diversity indices to 92.92% and 82.27%, respectively. Moreover, the rhizosphere of Mengnon No. 2 was enriched with more nitrogen-fixing bacteria Rhizobium than the other two varieties of M. ruthenica (L.), which made it still have a good ability to accumulate aboveground biomass after drought stress. In conclusion, this study proves that the enrichment process of bacteria is closely related to plant genotype, and different varieties enrich different types of bacteria in the rhizosphere to help them adapt to drought stress, and the respective effects are quite different. Our results provide new evidence for the study of bacteria to improve the tolerance of plants to drought stress and lay a foundation for the screening and study mechanism of drought-tolerant bacteria in the future.

6.
Stem Cell Reports ; 18(12): 2418-2433, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37995703

ABSTRACT

Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Neural Stem Cells , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Neurons/metabolism , Neural Stem Cells/metabolism , Cell Differentiation , Olfactory Bulb/metabolism , Neurogenesis/physiology
7.
BMC Genomics ; 24(1): 658, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37919673

ABSTRACT

BACKGROUND: Wolfberry is rich in carotenoids, flavonoids, vitamins, alkaloids, betaines and other bioactive ingredients. For over 2,000 years, wolfberry has been used in China as a medicinal and edible plant resource. Nevertheless, the content of bioactive ingredients varies by cultivars, resulting in uneven quality across wolfberry cultivars and species. To date, research has revealed little about the underlying molecular mechanism of the metabolism of flavonoids, carotenoids, and other bioactive ingredients in wolfberry. RESULTS: In this context, the transcriptomes of the Lycium barbarum L. cultivar 'Ningqi No. 1' and Lycium chinense Miller were compared during the fruit maturity stage using the Illumina NovaSeq 6000 sequencing platform, and subsequently, the changes of the gene expression profiles in two types of wolfberries were analysed. In total, 256,228,924 clean reads were obtained, and 8817 differentially expressed genes (DEGs) were identified, then assembled by Basic Local Alignment Search Tool (BLAST) similarity searches and annotated using Gene Ontology (GO), Clusters of Orthologous Groups of proteins (KOG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). By combining these transcriptome data with data from the PubMed database, 36 DEGs related to the metabolism of bioactive ingredients and implicated in the metabolic pathway of carotenoids, flavonoids, terpenoids, alkaloids, vitamins, etc., were identified. In addition, among the 9 differentially expressed transcription factors, LbAPL, LbPHL11 and LbKAN4 have raised concerns. The protein physicochemical properties, structure prediction and phylogenetic analysis indicated that LbAPL and LbPHL11 may be good candidate genes involved in regulating the flavonoid metabolism pathway in wolfberry. CONCLUSIONS: This study provides preliminary evidence for the differences in bioactive ingredient content at the transcription level among different wolfberry species, as well as a research and theoretical basis for the screening, cloning and functional analysis of key genes involved in the metabolism of bioactive ingredients in wolfberry.


Subject(s)
Alkaloids , Lycium , Lycium/genetics , Phylogeny , Flavonoids , Metabolic Networks and Pathways/genetics , Carotenoids/metabolism , Vitamins/metabolism
8.
Sheng Wu Gong Cheng Xue Bao ; 39(7): 3015-3036, 2023 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-37584145

ABSTRACT

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.


Subject(s)
Lycium , Transcriptome , Flavonoids/metabolism , Fruit/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Lycium/genetics , Lycium/metabolism , Metabolic Networks and Pathways
9.
Front Mol Neurosci ; 16: 1191324, 2023.
Article in English | MEDLINE | ID: mdl-37415834

