Excessive climate warming exacerbates nitrogen limitation on microbial metabolism in an alpine meadow of the Tibetan Plateau: Evidence from soil ecoenzymatic stoichiometry.

Soil ecoenzymatic stoichiometry reflects the dynamic equilibrium between microorganism's nutrient requirements and resource availability. However, uncertainties persist regarding the key determinants of nutrient restriction in relation to microbial metabolism under varying degrees of warming. Our long-term and multi-level warming field experiment (control treatment, +0.42 °C, +1.50 °C, +2.55 °C) in a typical alpine meadow unveiled a decline in carbon (C)- and nitrogen (N)-acquired enzymes with escalating warming magnitudes, while phosphorus (P)-acquired enzymes displayed an opposite trend. Employing enzymatic stoichiometry modeling, we assessed the nutrient limitations of microbial metabolic activity and found that C and N co-limited microbial metabolic activities in the alpine meadow. Remarkably, high-level warming (+2.55 °C) exacerbated microbe N limitation, but alleviate C limitations. The structural equation modeling further indicated that alterations in soil extracellular enzyme characteristics (SES) were more effectively elucidated by microbial characteristics (microbial biomass C, N, P, and their ratios) rather than by soil nutrients (total nutrient contents and their ratios). However, the microbial control over SES diminished with higher levels of warming magnitude. Overall, our results provided novel evidence that the factors driving microbe metabolic limitation may vary with the degree of warming in Tibet alpine grasslands. Changes in nutrient demand for microorganism's metabolism in response to warming should be considered to improve nutrient management in adapting to different future warming scenarios.

Hollow UiO-66-NH2 encapsulated Pd catalysts for highly selective hydrogenation of furfural to furfuryl alcohol.

The selective hydrogenation of furfural (FFA) to furfuryl alcohol (FA) is regarded as attractive transformation to achieve the sustainable synthesis of value-added chemicals from biomass resources. However, the conventional supported catalysts are significantly restricted by their narrow pore size, ununiform dispersion and easy leaching or aggregation of catalytic sites. Herein, we designed hollow UiO-66-NH2 as the support to encapsulate Pd nanoparticles (Pd@H-UiO-66-NH2) to achieve the highly active and selective conversion of FFA to FA. Benefiting from the void-confinement effect and substrate enrichment of hollow structure, as well as the surface wrinkles, the as-prepared catalyst Pd@H-UiO-66-NH2 exhibited 96.8 % conversion of FFA with satisfactory selectivity reaching up to 92.4 % at 80 °C, 0.5 MPa H2 in isopropanol solvent within 6 h. More importantly, as-prepared Pd@H-UiO-66-NH2 catalyst exhibited excellent long-term stability, as well as good universality toward a series of hydrogenation of unsaturated hydrocarbons.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Human cytomegalovirus extensively re-organizes the human genome, diminishing TEAD1 transcription factor activity.

Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity. We confirm extensive concordant loss of TEAD1 binding, active H3K27ac histone marks, and chromatin looping interactions upon infection. Our data position TEAD1 at the top of a hierarchy involving multiple altered important developmental pathways. HCMV infection reduces TEAD1 activity through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of YAP1 and phosphorylated YAP1 levels, reduction of TEAD1 transcript and protein levels, and alteration of TEAD1 exon-6 usage. Altered TEAD1-based mechanisms are highly enriched at genetic risk loci associated with eye and ear development, providing mechanistic insight into HCMV's established roles in these processes.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

BF3 complexing phosphate/phosphonate ionic liquids: synthesis, characterization and thermophysical properties.

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X = dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] could be considered as metallic glass-forming liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 ℃) without melting, considerably low viscosities (33.876~58.117 mPa·s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography: A case report.

