Search

Abstract Renal tubular epithelial cells (TECs) play a critical role in driving acute kidney injury (AKI) progression, but the key molecular features in TECs during this process is not clear. To better understand the molecular characteristics in renal TECs during AKI and renal fibrogenesis, an irreversible AKI mouse model induced by ischemia/reperfusion injury (IRI) was used in this study. The renal tubules were isolated and tubule specific transcriptome was detected by RNA-seq at different stages in the progression of AKI in this model. The overall transcriptome indicated injury and repair process of TEC after renal IRI. In addition, metabolism maladaption was observed during AKI progression to chronic fibrosis. Particularly, we found dysregulation of multiple steps of lipid metabolism in tubule transcriptomes. Oil red O staining revealed massive lipid droplets accumulation in TECs at day 10, thus confirming the defect of lipid metabolism. This is the first study to charaterize renal tubule specific transcriptome during AKI progression. The results shed light on the molecular features in TECs for progressive AKI. Highlights • We used the most common AKI model caused by renal ischemia/reperfusion injury (IRI) and established a severe AKI model with progressive renal pathology. • This study is the first to isolate renal tubules and charaterize tubular specific transcriptome during AKI progression. • Tubule specific transcriptome revealed that the deregulation of lipid metabolism occurred in multi-step wise, particularly in the process of lipid transport and FAO inhibition, which may result in TECs apoptosis, dedifferentiation and renal fibrogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Micrococcal nuclease (MNase) is extensively used in genome-wide mapping of nucleosomes but its preference for AT-rich DNA leads to errors in establishing precise positions of nucleosomes. Here, we show that the MNase digestion of nucleosomes assembled on a strong nucleosome positioning sequence, Widom's clone 601, releases nucleosome cores whose sizes are strongly affected by the linker DNA sequence. Our experiments produced nucleosomal DNA sizes varying between 147 and 155bp, with positions of the MNase cuts reflecting positions of the A⋅T pairs rather than the nucleosome core/linker junctions determined by X-ray crystallography. Extent of chromatosomal DNA protection by linker histone H1 also depends on the linker DNA sequence. Remarkably, we found that a combined treatment with MNase and exonuclease III (exoIII) overcomes MNase sequence preference producing nucleosomal DNA trimmed symmetrically and precisely at the core/linker junctions regardless of the underlying DNA sequence. We propose that combined MNase/exoIII digestion can be applied to in situ chromatin for unbiased genome-wide mapping of nucleosome positions that is not influenced by DNA sequences at the core/linker junctions. The same approach can be also used for the precise mapping of the extent of linker DNA protection by H1 and other protein factors associated with nucleosome linkers. [Copyright &y& Elsevier]

Abstract: Heterogeneous chiral catalysts were prepared by modifying silica-supported rhodium (Rh/SiO2) with chiral phosphorus ligands. The chirally modified Rh/SiO2 catalysts exhibited high activity, regioselectivity, and enantioselectivity for the asymmetric hydroformylation of styrene and vinyl acetate. Up to 72% ee and 100% selectivity of branched aldehyde for the hydroformylation of vinyl acetate were obtained for (R)-BINAP–Rh/SiO2 catalysts. It is noteworthy that the modification of Rh/SiO2 with (S,S)-DIOP resulted in increased activity for the hydroformylation of vinyl acetate and gave a TOF of 128 h−1, even higher than that of the unmodified Rh/SiO2 catalyst (90 h−1). It is found that chiral modifiers with bidentate phosphines and an optimized modifier/rhodium molar ratio close to 1.0 were prerequisites for chiral induction on the chirally modified catalysts. MAS NMR results and IR spectra of adsorbed CO indicated that the chiral modification via the coordination of phosphines to rhodium produces chirally active sites on the Rh/SiO2 catalysts. [Copyright &y& Elsevier]

