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1.
Int J Biol Macromol ; 270(Pt 1): 132056, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704070

RESUMO

Since the potential carcinogenic, toxic and non-degradable dyes trigger serious environmental contamination by improper treatment, developing novel adsorbents remains a major challenge. A novel high efficiency and biopolymer-based environmental-friendly adsorbent, chitosan­sodium tripolyphosphate-melamine sponge (CTS-STPP-MS) composite, was prepared for Orange II removing with chitosan as raw material, sodium tripolyphosphate as cross-linking agent. The composite was carefully characterized by SEM, EDS, FT-IR and XPS. The influence of crosslinking conditions, dosage, pH, initial concentration, contacting time and temperature on adsorption were tested through batch adsorption experiments. CTS-STPP-MS adsorption process was exothermic, spontaneous and agreed with Sips isotherm model accompanying the maximum adsorption capacity as 948 mg∙g-1 (pH = 3). Notably, the adsorption performance was outstanding for high concentration solutions, with a removal rate of 97 % in up to 2000 mg∙L-1 OII solution (100 mg sorbent dosage, 50 mL OII solution, pH = 3, 289.15 K). In addition, the adsorption efficiency yet remained 97.85 % after 5 repeated adsorption-desorption cycles. The driving force of adsorption was attributed to electrostatic attraction and hydrogen bonds which was proved by adsorption results coupled with XPS. Owing to the excellent properties of high-effective, environmental-friendly, easy to separate and regenerable, CTS-STPP-MS composite turned out to be a promising adsorbent in contamination treatment.

2.
J Transl Med ; 22(1): 360, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632606

RESUMO

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.


Assuntos
Agmatina , Microbioma Gastrointestinal , Hipertensão , Pré-Eclâmpsia , Complicações na Gravidez , Feminino , Gravidez , Humanos , Microbioma Gastrointestinal/genética , Reprodutibilidade dos Testes , Fezes/microbiologia , Metaboloma , Inflamação , Bactérias , RNA Ribossômico 16S
3.
Cell Commun Signal ; 22(1): 235, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643161

RESUMO

BACKGROUND: Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. METHODS: Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients. RESULTS: Two probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. CONCLUSIONS: GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.


Assuntos
Infertilidade Feminina , Camundongos , Animais , Feminino , Humanos , Infertilidade Feminina/metabolismo , Folículo Ovariano/metabolismo , Oócitos/química , Oócitos/metabolismo , Células da Granulosa/metabolismo , Estrogênios/metabolismo , Fator 9 de Diferenciação de Crescimento/genética , Fator 9 de Diferenciação de Crescimento/análise , Fator 9 de Diferenciação de Crescimento/metabolismo
4.
Cell Mol Life Sci ; 81(1): 174, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597936

RESUMO

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.


Assuntos
Infertilidade Masculina , Motilidade dos Espermatozoides , Masculino , Animais , Camundongos , Humanos , Motilidade dos Espermatozoides/genética , Sêmen , Infertilidade Masculina/genética , Cabeça do Espermatozoide , Espermatozoides
5.
Biochem Pharmacol ; : 116205, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615918

RESUMO

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous studies find that nitazoxanide and its metabolite tizoxanide affect AMPK, STAT3, and Smad2/3 signals which are involved in the pathogenesis of liver fibrosis, therefore, in the present study, we examined the effect of nitazoxanide on experimental liver fibrosis and elucidated the potential mechanisms. The in vivo experiment results showed that oral nitazoxanide (75, 100 mg·kg-1) significantly improved CCl4- and bile duct ligation-induced liver fibrosis in mice. Oral nitazoxanide activated the inhibited AMPK and inhibited the activated STAT3 in liver tissues from liver fibrosis mice. The in vitro experiment results showed that nitazoxanide and its metabolite tizoxanide activated AMPK and inhibited STAT3 signals in LX-2 cells (human hepatic stellate cells). Nitazoxanide and tizoxanide inhibited cell proliferation and collagen I expression and secretion of LX-2 cells. Nitazoxanide and tizoxanide inhibited transforming growth factor-ß1 (TGF-ß1)- and IL-6-induced increases of cell proliferation, collagen I expression and secretion, inhibited TGF-ß1- and IL-6-induced STAT3 and Smad2/3 activation in LX-2 cells. In mouse primary hepatic stellate cells, nitazoxanide and tizoxanide also activated AMPK, inhibited STAT3 and Smad2/3 activation, inhibited cell proliferation, collagen I expression and secretion. In conclusion, nitazoxanide inhibits liver fibrosis and the underlying mechanisms involve AMPK activation, and STAT3 and Smad2/3 inhibition.