BACKGROUND: Multilocular thymic cyst (MTC) is a rare mediastinal lesion which is considered to occur in the process of acquired inflammation. It is usually characterized by well-defined cystic density and is filled with transparent liquid. CASE SUMMARY: We report on a 39-year-old male with a cystic-solid mass in the anterior mediastinum. Computer tomography (CT) imaging showed that the mass was irregular with unclear boundaries. After injection of contrast agent, there was a slight enhancement of stripes and nodules. According to CT findings, it was diagnosed as thymic cancer. CONCLUSION: After surgery, MTC accompanied by bleeding and infection was confirmed by pathological examination. The main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT findings. Caution is necessary in clinical work to avoid misdiagnosis.

Motif-Aware miRNA-Disease Association Prediction Via Hierarchical Attention Network.

As post-transcriptional regulators of gene expression, micro-ribonucleic acids (miRNAs) are regarded as potential biomarkers for a variety of diseases. Hence, the prediction of miRNA-disease associations (MDAs) is of great significance for an in-depth understanding of disease pathogenesis and progression. Existing prediction models are mainly concentrated on incorporating different sources of biological information to perform the MDA prediction task while failing to consider the fully potential utility of MDA network information at the motif-level. To overcome this problem, we propose a novel motif-aware MDA prediction model, namely MotifMDA, by fusing a variety of high- and low-order structural information. In particular, we first design several motifs of interest considering their ability to characterize how miRNAs are associated with diseases through different network structural patterns. Then, MotifMDA adopts a two-layer hierarchical attention to identify novel MDAs. Specifically, the first attention layer learns high-order motif preferences based on their occurrences in the given MDA network, while the second one learns the final embeddings of miRNAs and diseases through coupling high- and low-order preferences. Experimental results on two benchmark datasets have demonstrated the superior performance of MotifMDA over several state-of-the-art prediction models. This strongly indicates that accurate MDA prediction can be achieved by relying solely on MDA network information. Furthermore, our case studies indicate that the incorporation of motif-level structure information allows MotifMDA to discover novel MDAs from different perspectives. The data and codes are available at https://github.com/stevejobws/MotifMDA.

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis. / 艾灸对ApoE-/-åŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å°é¼ SIRT1/FOXO3a信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α-Helical Polypeptides to Optimize Antibacterial Therapy.

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.

Spindle component 25 predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis.

Spindle component 25 (SPC25) is one of the four proteins that make up the nuclear division cycle 80 (NDC80) complex, the other three components being Ndc80p, Nuf2p, and spindle component 24. Deregulation of the components of this complex can lead to uncontrolled proliferation and reduced apoptosis. However, the prognostic and immunotherapeutic value of SPC25 in pan-cancer remains unclear. Data from the UCSC Xena, TIMER2.0, and TCGA were analyzed to investigate the overall differential expression of SPC25 across multiple cancer types. The survival prognosis, clinical features, and genetic changes of SPC25 were also evaluated. Finally, the relationship between SPC25 and immunotherapy response was further explored through Gene Set Enrichment Analysis, tumor microenvironment, and immune cell infiltration. The transcription and protein expression of SPC25 were significantly increased in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, CESC, KIRC, KIRP, LIHC, LUAD, MESO, STAD, THYM, and UCEC. In some cancer types, SPC25 expression was also markedly correlated with the TMB, MSI, and clinical characteristics. Gene Set Enrichment Analysis showed that SPC25 was significantly associated with immune-related pathways. In addition, it was also confirmed that the expression level of SPC25 was strongly correlated with immune cell infiltration, immune checkpoint genes, immune regulatory genes, Ferroptosis-related genes, Cuproptosis-related genes, and lactate metabolism-related genes. This study comprehensively explored the potential value of SPC25 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy.

Exploring COVID-19 Phobia among International Chinese College Students in South Korea Before Ending COVID-19 Restrictions.