ABSTRACT

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disease caused by CAG repeats in exon 1 of the HTT gene. A hallmark of HD along with other psychiatric and neurodegenerative diseases is alteration in the neuronal circuitry and synaptic loss. Microglia and peripheral innate immune activation have been reported in pre-symptomatic HD patients; however, what "activation" signifies for microglial and immune function in HD and how it impacts synaptic health remains unclear. In this study we sought to fill these gaps by capturing immune phenotypes and functional activation states of microglia and peripheral immunity in the R6/2 model of HD at pre-symptomatic, symptomatic and end stages of disease. These included characterizations of microglial phenotypes at single cell resolution, morphology, aberrant functions such as surveillance and phagocytosis and their impact on synaptic loss in vitro and ex vivo in R6/2 mouse brain tissue slices. To further understand how relevant the observed aberrant microglial behaviors are to human disease, transcriptomic analysis was performed using HD patient nuclear sequencing data and functional assessments were conducted using induced pluripotent stem cell (iPSC)-derived microglia. Our results show temporal changes in brain infiltration of peripheral lymphoid and myeloid cells, increases in microglial activation markers and phagocytic functions at the pre-symptomatic stages of disease. Increases in microglial surveillance and synaptic uptake parallel significant reduction of spine density in R6/2 mice. These findings were mirrored by an upregulation of gene signatures in the endocytic and migratory pathways in disease-associated microglial subsets in human HD brains, as well as increased phagocytic and migratory functions of iPSC-derived HD microglia. These results collectively suggest that targeting key and specific microglial functions related to synaptic surveillance and pruning may be therapeutically beneficial in attenuating cognitive decline and psychiatric aspects of HD.

10.
EMBO J ; 42(11): e110384, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37083045

ABSTRACT

Most adult hippocampal neural stem cells (NSCs) remain quiescent, with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger the transition from quiescence to activation are still poorly understood. Here, we found the activity of the transcriptional co-activator Yap1 to be enriched in active NSCs. Genetic deletion of Yap1 led to a significant reduction in the relative proportion of active NSCs, supporting a physiological role of Yap1 in regulating the transition from quiescence to activation. Overexpression of wild-type Yap1 in adult NSCs did not induce NSC activation, suggesting tight upstream control mechanisms, but overexpression of a gain-of-function mutant (Yap1-5SA) elicited cell cycle entry in NSCs and hilar astrocytes. Consistent with a role of Yap1 in NSC activation, single cell RNA sequencing revealed a partial induction of an activated NSC gene expression program. Furthermore, Yap1-5SA expression also induced expression of Taz and other key components of the Yap/Taz regulon that were previously identified in glioblastoma stem cell-like cells. Consequently, dysregulated Yap1 activity led to repression of hippocampal neurogenesis, aberrant cell differentiation, and partial acquisition of a glioblastoma stem cell-like signature.


Subject(s)
Glioblastoma , Neural Stem Cells , Adult , Humans , Glioblastoma/metabolism , Cell Differentiation/physiology , Hippocampus/metabolism , Neurogenesis/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Neural Stem Cells/metabolism
11.
Front Microbiol ; 14: 1114400, 2023.
Article in English | MEDLINE | ID: mdl-36910228

ABSTRACT

Drought is a major abiotic stress that threatens crop production. Soil microbiomes are thought to play a role in enhancing plant adaptation to various stresses. However, it remains unclear whether soil microbiomes play a key role when plants are challenged by drought and whether different varieties are enriched with specific bacteria at the rhizosphere. In this study, we measured changes in growth phenotypes, physiological and biochemical characteristics of drought-tolerant alfalfa (AH) and drought-sensitive (QS) under sterilized and unsterilized soil conditions with adequate watering and with drought stress, and analyzed the rhizosphere bacterial community composition and changes using 16S rRNA high-throughput sequencing. We observed that the unsterilized treatment significantly improved the growth, and physiological and biochemical characteristics of alfalfa seedlings under drought stress compared to the sterilized treatment. Under drought stress, the fresh and dry weight of seedlings increased by 35.24, 29.04, and 11.64%, 2.74% for unsterilized AH and QS, respectively, compared to sterilized treatments. The improvement was greater for AH than for QS. AH and QS recruited different rhizosphere bacteria when challenged by drought. Interestingly, under well-watered conditions, the AH rhizosphere was already rich in drought-tolerant bacterial communities, mainly Proteobacteria and Bacteroidetes, whereas these bacteria started to increase only when QS was subjected to drought. When drought stress was applied, AH was enriched with more drought-tolerant bacteria, mainly Acidobacteria, while the enrichment was weaker in QS rhizosphere. Therefore, the increase in drought tolerance of the drought-tolerant variety AH was greater than that of the drought-sensitive variety QS. Overall, this study confirmed the key role of drought-induced rhizosphere bacteria in improving the adaptation of alfalfa to drought stress, and clarified that this process is significantly related to the variety (genotype). The results of this study provide a basis for improving drought tolerance in alfalfa by regulating the rhizosphere microbiome.

