RESUMEN
Inorganic lanthanide nanomaterials as photoluminescent biolabels have attracted increasing attention due to their superior physicochemical properties. However, unstable conjugation of inorganic lanthanide nanomaterials with biological function units (such as antibodies) induces instability of conjugated complexes in aqueous solution, limiting their clinical application. In this study, we developed a rapid point-of-care testing (POCT) platform strategy based on coordination-enhanced time-resolved luminescence of specially nanostructural lanthanide particles for lateral flow immunoassay (CE-TRFIA). This strategy integrates a nanoprobe via a dendritic mesoporous silica nanosphere (DMSN) loading a large amount of ultrasmall amorphous europium oxide (Eu2O3) nanoparticles, which rapidly dissolve to release Eu3+ cations under neutral pH value and form luminescent complexes with photosensitizers (such as ß-NTA and TOPO) in an LFIA system. This innovative strategy achieves high-sensitivity detection and long-term stability primarily through high-loading probes, excellent dissolution enhancement, stable covalent coupling, and time-resolved detection. With Procalcitonin (PCT) antigen selected as the detection sample, this approach achieves high-sensitivity detection of PCT with a limit of detection (LoD) as low as 1.9 pg/mL, significantly lower than that of commercial LFIA (0.1 ng/mL), and excellent clinical correlation (r = 0.989). The method offers chemiluminescence-level sensitivity without the need for large instruments while retaining the real-time detection characteristics of LFIA. Our results highlight CE-TRFIA as a highly sensitive, specific, and rapid POCT solution for detecting low-abundance biomarkers such as PCT, enhancing the diagnostic capabilities of traditional LFIA and offering significant potential for ultrasensitive and rapid clinical diagnostics.
RESUMEN
Methods: Sugammadex vials were fractionated into 25, 50, or 100 mg aliquots, which would be distributed to anesthesia staff by pharmacy staff in approximate 2 mg/kg of actual body weight doses (±10%). We analyzed changes in sugammadex waste and dosing practices 1/1/2019 to 3/15/2023 pre/postintervention (4/1/2021). We gauged dose appropriateness using last train of four (TOF) prior to sugammadex administration. Results: 7,889 patients 2-17 years (4,771 with documented TOF), ASA 1-4 receiving general anesthesia with a steroidal NMB medication and sugammadex reversal. Pre- and postintervention mean doses were 2.5 mg/kg (SD: 1.2) and 2.4 mg/kg (SD: 0.96), respectively. A smaller proportion of cases received standard 2 or 4 mg/kg doses (pre: 77.6 vs. post: 66.7%). Mean waste per case declined from 4.2 mg/kg (SD: 4.1) to 0.22 mg/kg (SD: 0.38). Among cases with 0 or 1 measured twitches on TOF that should receive at least 4 mg/kg, fewer received at least 3.6 mg/kg (post: 56.7% vs. pre: 66.8%), and a greater proportion received less than 2.2 mg/kg (post: 27.4% vs. pre: 20.7%). Among cases that should have received at least 2 mg/kg by TOF, the proportion of patients receiving more than 3.6 mg/kg declined from 9.5% to 5.2%. Discussion. Fractionating sugammadex vials was associated with decreases in waste, but not dose, and significant underdosing was more likely to occur. While vial fractionation could enable increased access to sugammadex and other costly medications, it may introduce unintended consequences.
RESUMEN
In order to ensure the filling integrity of complex counter-gravity casting and improve metallurgical quality, it is necessary to shorten the filling time while avoiding air entrainments. To address this contradiction, a novel nonlinear pressurization method was proposed in this study. Through systematically analyzing the relationship between critical gating velocity and stable filling height, a criterion for iterative calculation of nonlinear pressurization curve was established, and an empirical expression between nonlinear pressurizing speed and the filling height was obtained. Based on the empirical expression, a nonlinear pressurization curve can be designed according to the casting structures and initial pressurizing speeds. The above nonlinear pressure curve design method was validated through water filling experiments. It was proved that the nonlinear pressure curve can shorten the filling time while avoiding air entrainments. It provides important processing control method for improving the low-pressure casting performance of complex castings.