BACKGROUND: College students, considered to be the driving force of society, are highly vulnerable to COVID-19. At a time when facing a new pandemic wave in 2022, China's policy was in contrast with that of Korea. We investigated the phobia levels of international Chinese college students studying in Korea. OBJECTIVE: This study aimed to investigate the relationship between the frequency of use and trust of information sources, and COVID-19 phobia (C19P) among Chinese college students studying in Korea before ending related restrictions. METHODS: This study employed a cross-sectional design, conducting an online survey among Chinese college students studying in Korea from April 8-15, 2022 (before Korea ended the limitations due to COVID-19). Data about 319 respondents were analyzed, including socio-demographics, information variables, knowledge, attitudes, practices (KAP), and C19P. Hierarchical regression analysis with different models was used to examine the relationship between information trust, KAP, and C19P. RESULTS: Results showed that students performed well in knowledge and preventive practices, had diverse sources of getting information related to COVID-19, and highly depended on the internet and news. Students who perceived a higher severity of infection showed higher levels of COVID-19 phobia. The tendency to wear masks with family/friends, avoid crowded places, and not agree with Korean government mitigation policies reported higher levels of COVID-19 phobia. CONCLUSIONS: More authority and proactive communication strategies, such as consultations or education programs, are needed for international students to alleviate their phobias and psychological stress.

High biodegradability of microbially-derived dissolved organic matter facilitates arsenic enrichment in groundwater: Evidence from molecular compositions and structures.

Although biodegradation of organic matter is well-known to trigger enrichment of arsenic (As) in groundwater, the effects of DOM sources and biodegradability on As enrichment remain elusive. In this study, groundwater samples were collected from the Hetao basin to identify DOM source and evaluate biodegradability by using spectral and molecular techniques. Results showed that in the alluvial fan, DOM was mainly sourced from terrestrially derived OM, while DOM in the flat plain was more originated from microbially derived OM. Compared to terrestrially derived DOMs, microbially derived DOMs in groundwater, which had relatively higher H/Cwa ratios, NOSC values and more biodegradable molecules, exhibited higher biodegradability. In the flat plain, microbially derived DOMs with higher biodegradability encountered stronger biodegradation, facilitating the reductive dissolution of Fe(III)/Mn oxides and As enrichment in groundwater. Moreover, the enrichment of As depended on the biodegradable molecules that was preferentially utilized for primary biodegradation. Our study highlights that the enrichment of dissolved As in the aquifers was closely associated with microbially derived DOM with high biodegradability and high ability for primary biodegradation.

Ultra-Large Stress and Strain Polymer Nanocomposite Actuators Incorporating a Mutually-Interpenetrated, Collective-Deformation Carbon Nanotube Network.

Stimulus-responsive polymer-based actuators are extensively studied, with the challenging goal of achieving comprehensive performance metrics that include large output stress and strain, fast response, and versatile actuation modes. The design and fabrication of nanocomposites offer a promising route to integrate the advantages of both polymers and nanoscale fillers, thus ensuring superior performance. Here, it is started from a three-dimensional (3D) porous sponge to fabricate a mutually interpenetrated nanocomposite, in which the embedded carbon nanotube (CNT) network undergoes collective deformation with the shape memory polymer (SMP) matrix during large-degree stretching and releasing, increases junction density with polymer chains and enhances molecular orientation. These features result in substantial improvement of the overall mechanical properties and during thermally actuated contraction, the bulk SMP/CNT composites exhibit output stresses up to 19.5 ± 0.97 MPa and strains up to 69%, accompanied by a rapid response and high energy density, exceeding the majority of recent reports. Furthermore, electrical actuation is also demonstrated via uniform Joule heating across the self-percolated CNT network. Applications such as low-temperature thermal actuated vascular stent and wound dressing are explored. These findings lay out a universal blueprint for developing robust and highly deformable SMP/CNT nanocomposite actuators with broad potential applications.