12.
Adv Mater ; 35(7): e2207172, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36401565

ABSTRACT

Although CsPbI3 perovskites have shown tremendous potential in the photovoltaic field owing to their excellent thermal stability, the device performance is seriously restricted by severe photovoltage loss. The buried titanium oxide/perovskite interface plays a critical role in interfacial charge transport and perovskite crystallization, which is closely related to open-circuit voltage deficit stemming from nonradiative recombination. Herein, target molecules named 3-sulphonatopropyl acrylate potassium salts are deliberately employed with special functional groups for modifying the buried interface, giving rise to favorable functions in terms of passivating interfacial defects, optimizing energetic alignment, and facilitating perovskite crystallization. Experimental characterizations and theoretical calculations reveal that the buried interface modification inhibits the electron transfer barrier and simultaneously improves perovskite crystal quality, thereby reducing trap-assisted charge recombination and interfacial energetic loss. Consequently, the omnibearing modification regarding the buried interface endows the devices with an impressive efficiency of 20.98%, achieving a record-low VOC deficit of 0.451 V. The as-proposed buried interface modification strategy renders with a universal prescription to push the limit of VOC deficit, showing a promising future in developing high-performance all-inorganic perovskite photovoltaics.

13.
Front Plant Sci ; 14: 1324333, 2023.
Article in English | MEDLINE | ID: mdl-38179479

ABSTRACT

Soil salinization is a global environmental issue and a significant abiotic stress that threatens crop production. Root-associated rhizosphere microbiota play a pivotal role in enhancing plant tolerance to abiotic stresses. However, limited information is available concerning the specific variations in rhizosphere microbiota driven by different plant genotypes (varieties) in response to varying levels of salinity stress. In this study, we compared the growth performance of three alfalfa varieties with varying salt tolerance levels in soils with different degrees of salinization. High-throughput 16S rRNA and ITS sequencing were employed to analyze the rhizosphere microbial communities. Undoubtedly, the increasing salinity significantly inhibited alfalfa growth and reduced rhizosphere microbial diversity. However, intriguingly, salt-tolerant varieties exhibited relatively lower susceptibility to salinity, maintaining more stable rhizosphere bacterial community structure, whereas the reverse was observed for salt-sensitive varieties. Bacillus emerged as the dominant species in alfalfa's adaptation to salinity stress, constituting 21.20% of the shared bacterial genera among the three varieties. The higher abundance of Bacillus, Ensifer, and Pseudomonas in the rhizosphere of salt-tolerant alfalfa varieties is crucial in determining their elevated salt tolerance. As salinity levels increased, salt-sensitive varieties gradually accumulated a substantial population of pathogenic fungi, such as Fusarium and Rhizoctonia. Furthermore, rhizosphere bacteria of salt-tolerant varieties exhibited increased activity in various metabolic pathways, including biosynthesis of secondary metabolites, carbon metabolism, and biosynthesis of amino acids. It is suggested that salt-tolerant alfalfa varieties can provide more carbon sources to the rhizosphere, enriching more effective plant growth-promoting bacteria (PGPB) such as Pseudomonas to mitigate salinity stress. In conclusion, our results highlight the variety-mediated enrichment of rhizosphere microbiota in response to salinity stress, confirming that the high-abundance enrichment of specific dominant rhizosphere microbes and their vital roles play a significant role in conferring high salt adaptability to these varieties.