RESUMEN
Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in infants and the most frequent adverse outcome of premature birth, despite major efforts to minimize injury. It is thought to result from aberrant repair response triggered by either prenatal or recurrent postnatal injury to the lungs during development. Intrauterine inflammation is an important risk factor for prenatal lung injury, which is also increasingly linked to BPD. However, the specific mechanisms remain unclear. This review summarizes clinical and animal research linking intrauterine inflammation to BPD. We assess how intrauterine inflammation affects lung alveolarization and vascular development. In addition, we discuss prenatal therapeutic strategies targeting intrauterine inflammation to prevent or treat BPD.
Asunto(s)
Displasia Broncopulmonar , Inflamación , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/patología , Humanos , Animales , Inflamación/patología , Femenino , Embarazo , Pulmón/patología , Feto , Recién NacidoRESUMEN
Seed vigor is a complex trait encompassing seed germination, seedling emergence, growth, seed longevity, and stress tolerance, all are crucial for direct seeding in rice. Here, we report that the AP2/ERF transcription factor OsRAV1 (RELATED TO ABI3 AND VP1) positively regulates seed germination, vigor, and salt tolerance. Additionally, OsRAV1 was differently expressed in embryo and endosperm, with the OsRAV1 localized in the nucleus. Transcriptomic analysis revealed that OsRAV1 modulates seed vigor through plant hormone signal transduction and phenylpropanoid biosynthesis during germination. Haplotype analysis showed that rice varieties carrying Hap3 displayed enhanced salt tolerance during seed germination. These findings suggest that OsRAV1 is a potential target in breeding rice varieties with high seed vigor suitable for direct seeding cultivation.
RESUMEN
Inherited retinal degenerations (IRDs) are a group of genetic disorders characterized by the progressive degeneration of retinal cells, leading to irreversible vision loss. SLC4A7 has emerged as a candidate gene associated with IRDs, yet its mechanisms remain largely unknown. This study aims to investigate the role of slc4a7 in retinal development and its associated molecular pathogenesis in zebrafish. Morpholino oligonucleotide knockdown, CRISPR/Cas9 genome editing, quantitative RT-PCR, eye morphometric measurements, immunofluorescent staining, TUNEL assays, visual motor responses, optokinetic responses, rescue experiments, and bulk RNA sequencing were used to assess the impact of slc4a7 deficiency on retinal development. Our results demonstrated that the knockdown of slc4a7 resulted in a dose-dependent reduction in eye axial length, ocular area, and eye-to-body-length ratio. The fluorescence observations showed a significant decrease in immunofluorescence signals from photoreceptors and in mCherry fluorescence from RPE in slc4a7-silenced morphants. TUNEL staining uncovered the extensive apoptosis of retinal cells induced by slc4a7 knockdown. Visual behaviors were significantly impaired in the slc4a7-deficient larvae. GO and KEGG pathway analyses reveal that differentially expressed genes are predominantly linked to aspects of vision, ion channels, and phototransduction. This study demonstrates that the loss of slc4a7 in larvae led to profound visual impairments, providing additional insights into the genetic mechanisms predisposing individuals to IRDs caused by SLC4A7 deficiency.
Asunto(s)
Retina , Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Retina/metabolismo , Retina/patología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Técnicas de Silenciamiento del Gen , Regulación del Desarrollo de la Expresión Génica , Apoptosis/genética , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Degeneración Retiniana/metabolismo , Larva/crecimiento & desarrollo , Larva/metabolismo , Larva/genéticaRESUMEN
Chiral carbon nanodots (CNDs) were fabricated through the hydrothermal processing of sulfanilic acid and chiral tartaric acid, exhibiting outstanding catalytic performance for the chiral catalysis of the ring-opening reaction. Furthermore, the catalytic mechanism was proposed to understand the link between the chiral structure and the performance of the catalyst.
RESUMEN
BACKGROUND: The outcomes of older patients are significantly limited by hospitalization-associated disability (HAD), and there are currently few available management options for HAD. This review aimed to identify and quantify the risk factors for HAD, to provide reliable evidence for developing a HAD prevention program centered on risk factor management among older patients. METHODS: The MEDLINE, Embase, PsycINFO, CINAHL, and PubMed databases were searched in March 2024 to identify cross-sectional and cohort studies that used multivariable analysis to examine risk factors for HAD among older patients. RESULTS: We screened 883 studies, 21 of which met our inclusion criteria. Our findings revealed a substantial association between various risk factors and HAD among older patients. Specifically, advanced age, female sex, Caucasian ethnicity, comorbidity burden, better activities of daily living at admission, dementia diagnosis, and longer lengths of stay were significant risk factors for HAD. Furthermore, frailty, poor physical function, immobility, and delirium were identified as confirmed risk factors for HAD among older patients. CONCLUSIONS: This review provided a comprehensive synthesis of available evidence on risk factors for HAD among older patients, serving as a valuable guide for the development of HAD prevention strategies both prior to and during hospitalization.