6.
Nat Nanotechnol ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491184

RESUMO

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.

7.
Materials (Basel) ; 17(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38541517

RESUMO

Ultra-thick offshore steel, known for its high strength, high toughness, and corrosion resistance, is commonly used in marine platforms and ship components. However, when offshore steel is in service for an extended period under conditions of high pressure, extreme cold, and high-frequency impact loads, the weld joints are prone to fatigue failure or even fractures. Addressing these issues, this study designed a narrow-gap laser wire filling welding process and successfully welded a 100-mm new type of ultra-thick offshore steel. Using finite element simulation, EBSD testing, SEM analysis, and impact experiments, this study investigates the weld's microstructure, impact toughness, and fracture mechanisms. The research found that at -80 °C, the welded joint exhibited good impact toughness (>80 J), with the impact absorption energy on the surface of the weld being 217.7 J, similar to that of the base material (225.3 J), and the fracture mechanism was primarily a ductile fracture. The impact absorption energy in the core of the weld was 103.7 J, with the fracture mechanism mainly being a brittle fracture. The EBSD results indicated that due to the influence of the welding thermal cycle and the cooling effect of the narrow-gap process, the grains gradually coarsened from the surface of the welded plate to the core of the weld, which was the main reason for the decreased impact toughness at the joint core. This study demonstrates the feasibility of using narrow-gap laser wire filling welding for 100-mm new type ultra-thick offshore steel and provides a new approach for the joining of ultra-thick steel plates.

9.
J Biol Eng ; 18(1): 19, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414057

RESUMO

BACKGROUND: Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current "gold standard" treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 µg/kg) to test its biological activity. RESULTS: An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines. CONCLUSION: The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.

10.
Environ Sci Pollut Res Int ; 31(11): 16642-16652, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38319416

RESUMO

The resource utilization of agricultural and forestry waste, especially the high-value transformation of low-grade phosphate rock and derivatives, is an important way to achieve sustainable development. This study focuses on the impregnation and co-pyrolysis of rice straw (RS) with fused calcium magnesium phosphate (FMP), FMP modified with citric acid (CA-FMP), and calcium dihydrogen phosphate (MCP) to produce three phosphorous-enriched biochars (PBC). The Cd(II) removal efficiency of biochars before and after phosphorus modification was investigated, along with the adsorption mechanism and contribution of biochars modified with different phosphorus sources to Cd(II) adsorption. The result indicated that CA-FMP and MCP could be more uniformly loaded onto biochar, effectively increasing the specific surface area (SSA) and total pore volume. The adsorption of Cd(II) onto PBC followed a mono-layer chemisorption process accompanied by intraparticle diffusion. The adsorption of Cd(II) by PBC involved ion exchange, mineral precipitation, complexation with oxygen-containing functional groups (OFGs), cation-π interaction, electrostatic interaction, and physical adsorption. Ion exchange was identified as the primary adsorption mechanism for Cd(II) by BC and FBC (51.53% and 53.15% respectively), while mineral precipitation played a major role in the adsorption of Cd(II) by CBC and MBC (51.10% and 47.98% respectively). Moreover, CBC and MBC significantly enhanced the adsorption capacity of Cd(II), with maximum adsorption amounts of 128.1 and 111.5 mg g-1 respectively.