• Transmissibility function is used to detect debonding beneath concrete pavement. • Transmissibility damage indicators are proposed to represent debonding. • Theoretical deduction and FEA are conducted to study debonding effects. • TFs at higher frequency range are more sensitive to the debonding. • Field test results demonstrate the feasibility of the TF-based method. This paper proposes a novel method to detect and localize debonding beneath the concrete pavement using transmissibility function (TF) analysis. The layout of the measurement node array, the signal processing approach, and the testing procedures are proposed. Two matrices of transmissibility damage indicator (TDI) are proposed to describe the distribution of debonding. This method is a response-only approach and can offer advantages in easy and low-cost implementation. The theoretical deduction, finite element analysis (FEA), and field tests are conducted to demonstrate and verify detection and localization performance. It is first observed that the arrangement of measurement nodes and the frequency range are crucial to TF analysis. TFs at higher frequencies range are more sensitive to the debonding but may result in higher errors. The density of the measurement node array and the noise's effect are investigated in the FEA. Using a denser node array and maintaining a lower noise level helps localize the debonding more precisely. Field tests are conducted on a precast concrete pavement plate using a specially designed accelerometer array. The test results demonstrate the feasibility of the TF-based method for debonding detection and localization. [ABSTRACT FROM AUTHOR]

It is an urgent challenge to coordinate industrialization and air quality in China since the rapid industrialization over the past forty years caused serious air pollution. In this paper, we measured the industrialization levels of the 31 regions in China from 2003 to 2017 as a sum of per capita gross domestic product (GDP), urban population (% of total), tertiary vs. secondary industry output ratio, non-agricultural output value (% of GDP), non-agricultural employment proportion, and the proportion of added value of manufacturing in the total added value of commodity. We measured air quality as a sum of annual SO 2 , NO 2 and PM 10 concentrations. In general, the industrialization level continuously increased while air pollution was reduced in spite of some fluctuations in China. Our results show air pollution presented N-shape relations with the industrialization level in China in the periods from 2003 to 2008, 2009 to 2013, and 2014 to 2017. Air pollution increases as the industrialization occurs but later deceases as the industrialization level improves. However, air pollution rebounds as the industrialization moves further but this rebound became weaker in recent years. With the association rule mining, we identified ranges of the six indicators for industrialization associated with good and poor air quality, respectively. Using industrialization indicators associated with poor air quality as references, we pointed out differentiated strategies for regions to coordinate the industrialization and air quality protection. • We analyzed industrialization progress & air quality from 2003 to 2017 in China. • Air pollution in China exhibits N-shape relations with industrialization level. • We mined association rules between industrialization indicators and air quality. • Summary of industrialization indicator ranges associated with good/poor air quality. • Differential strategy by region to coordinate development & air quality protection. [ABSTRACT FROM AUTHOR]

The mammalian Na + /H + exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr 653 was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr 653 is an important regulatory amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity. [ABSTRACT FROM AUTHOR]

Abstract: The combination of magnetic nanoparticles and mesoporous silica can present a strategy for enzyme immobilization. In this work, magnetic siliceous mesocellular foam functionalized with octyl groups was prepared and used as support for lipase adsorption. Almost all the active lipases in crude enzyme solution were adsorbed by this magnetically separable, hydrophobic siliceous mesocellular foam. The resolution of 1-phenylethanol acylated with vinyl acetate can be achieved in 1.5h using the resultant magnetic biocatalyst, whereas only 30% conversion was obtained by using the free lipase under the identical reaction conditions. These results are probably due to the “interfacial adsorption” and “hyper-activation” of lipase on the hydrophobic surface of the magnetic siliceous mesocellular foam. Moreover, the biocatalyst entrapped in the nanopores of this foam can be recycled magnetically for at least seven times without significant loss of its activity and enantioselectivity. [Copyright &y& Elsevier]