Asunto(s)
Hospitalización , Humanos , Hospitalización/estadística & datos numéricos , Factores de Riesgo , Anciano , Personas con Discapacidad/estadística & datos numéricos , Femenino , Masculino , Actividades Cotidianas , Anciano de 80 o más AñosRESUMEN
In modern agriculture, Controlled environment agriculture (CEA) stands out as a contemporary production mode that leverages precise control over environmental conditions such as nutrient, temperature, light, and other factors to achieve efficient and high-quality agricultural production. Numerous studies have demonstrated the efficacy of manipulating these environmental factors in the short period before harvest to enhance crop yield and quality in CEA. This comprehensive review aims to provide insight into various pre-harvest practices employed in CEA, including nutrient deprivation, nutrient supply, manipulation of the light environment, and the application of exogenous hormones, with the objective of improving yield and quality in horticultural crops. Additionally, we propose an intelligent pre-harvest management system to cultivate high-quality horticultural crops. This system integrates sensor technology, data analysis, and intelligent control, enabling the customization of specific pre-harvest strategies based on producers' requirements. The envisioned pre-harvest intelligent system holds the potential to enhance crop quality, increase yield, reduce resource wastage, and offer innovative ideas and technical support for the sustainable development of CEA.
RESUMEN
Engineering enzyme-substrate binding pockets is the most efficient approach for modifying catalytic activity, but is limited if the substrate binding sites are indistinct. Here, we developed a 3D convolutional neural network for predicting protein-ligand binding sites. The network was integrated by DenseNet, UNet, and self-attention for extracting features and recovering sample size. We attempted to enlarge the dataset by data augmentation, and the model achieved success rates of 48.4%, 35.5%, and 43.6% at a precision of ≥50% and 52%, 47.6%, and 58.1%. The distance of predicted and real center is ≤4 Å, which is based on SC6K, COACH420, and BU48 validation datasets. The substrate binding sites of Klebsiella variicola acid phosphatase (KvAP) and Bacillus anthracis proline 4-hydroxylase (BaP4H) were predicted using DUnet, showing high competitive performance of 53.8% and 56% of the predicted binding sites that critically affected the catalysis of KvAP and BaP4H. Virtual saturation mutagenesis was applied based on the predicted binding sites of KvAP, and the top-ranked 10 single mutations contributed to stronger enzyme-substrate binding varied while the predicted sites were different. The advantage of DUnet for predicting key residues responsible for enzyme activity further promoted the success rate of virtual mutagenesis. This study highlighted the significance of correctly predicting key binding sites for enzyme engineering.
Asunto(s)
Aprendizaje Automático , Sitios de Unión , Ingeniería de Proteínas/métodos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fosfatasa Ácida/química , Fosfatasa Ácida/genética , Fosfatasa Ácida/metabolismo , Especificidad por Sustrato , Bacillus anthracis/genética , Bacillus anthracis/enzimología , Klebsiella/genética , Klebsiella/enzimología , Ligandos , Unión Proteica , Modelos Moleculares , Redes Neurales de la ComputaciónRESUMEN
Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients' physical and mental health. Schwann cells (SCs) are the major glial cells of the peripheral nervous system, which play an important role in various inflammatory and metabolic neuropathies by providing nutritional support, wrapping axons and promoting repair and regeneration. Increasingly, high glucose (HG) has been found to promote the progression of DPN pathogenesis by targeting SCs death regulation, thus revealing the specific molecular process of programmed cell death (PCD) in which SCs are disrupted is an important link to gain insight into the pathogenesis of DPN. This paper is the first to review the recent progress of HG studies on apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis pathways in SCs, and points out the crosstalk between various PCDs and the related therapeutic perspectives, with the aim of providing new perspectives for a deeper understanding of the mechanisms of DPN and the exploration of effective therapeutic targets.