14.
Front Plant Sci ; 13: 995031, 2022.
Article in English | MEDLINE | ID: mdl-36531350

ABSTRACT

High-quality alfalfa is an indispensable resource for animal husbandry and sustainable development. Its nutritional quality changes dramatically during its life cycle and, at present, no molecular mechanisms for nutrient metabolic variation in alfalfa leaves at different growth stages have been clearly reported. We have used correlation and network analyses of the alfalfa leaf metabolome, proteome, and transcriptome to explore chlorophyll, flavonoid, and amino acid content at two development stages: budding stage (BS) and full-bloom stage (FBS). A high correlation between the expression of biosynthetic genes and their metabolites revealed significant reductions in metabolite content as the plant matured from BS to FBS. l-Glutamate, the first molecule of chlorophyll biosynthesis, decreased, and the expression of HemA, which controls the transformation of glutamyl-tRNA to glutamate 1-semialdehyde, was down-regulated, leading to a reduction in leaf chlorophyll content. Flavonoids also decreased, driven at least in part by increased expression of the gene encoding CYP75B1: flavonoid 3'-monooxygenase, which catalyzes the hydroxylation of dihydroflavonols and flavonols, resulting in degradation of flavonoids. Expression of NITRILASE 2 (NIT2) and Methyltransferase B (metB), which regulate amino acid metabolism and influence the expression of genes of the glycolysis-TCA pathway, were down-regulated, causing amino acid content in alfalfa leaves to decrease at FBS. This study provides new insights into the complex regulatory network governing the content and decrease of chlorophyll, amino acids, flavonoids, and other nutrients in alfalfa leaves during maturation. These results further provide a theoretical basis for the generation of alfalfa varieties exhibiting higher nutritional quality, high-yield cultivation, and a timely harvest.

15.
Lupus Sci Med ; 9(1)2022 11.
Article in English | MEDLINE | ID: mdl-36351697

ABSTRACT

OBJECTIVE: Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC). METHODS: Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared. RESULTS: Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027). CONCLUSIONS: SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.


Subject(s)
Immunosuppressive Agents , Lupus Erythematosus, Systemic , Humans , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Cyclophosphamide/adverse effects , Glucocorticoids
16.
Appl Opt ; 61(13): 3566-3578, 2022 May 01.
Article in English | MEDLINE | ID: mdl-36256394

ABSTRACT

For large ground-based telescopes, static and dynamic disturbances would greatly degrade the optical performance. This is especially true for wide field survey telescopes with prime focus optics. The estimation of disturbance effects on large telescopes is becoming increasingly important during the design phase. Therefore, a wide field survey telescope with 2.5 m aperture and 3.5 deg field of view is studied in this research. This telescope is under construction now, and its first light is expected at the beginning of 2023. The estimation method for the optical performance under static and dynamic disturbances in the temporal domain and the active compensation method to improve the optical alignment, are investigated, which is a supplement for the simulation in the frequency domain. First, based on the mechanical model, the optical misalignment is established, where the deviation of the primary mirror is obtained from the length gauges and the deviation of the corrector is computed using the fitting method. Second, a method for compensating the static and dynamic disturbances is proposed, improving the optical performance. This method uses the disturbed primary mirror as the reference, and the corrector is actively controlled to align with it. Finally, a series of experimental tests and numerical simulations is conducted. The results show that the mechanical modeling error is within 10% and the maximum optical misalignment is reduced from 12''/0.27 to 0.2''/0.006mm for static disturbance and from 1.3''/0.03 to 0.4''/0.01mm for dynamic disturbance. Through active compensation, the telescope optical property is greatly improved. The modeling method and the simulation process mentioned in this research can also be used in the other relevant fields.

17.
Placenta ; 124: 18-27, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35597169

ABSTRACT

INTRODUCTION: Preeclampsia, a specific complication of pregnancy, is a leading cause of perinatal and maternal mortality worldwide. N6-methyladenosine (m6A) is a prevalent and reversible modification of mammalian mRNAs, and is known to play an important role in various physiological and pathological processes. However, little is known about its possible effects on trophoblasts in preeclampsia. METHODS: Colorimetric RNA m6A methylation quantification assay and dot blotting were used to assess the levels of global RNA m6A modification in placental tissues collected from females with normal pregnancy and preeclampsia, while the mRNA levels of major m6A methyltransferases/demethylases were investigated by quantitative real-time polymerase chain reaction. The effects of methyltransferase-like 14 (METTL14) on trophoblasts were evaluated using cell counting kit-8, transwell invasion assay, autophagic flux assay, and Annexin V/propidium iodide apoptosis assay. The molecular mechanism underlying the regulation of forkhead box O3a (FOXO3a) expression by METTL14 was determined using methylated RNA immunoprecipitation and transcription inhibition assays. RESULTS: Global RNA m6A methylation and METTL14 expression were significantly increased in placental tissues obtained from patients with preeclampsia. In vitro studies showed that overexpression of METTL14 in HTR-8/SVneo cells inhibited trophoblast proliferation and invasion, but induced trophoblast autophagy and apoptosis. We further demonstrated that METTL14 epigenetically elevated FOXO3a expression via an m6A-dependent mechanism. FOXO3a inhibition effectively prevented the impairment of trophoblast proliferation and invasion, and diminished the induction of trophoblast autophagy and apoptosis in METTL14-overexpressing HTR-8/SVneo cells. DISCUSSION: Increased METTL14-mediated m6A modification results in an adverse impact on trophoblast function by elevating FOXO3a expression.