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Vinpocetine represses the progression of nonalcoholic steatohepatitis in mice by mediating inflammasome components via NF-KB signaling / La vinpocetina reprime la progresión de la esteatohepatitis no alcohólica en ratones por mediación de los componentes del inflamasoma a través de la señalización NF-KB

Background: Inflammasome activation is known to be involved in nonalcoholic steatohepatitis (NASH). Vinpocetine is a derivative of vincamine and is reported to suppress the activation of inflammasome. Methods: This study explored the therapeutical potential of Vinpocetine on NASH. Mice were fed with a choline-deficient (MCD) or chow diet in the presence or absence of Vinpocetine for 8 weeks. H&E staining and biochemical assays were determined to evaluate the hepatic steatosis and fibrosis symptoms. In addition, primary hepatocytes and Kupffer cells were isolated and induced by MCD or lipopolysaccharides/cholesterol crystals with or without Vinpocetine. ELISAs, qPCR, and Western blotting were applied to determine the levels of NASH-related biomarkers in both in vivo mouse model and in vitro cell models. Results: Treatment of Vinpocetine did not cause observable side effects against and MCD-induced cells and mouse NASH model. However, treatment of Vinpocetine ameliorated hepatic steatosis and fibrosis and suppressed the levels of alanine transaminase and aspartate transferase in the mouse NASH model. In addition, treatment of Vinpocetine suppressed the mRNA and protein levels of inflammasome components both in vitro and in vivo. Conclusion: Vinpocetine suppressed NASH in mice by mediating inflammasome components via nuclear factor κB signaling. (AU)

Antecedentes: Se sabe que la activación del inflamasoma está implicada en la esteatohepatitis no alcohólica (EHNA). La vinpocetina es un derivado de la vincamina que, según los informes, suprime la activación del inflamasoma. Métodos: Este estudio exploró el potencial terapéutico de la vinpocetina en la EHNA. Durante 8 semanas se alimentó a ratones con una dieta deficiente en colina (MCD) o con una dieta chow en presencia o ausencia de vinpocetina. Se realizaron tinciones de H&E y ensayos bioquímicos para evaluar los síntomas de esteatosis hepática y fibrosis. Además, se aislaron hepatocitos primarios y células de Kupffer y se indujeron mediante MCD o cristales de lipopolisacáridos/colesterol con o sin vinpocetina. Se aplicaron ELISA, qPCR y Western blotting para determinar los niveles de biomarcadores relacionados con la EHNA tanto en el modelo de ratón in vivo como en los modelos celulares in vitro. Resultados: El tratamiento con vinpocetina no causó efectos secundarios observables contra las células y el modelo de ratón de EHNA inducidos por MCD. Sin embargo, el tratamiento con vinpocetina mejoró la esteatosis hepática y la fibrosis y suprimió los niveles de alanina transaminasa y de aspartato transferasa en el modelo de EHNA de ratón. Además, el tratamiento con vinpocetina suprimió los niveles de ARNm y proteínas de los componentes del inflamasoma tanto in vitro como in vivo. Conclusiones: La vinpocetina suprimió la EHNA en ratones por mediación de los componentes del inflamasoma a través de la señalización del factor nuclear κB. (AU)

Study on the Effect of Polyamine Water Treatment Agent on Metal Corrosion Inhibition in Boiler Steam-Water System.

A polyamine water treatment agent was prepared with the film-forming amine (N-oleyl-1,3-propylenediamine) and the neutralizing amine (cyclohexanamine) under optimal conditions. The copper sulfate liquid drop experiment showed that a protective film was formed by the polyamine water treatment agent on carbon steel. The analyses of the polarization curve and electrochemical impedance spectroscopy of carbon steel indicated that the polyamine water treatment agent exhibited geometric effects, which could inhibit both anode and cathode reactions of carbon steel, and the corrosion inhibition effect of the polyamine water treatment agent showed an extreme-concentration phenomenon. A metal corrosion experiment in a simulated boiler steam-water system indicated that the polyamine water treatment agent mitigated the corrosion of carbon steel at different temperatures, and the corrosion inhibition rates of the polyamine water treatment agent in liquid and gas environments at 150 °C were 53.84% and 67.43%, respectively, better than that at 350 °C. SEM-EDS characterization indicated that the formation of the corrosion product, iron oxide, on the carbon steel was reduced with the addition of the polyamine water treatment agent in the simulated boiler steam-water system.