Asunto(s)
Neuropatías Diabéticas , Células de Schwann , Células de Schwann/metabolismo , Células de Schwann/patología , Humanos , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Animales , Apoptosis , Muerte Celular , Autofagia/fisiología , Necroptosis/fisiologíaRESUMEN
Collagen II (COL2) is the major component of cartilage tissue and is widely applied in pharmaceuticals, food, and cosmetics. In this study, COL fragments were extracted from human COL2 for secretory expression in Pichia pastoris. Three variants were successfully secreted by shake flask cultivation with a yield of 73.3-100.7 mg/L. The three COL2 variants were shown to self-assemble into triple-helix at 4 °C and capable of forming higher order assembly of nanofiber and hydrogel. The bioactivities of the COL2 variants were validated, showing that sample 205 exhibited the best performance for inducing fibroblast differentiation and cell migration. Meanwhile, sample 205 and 209 exhibited higher capacity for inducing in vitro blood clotting than commercial mouse COL1. To overexpress sample 205, the expression cassettes were constructed with different promoters and signal peptides, and the fermentation condition was optimized, obtaining a yield of 172 mg/L for sample 205. Fed-batch fermentation was carried out using a 5 L bioreactor, and the secretory protease Pep4 was knocked out to avoid sample degradation, finally obtaining a yield of 3.04 g/L. Here, a bioactive COL2 fragment was successfully identified and can be overexpressed in P. pastoris; the variant may become a potential biomaterial for skin care.
Asunto(s)
Colágeno Tipo II , Humanos , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Ratones , Animales , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/biosíntesis , Fermentación , Pichia/genética , Pichia/metabolismo , Movimiento Celular/genética , Fibroblastos/metabolismo , Diferenciación Celular , Reactores Biológicos , Saccharomycetales/genética , Saccharomycetales/metabolismo , Nanofibras/químicaRESUMEN
BACKGROUND: Sugammadex is a neuromuscular blockade (NMB) reversal agent introduced in the United States in 2016, which allows the reversal of deep NMB, not possible with neostigmine. Few data describe associated practice changes, if any, in NMB medication use that may have resulted from its availability. We hypothesized that after institutional introduction, use of NMB agents increased. Furthermore, as NMB medication is typically used when the airway has been secured with an endotracheal tube (ETT), we speculated that ETT use may have also increased over the same time period as a result of sugammadex availability. METHODS: This was a single-center cross-sectional study of patients ages 2 to 17 years undergoing general anesthesia for surgical cases where anesthesia providers often have discretion over NMB medication use or whether to use an ETT versus a laryngeal mask airway (LMA), comparing the time periods 2014 to 2016 (presugammadex) to 2017 to 2019 (early sugammadex) and 2020 to 2022 (established sugammadex). Outcomes included use of (1) any nondepolarizing NMB medication during the case and (2) an ETT versus LMA. We used generalized linear mixed models to examine changes in practice patterns over time. We also examined whether patient age group and in-room provider (resident versus certified registered nurse anesthetist [CRNA]) were associated with increased NMB medication or ETT use. RESULTS: There were 25,638 eligible anesthetics. Patient and surgical characteristics were similar across time periods. In adjusted analyses, the odds of NMB medication use increased from 2017 to 2019 (odds ratio [OR], 1.55, 95% confidence interval [CI], 1.38-1.75) and 2020 to 2022 (OR, 5.62, 95% CI, 4.96-6.37) relative to 2014 to 2016, and were higher in older children (age 6-11 years vs 2-5 years OR, 1.81, 95% CI, 1.63-2.01; age 12-17 years vs 2-5 years OR, 7.01, 95% CI, 6.19-7.92) and when the primary in-room provider was a resident rather than a CRNA (OR, 1.24, 95% CI, 1.12-1.37). The odds of ETT use declined 2017 to 2019 (OR, 0.69, 95% CI, 0.63-0.75) and 2020 to 2022 (OR, 0.71, 95% CI, 0.65-0.78), more so in older children (age 6-11 years vs 2-5 years OR, 0.45, 95% CI, 0.42-0.49; age 12-17 years vs 2-5 years OR, 0.28, 95% CI, 0.25-0.31). Resident presence at induction was associated with increased odds of ETT use (OR, 1.50, 95% CI, 1.38-1.62). CONCLUSIONS: The decision to use NMB medication as part of an anesthetic plan increased substantially after sugammadex became available, particularly in older children and cases staffed by residents. ETT use declined over the study period.