Nuclear receptor subfamily 4 group A member 1 (NR4A1) acts as a myogenic factor in muscle development and regeneration; however, it remains unclear how Nr4a1 regulates myoblast physiology. In this study, report a role for Nr4a1-mediated regulation of cell adhesion in myoblast and muscle tissue. Nr4a1 -overexpression myoblast, Nr4a1 -konckdown myoblast and mice gastrocnemius muscle following an injection with an adenovirus vector expression Nr4a1 (Nr4a1-AAV) were used to observe the changes in cell adhesion. Nr4a1 was found to enhance cell-cell contact and adhesion molecule expression in myoblasts. In contrast, the deletion of Nr4a1 expression inhibited junction and adhesion between myoblasts. Moreover, Nr4a1 increased myoblast adhesion via directly binding to an upstream site of zinc finger E-box binding homeobox 1 (Zeb1), which is required for myogenesis in myoblasts. In mice, Zeb1 induced increased cadherin and integrin expression in the gastrocnemius muscle following an injection with an adenovirus vector expressing Nr4a1(Nr4a1-AAV). These data indicate that Nr4a1 regulates myoblast adhesion via Zeb1 expression. • Nr4a1 overexpression enhances myoblast contact and cell adhesion molecule levels. • Nr4a1 silencing decreases myoblast contact and cell adhesion molecule expression. • The effect of Nr4a1 on myoblast adhesion and fusion involves Zeb1. [ABSTRACT FROM AUTHOR]

• People with epilepsy strongly desire to access information related to epilepsy, but lack reliable and easily accessible sources. • ChatGPT provide accurate and consistent answers to common concerns in patients withepilepsy, helping them better understand their condition. • ChatGPT may generate incorrect answers, leading users to adopt incorrect and potentially harmful advice. • ChatGPT is suitable for patient education and should be used as an information channel rather than a basis for decision-making at this stage. • ChatGPT can offer emotional support that may benefit for patients experiencing specific emotional distress. People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education. [ABSTRACT FROM AUTHOR]

• According to the American Academy of Neurology guidelines, for children seizure-free for 18–24 months post-epilepsy surgery, a discussion on the risks and benefits of ASM withdrawal is recommended. • We attempted early withdrawal of antiseizure medications in 99 children who were seizure free after resection surgery and the most obvious finding to emerge from this study is that early ASM withdrawal is relatively viable and safe. • Approximately one in five children experienced seizure recurrence during or after ASM withdrawal and 60% of patients with recurrent seizure immediately returned to seizure free after restart and optimized ASM. • Incomplete resection and postoperative seizures prior to ASM withdrawal are independent predictors of seizure recurrence. The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period. [ABSTRACT FROM AUTHOR]

The lectins are a large family of carbohydrate-binding proteins that play important roles in the innate immune response of various organisms. Although C-type lectin domain family 3 member B (CLEC3B), an important member of C-type lectin, has been well documented in humans and several other higher vertebrates, little is currently known about this molecule in economically important marine fish species. In this study, through transcriptomic and BLAST screening, a novel CLEC3B gene was identified in the golden pompano (Trachinotus ovatus). The T. ovatus CLEC3B (ToCLEC3B) was subsequently characterized by bioinformatic analysis and compared with those reported in other species. In addition, the expression patterns of ToCLEC3B in different tissues under normal condition and at different times post pathogen challenge were assessed. Furthermore, the agglutinating activity of To CLEC3B with and without Ca2+ against different bacteria and blood cells of donor species were verified using the recombinant T. ovatus CLEC3B (r To CLEC3B). Our results demonstrated that To CLEC3B is a Ca2+-dependent galactose-binding lectin with a single copy of carbohydrate recognition domain (CRD). Similar to CLEC3B reported in other species, the CRD domain of To CLEC3B consists of two α-helices, six β-sheets, and four loops, forming two Ca2+- and a galactose-binding sites. According to the phylogenetic analysis, the ToCLEC3B was highly similar (similarity at 95.00%) to that of its relative, the greater amberjack (Seriola dumerili). The expression of ToCLEC3B was detected in all tissues examined under normal condition and was significantly up-regulated by injection of pathogenic microbes. In addition, the r To CLEC3B exhibited strong agglutinating activity against different bacteria and blood cells of donor species in the presence of Ca2+. Our results indicate that To CLEC3B is a constitutive and inducible acute-phase immune factor in the host's innate immune response of T. ovatus. • A novel CLEC3B gene (ToCLEC3B) was identified in the marine fish T. ovatus. • To CLEC3B had a carbohydrate recognition domain with Ca2+ and galactose-binding sites. • ToCLEC3B expression was shown to be significantly up-regulated by pathogen challenge. • Recombinant To CLEC3B showed strong agglutinating activity against alien substances. • Results indicate To CLEC3B is a constitutive and inducible acute-phase immune factor. [ABSTRACT FROM AUTHOR]