Assuntos
Cádmio , Poluentes Químicos da Água , Cádmio/análise , Fósforo , Adsorção , Minerais , Carvão Vegetal , Fosfatos , Cálcio
11.
Sci Rep ; 14(1): 4550, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402305

RESUMO

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.


Assuntos
Hipotireoidismo , Parabenos , Ratos , Animais , Humanos , Parabenos/toxicidade , Parabenos/química , Hormônios Tireóideos , Hipotireoidismo/induzido quimicamente , Tiroxina , Tireotropina
12.
BMC Pregnancy Childbirth ; 24(1): 126, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347456

RESUMO

Chimerism results from the fusion of two zygotes in a single embryo, whereas mosaicism results from mitotic errors in a single zygote. True human chimerism is rare, with fewer than 100 cases reported in the literature. Here, we report a case in which the fetus was identified as having tetragametic chimerism based on short tandem repeat - polymerase chain reaction analysis of the family observed during amniocentesis for advanced maternal age. The chimerism occurred via the fertilization of two ova by two spermatozoa, followed by the fusion of early embryos. The genotypes of the two amniotic fluid samples obtained successively by one puncture were completely different, and the sex chromosomes were XY. Karyotyping and copy number variation sequencing showed no abnormalities. The fetus was delivered at term and the phenotype of the newborn was normal.


Assuntos
Quimerismo , Variações do Número de Cópias de DNA , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Amniocentese , Cariotipagem , Fenótipo
13.
Sci Total Environ ; 918: 170579, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38336061

RESUMO

It is inevitable for NO to be involved in the soot combustion in diesel particulate filters (DPFs), so giving full play to the NO oxidation activity is one of the most effective means to improve the DPF regeneration performance. In this work, based on the results of programmed temperature oxidation (TPO) experiments, Fourier transfer inference spectroscopy, and X-ray photoelectron spectroscopy, the evolution of surface functional groups was seriously analyzed to explore the soot oxidation mechanism. The results revealed that with the presence of NO in the air atmosphere, the concentration of -ONO2 groups showed an increasing trend in the early oxidation stage of 0-20 % oxidation degree (OD) and then slowly decreased during 20-80 % OD, while the variations in CH functional group concentration were directly related to the concentration NO in the air atmosphere. COO functional group is easy to decompose, and NO promotes COO's generation and decomposition. The sp3/sp2 hybrid ratio is strongly correlated with CO (carbon­oxygen double bond), but the content of CO is also affected by the desorption of COO functional groups. It is worth noting that when the soot oxidation degree is at 50 %-80 % OD, CO groups are converted to CO functional groups.

14.
AMB Express ; 14(1): 6, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38196027

RESUMO

The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6-8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.

15.
Poult Sci ; 103(3): 103376, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228059

RESUMO

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.


Assuntos
Galinhas , Estudo de Associação Genômica Ampla , Animais , Galinhas/genética , Estudo de Associação Genômica Ampla/veterinária , Genômica , Fenótipo , Sorogrupo
16.
bioRxiv ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38260393

RESUMO

Current SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+ T cell activation, however CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine platform, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific HR2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naïve mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular immune responses in human cells. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities. The programmability of this platform underscores its potential utility in addressing future pandemics.

17.
Andrology ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273709

RESUMO

BACKGROUND: The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood. OBJECTIVES: To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs). MATERIALS AND METHODS: First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p-mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p-eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot. RESULTS: The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p-mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone. DISCUSSION AND CONCLUSION: HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function.

18.
J Org Chem ; 89(3): 1753-1761, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38252457

RESUMO

A novel and flexible domino reaction of aurones with pyridin-2-yl active methylene compounds promoted by I2/BF3 has been developed to afford spirodihydroindolizines and indolizines in a controllable manner. When the reaction was performed in 1,2-dichloroethane at 80 °C, a variety of spirodihydroindolizines were obtained, whereas it almost exclusively provided a series of indolizines when the reaction was performed in a mixed solvent of 1,2-dichloroethane and N,N-dimethylformamide at a relatively higher temperature of 100 °C. Being metal-free, excellent product selectivity, high atom economy, good functional group tolerance, and feasibility for large-scale synthesis are the salient features of the developed methodology.