RESUMEN
Introduction: Sarcopenia, an age-related disease, has become a major public health concern, threatening muscle health and daily functioning in older adults around the world. Changes in the gut microbiota can affect skeletal muscle metabolism, but the exact association is unclear. The richness of gut microbiota refers to the number of different species in a sample, while diversity not only considers the number of species but also the evenness of their abundances. Alpha diversity is a comprehensive metric that measures both the number of different species (richness) and the evenness of their abundances, thereby providing a thorough understanding of the species composition and structure of a community. Methods: This meta-analysis explored the differences in intestinal microbiota diversity and richness between populations with sarcopenia and non-sarcopenia based on 16 s rRNA gene sequencing and identified new targets for the prevention and treatment of sarcopenia. PubMed, Embase, Web of Science, and Google Scholar databases were searched for cross-sectional studies on the differences in gut microbiota between sarcopenia and non-sarcopenia published from 1995 to September 2023 scale and funnel plot analysis assessed the risk of bias, and performed a meta-analysis with State v.15. 1. Results: A total of 17 randomized controlled studies were included, involving 4,307 participants aged 43 to 87 years. The alpha diversity of intestinal flora in the sarcopenia group was significantly reduced compared to the non-sarcopenia group: At the richness level, the proportion of Actinobacteria and Fusobacteria decreased, although there was no significant change in other phyla. At the genus level, the abundance of f-Ruminococcaceae; g-Faecalibacterium, g-Prevotella, Lachnoclostridium, and other genera decreased, whereas the abundance of g-Bacteroides, Parabacteroides, and Shigella increased. Discussion: This study showed that the richness of the gut microbiota decreased with age in patients with sarcopenia. Furthermore, the relative abundance of different microbiota changed related to age, comorbidity, participation in protein metabolism, and other factors. This study provides new ideas for targeting the gut microbiota for the prevention and treatment of sarcopenia. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=475887, CRD475887.
RESUMEN
Carbon dioxide (CO2) has been widely used to enhance the recovery of adsorbed hydrocarbons from the organic matter (OM) in shale formations. To reveal the driving force of replacing adsorbed hydrocarbons from OM by CO2, we performed molecular dynamics (MD) simulations of the replacement process and calculated the interaction forces between CO2 and hydrocarbons. In addition, based on the umbrella sampling method, steered MD simulations were performed, and the free energy profiles of hydrocarbons were obtained using the weighted histogram analysis method. Results show that the condition of the hydrocarbon replacement by CO2 requires the hydrocarbon to have sufficient kinetic energy or to have a sufficiently large attractive force exerted to ensure that the hydrocarbon escapes the potential well of the OM. The attractive forces exerted on hydrocarbon molecules by CO2 can significantly decrease the energy barrier associated with hydrocarbon movement away from the OM surface. Furthermore, both CO2 and supercritical CO2 can effectively displace adsorbed hydrocarbon gas (methane) on the OM, while supercritical CO2 is required to enhance the recovery of adsorbed hydrocarbon oil (n-dodecane). The results obtained in this study provide guidance for enhancing the recovery of adsorbed hydrocarbons by CO2 in shale formations.
RESUMEN
The aroma profile of fermented chili pepper was analyzed using gas chromatography-mass spectrometry (GC-MS) coupled with chromatography-olfactometry (GC-O). A total of 19 aroma-active compounds were detected, exhibiting aroma intensities spanning from 1.8 to 4.2. And 12 aroma-active compounds were determined as pivotal odorants through odor activity value (OAV) calculation. Concentrations of these aroma-active compounds were quantified and subsequently employed in reconstructing the aroma profile of fermented chili pepper. Quantitative descriptive sensory analysis and electronic nose analysis proved that the aroma profile of fermented chili pepper was basically reconstituted. Omission experiments confirmed that methyl salicylate, linalool, 2-methoxy-3-isobutylpyrazine, and phenylethyl alcohol were the key aroma-active compounds of fermented chili pepper. Moreover, the perceptual interactions between the key aroma-active compounds were investigated. It was found that methyl salicylate masked the floral aroma, while phenylethyl alcohol had an additive effect on the aroma of linalool and 2-methoxy-3-isobutylpyrazine.