Subject(s)
Methyltransferases , Pre-Eclampsia , Trophoblasts , Cell Line , Cell Movement , Female , Forkhead Box Protein O3/biosynthesis , Forkhead Box Protein O3/genetics , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Placenta/metabolism , Placenta/pathology , Pre-Eclampsia/enzymology , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Trophoblasts/metabolism , Trophoblasts/pathology , Up-Regulation
18.
Materials (Basel) ; 15(4)2022 Feb 11.
Article in English | MEDLINE | ID: mdl-35207882

ABSTRACT

To improve the mechanical performance and lower the production cost of magnesium oxysulfate cement (MOSC), this article investigates the effects of single and compounded addition of metakaolin (MK) and/or fly ash (FA) on the setting time, mechanical strength, water resistance, hydration product, composition, and microstructure of the resulting cement. MOSC samples with different proportions, ranging from 0 to 30 wt.%, of FA and/or MK substituting magnesium oxide (MgO) were prepared. The microstructure was explored by scanning electron microscopy, X-ray diffraction, and mercury intrusion porosimetry. The findings suggest that adding FA can delay the setting of MOSC; however, the effect of adding MK to MOSC was reversed. Furthermore, the phase composition of the MOSC hydration products was unaltered upon adding FA and/or MK, but thicker and longer 517 phase crystals were observed. FA and MK can effectively fill the large pores of MOSC through filling and nucleation effects, reduce the pore size, and form a denser microstructure, thereby improving its mechanical properties. The optimal MOSC sample was found by substituting 10 wt.% of both FA and MK, resulting in a cement that exhibited a short setting time and an incredibly high mechanical strength and density. These findings will further the development of stronger, more cost-efficient, and more water-resistant MOSC products.

19.
Nano Lett ; 22(4): 1467-1474, 2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35133160

ABSTRACT

Fundamental understanding of ion migration inside perovskites is of vital importance for commercial advancements of photovoltaics. However, the mechanism for external ions incorporation and its effect on ion migration remains elusive. Herein, taking K+ and Cs+ co-incorporated mixed halide perovskites as a model, the impact of external ions on ion migration behavior has been interpreted via multiple dimensional characterization aspects. The space-effect on phase segregation inhibition has been revealed by the photoluminescence evolution and in situ dynamic cathodoluminescence behaviors. The plane-effect on current suppression along grain boundary has been evidenced via visualized surface current mapping, local current hysteresis, and time-resolved current decay. And the point-effect on activation energy incremental for individual ions has been also probed by cryogenic electronic quantification. All these results sufficiently demonstrate the passivated ion migration results in the eventually improved phase stability of perovskite, of which the origin lies in various ion migration energy barriers.

20.
Adv Mater ; 34(14): e2109998, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35112404

ABSTRACT

Rubidium cation (Rb+ ) addition is witnessed to play a pivotal role in boosting the comprehensive performance of organic-inorganic hybrid perovskite solar cells. However, the origin of such success derived from irreplaceable superiorities brought by Rb+ remains ambiguous. Herein, grain-boundary-including atomic models are adopted for the accurate theoretical analysis of practical Rb+ distribution in perovskite structures. The spatial distribution, covering both the grain interiors and boundaries, is thoroughly identified by virtue of synchrotron-based grazing-incidence X-ray diffraction. On this basis, the prominent elevation of the halogen vacancy formation energy, improved charge-carrier dynamics, and the electronic passivation mechanism in the grain interior are expounded. As evidenced by the increased energy barrier and suppressed microcurrent, the critical role of Rb+ addition in blocking the diffusion pathway along grain boundaries, inhibiting halide phase segregation, and eventually enhancing intrinsic stability is elucidated. Hence, the linkage avalanche effect of occupied location dominated by subtle changes in Rb+ concentration on electronic defects, ion migration, and phase stability is completely investigated in detail, shedding a new light on the advancement of high-efficiency cascade-incorporating strategies and perovskite compositional engineering.

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