19.
Int J Biol Macromol ; 257(Pt 1): 128615, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070798

RESUMO

Nowadays, highly toxic antimony has severely posed threat to water sources and jeopardized human health. Fabricating adsorbents with the capability of easy separation, high efficiency and large adsorption capacity remains a major challenge. In this paper, zirconium functionalized chitosan melamine foam (ZCMF) was fabricated with zirconium and chitosan crosslinked onto melamine foam, then utilized for the removal of antimony(III/V) in water. The characterization of SEM and EDS collectively showed that ZCMF has a porous structure which could boost the mass transfer rate and zirconium ions on the surface could provide plentiful active adsorption sites. Systematic adsorption experiments demonstrated that the experimental data of Sb(III) and Sb(V) were consistent with the pseudo-second-order and Elovich kinetic models, respectively, and the Langmuir maximum adsorption capacities were separately 255.35 mg g-1 (Sb(III)) and 414.41 mg g-1 (Sb(V)), which displayed prominent performance among adsorbents derived from biomass. Combining the XPS and FTIR characterization with experimental data, it is rational to speculate that ZCMF could remove Sb from aqueous solution through ligand exchange, electrostatic attraction, and surface complexation mechanisms. ZCMF exhibited excellent performance, including large adsorption capacity, easy separation, facile preparation and eco-friendliness. It could be a promising new adsorbent for the treatment of antimony-containing wastewater.


Assuntos
Quitosana , Triazinas , Poluentes Químicos da Água , Humanos , Antimônio/química , Zircônio/química , Água , Adsorção , Poluentes Químicos da Água/química , Cinética
20.
Ginekol Pol ; 95(2): 132-142, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37743645

RESUMO

OBJECTIVES: To research the associations between fructose-bisphosphate aldolase B (ALDOB) gene polymorphisms and intrahepatic cholestasis of pregnancy (ICP) risk. MATERIAL AND METHODS: Whole-genome sequencing (WGS) was performed to detect ALDOB polymorphisms. Five web-available tools were employed to predict the effect of the site variant on the protein. Protein structure comparisons between the reference and ALDOB-modified samples were performed by SWISS-MODEL and Chimera 1.14rc, respectively. RESULTS: We identified 28 genetic variants in the ALDOB gene. When the cut-off value of minor allele frequency (MAF) of loci was 0.001 in four databases, five missense variants, including rs747604233, rs759204107, rs758242037, rs371526091 and rs77718928, were reserved for subsequent analysis. These variants were absent from the 1029 control individuals. The influence of all five variants on protein function was predicted to be damaging by the abovementioned five prediction software programs. Bioinformatics analysis demonstrated that these five missense variants were highly conserved among vertebrates. Compared to the wild-type protein structure, all five mutated protein structures showed a slight change in the chemical bond lengths of the enzyme activity domains. The combined clinical data indicate that the variant group had a significantly older age (p = 0.038), a higher level of indirect bilirubin (IDBIL, p = 0.033), and lower counts of white blood cells (WBCs, p = 7.38E-05) and platelets (PLTs, p = 0.018) than the wild-type group. CONCLUSIONS: This is the first study to examine the associations between ALDOB polymorphisms and ICP disease in 249 Chinese patients with ICP. Our present study expands the understanding of the pathogenesis of ICP.


Assuntos
Colestase Intra-Hepática , Complicações na Gravidez , Animais , Feminino , Humanos , Gravidez , China , Colestase Intra-Hepática/genética , Frutose-Bifosfato Aldolase/genética , Frequência do Gene , Polimorfismo de Nucleotídeo Único , Complicações na Gravidez/genética
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