RESUMEN
Hemoproteins have recently emerged as powerful biocatalysts for new-to-nature carbene transfer reactions. Despite this progress, these strategies have remained largely limited to diazo-based carbene precursor reagents. Here, we report the development of a biocatalytic strategy for the stereoselective construction of pyridine-functionalized cyclopropanes via the hemoprotein-mediated activation of pyridotriazoles (PyTz) as stable and readily accessible carbene sources. This method enables the asymmetric cyclopropanation of a variety of olefins, including electron-rich and electrodeficient ones, with high activity, high stereoselectivity, and enantiodivergent selectivity, providing access to mono- and diarylcyclopropanes that incorporate a pyridine moiety and thus two structural motifs of high value in medicinal chemistry. Mechanistic studies reveal a multifaceted role of 7-halogen substitution in the pyridotriazole reagent toward favoring multiple catalytic steps in the transformation. This work provides the first example of asymmetric olefin cyclopropanation with pyridotriazoles, paving the way to the exploitation of these attractive and versatile reagents for enzyme-catalyzed carbene-mediated reactions.
Asunto(s)
Ciclopropanos , Triazoles , Ciclopropanos/química , Ciclopropanos/síntesis química , Triazoles/química , Triazoles/síntesis química , Estereoisomerismo , Piridinas/química , Piridinas/síntesis química , Estructura Molecular , BiocatálisisRESUMEN
Nine new oligophenalenone dimers, adpressins A-G (1-9), together with nine known compounds (10-18), were isolated from the fungus Talaromyces adpressus. Their chemical structures were determined on the basis of spectroscopic and mass spectral analyses. Their relative and absolute configurations were identified by 1H and 13C NMR calculations followed by DP4+ analyses, electronic circular dichroism (ECD) calculations, and ECD spectra comparison with related compounds. Compound 1 is the first example of a duclauxin derivative featuring an unusual 6/6/6/5/6/6/6 ring system, while compounds 6 and 7 contained a novel pyrrolidine ring. Compounds 5, 9, and 18 exhibited moderate inhibition against LPS-induced B lymphocyte proliferation with IC50 values ranging from 1.6 to 8.6 µM. Additionally, compounds 9 and 18 exhibited moderate inhibition against Con A-induced T lymphocyte proliferation with IC50 values of 9.3 and 2.6 µM, respectively.
Asunto(s)
Talaromyces , Talaromyces/química , Estructura Molecular , Fenalenos/farmacología , Fenalenos/química , Fenalenos/aislamiento & purificación , Animales , Ratones , Linfocitos T/efectos de los fármacos , Linfocitos B/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27-33 amino acids) were extracted and replicated 16 times for recombinant expression in Escherichia coli. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.
RESUMEN
Butylparaben, a common preservative, is widely used in food, pharmaceuticals and personal care products. Epidemiological studies have revealed the close relationship between butylparaben and diabetes; however the mechanisms of action remain unclear. In this study, we administered butylparaben orally to mice and observed that exposure to butylparaben induced glucose intolerance and hyperlipidemia. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with lipid metabolism, bile acid metabolism, and inflammatory response. Western blot results further validated that butylparaben promoted hepatic lipogenesis, inflammation, gluconeogenesis, and insulin resistance through the inhibition of the farnesoid X receptor (FXR) pathway. The FXR agonists alleviated the butylparaben-induced metabolic disorders. Moreover, 16 S rRNA sequencing showed that butylparaben reduced the abundance of Bacteroidetes, S24-7, Lactobacillus, and Streptococcus, and elevated the Firmicutes/Bacteroidetes ratio. The gut microbiota dysbiosis caused by butylparaben led to decreased bile acids (BAs) production and increased inflammatory response, which further induced hepatic glycolipid metabolic disorders. Our results also demonstrated that probiotics attenuated butylparaben-induced disturbances of the gut microbiota and hepatic metabolism. Taken collectively, the findings reveal that butylparaben induced gut microbiota dysbiosis and decreased BAs production, which further inhibited FXR signaling, ultimately contributing to glycolipid metabolic disorders in the liver.