Policies directly or indirectly influence the development of industrial symbiosis (IS). Quantitatively analyzing the effects of policies on IS at a national level is necessary, but current research has lagged. Focusing on the symbiotic system that includes the thermal power industry, cement industry, iron and steel industry, and social sector in China, this paper assesses the efficacy of policies on this nationwide IS system between 2015 and 2022. A policy influence framework is proposed, combining a cost-benefit analysis, agent-based model, and comparative analysis. Results show: (1) the symbiosis probability of the nationwide IS system experiences a fluctuating increase. The maximum increments of the symbiosis probability are 5%, and the resulting environmental benefits are equivalent to an emission reduction of 6.99 Mt from blast furnace slag, 20.97 Mt from iron mine tailing, 36.02 Mt from household waste, 25.01 Mt from steel slag, and 22.95 Mt from fly ash. However, the stimulation effects of policies vary across different subsystems. (2) Thermal power-chemical subsystems, thermal power-environmental protection subsystems, iron and steel-environmental protection subsystems, and social sector-cement subsystems need policy support in the future. (3) Approximately 50% of fields in this nationwide IS system is insensitive to current policies; policy approaches should shift from economic stimulation to symbiotic guidance. This paper fills the research gap by quantitatively studying the IS policy efficacy from a national level. The findings can contribute to the improvement of the Chinese IS policy system. [Display omitted] • Quantitatively analyzing the effects of policy on industrial symbiosis at a national level. • Policy-sponsored incentive effects vary across different types of waste and subsystems. • Half of the symbiotic utilization fields are insensitive to current policy. • The policy should shift from economic stimulation to symbiotic utilization guidance. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca 2+ /calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca 2+ /CaMKII signaling pathways. [ABSTRACT FROM AUTHOR]

Transcription factor FOXM1 plays a critical role in maintenance of stem cell pluripotency through stimulating the transcription of pluripotency-related genes in mouse pluripotent stem cells. In this study, we have found that the repression of FOXM1 expression is mediated by FOXM1 3′UTR during retinoic acid-induced differentiation of human pluripotent NT2/D1 embryonal carcinoma cells. FOXM1 3′UTR contains a microRNA response element (MRE) for miR-134, which has been shown to attenuate the expression of pluripotency-related genes post-transcriptionally during mouse embryonic stem cell differentiation. We have determined that miR-134 is induced during RA-induced differentiation of NT2/D1 cells and the overexpression of miR-134 represses the expression of FOXM1 protein but not FOXM1 mRNA. Furthermore, the expression of OCT4 is diminished by FOXM1 knockdown and the OCT4 promoter is regulated directly by FOXM1, suggesting that FOXM1 is required for maintaining the expression of OCT4 in NT2/D1 cells. Together, our results suggest that FOXM1 is essential for human pluripotent stem cells and miR-134 attenuates its expression during differentiation. [ABSTRACT FROM AUTHOR]

Abstract: ATP-sensitive K+ (KATP) channels couple intermediary metabolism to cellular activity. Genetic disruption of these channels impairs glucose homeostasis. Similar effects occur from a single-nucleotide polymorphism of the Kir6.2 subunit seen in greater than 50% of the human population, which causes a point mutation of Glu23 to lysine. This E23K variant shows higher susceptibility to diabetes due to mechanisms that are not fully understood. This study was designed to examine the dysregulation of E23K on insulin sensitivity in the presence of long-chain fatty acyl CoA (LC-CoA), a major active form of free fatty acids. Physiological concentrations of LC-CoA decreased insulin sensitivity in E23K-transfected L6 muscle cells by increasing the activation of negative regulators in the insulin signaling pathway. LC-CoA also reduced IRS-1 and Akt phosphorylation and glucose transport. This effect was not due to the expression of the E23K mutant on cell membrane. Our results indicate that E23K could impair insulin sensitivity, thus predisposing E23K carriers to insulin resistance. [Copyright &y& Elsevier]