Strong associations between fasting lipids and glucose concentrations and ALT levels strengthened with increasing ALT quantiles.

BACKGROUND: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. METHODS: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. RESULTS: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. CONCLUSIONS: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

Synthesis and evaluation of homocamptothecin antibody-drug conjugates for cancer treatment.

As an emerging tumor therapeutic strategy, antibody-drug conjugates (ADCs) overcome the high toxicity of traditional small molecule chemotherapy and improve the targeting of treatment. In this study, we successfully constructed a novel ADC, Tras-16b, for the first time using homocamptothecin 16b as the payload. Tras-16b, at a dose of 3 mg/kg, exhibited comparable anti-tumor activity to Enhertu and demonstrated an enhanced safety profile in the NCI-N87 xenograft model. Notably, this is the first ADC developed based on homocamptothecin, marking a significant advancement with promising prospects for the structural modification of camptothecin ADCs.

Umbilical cord mesenchymal stem cells in ulcerative colitis treatment: efficacy and possible mechanisms.

BACKGROUND: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. METHODS: This prospective, self-controlled clinical study was conducted at Henan Provincial People's Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. RESULTS: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1ß, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. CONCLUSION: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. TRIAL REGISTRATION: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Source apportionment of organic carbon and nitrogen in sediments from river and lake in the highly urbanized Changjiang Delta.

While the impact of human activities on organic matter pollution is recognized, how these impacts vary seasonally in the Changjiang Delta needs further investigation. This study addresses this gap by investigating seasonal variations in organic matter sources and ecological responses to human activities in Changjiang Delta sediments. Total organic carbon (TOC), total nitrogen (TN), and carbon (δ13C) and nitrogen (δ15N) isotopic compositions of surface sediments collected from the Taipu River and Dalian Lake wetland were analyzed. Both water bodies exhibited similar seasonal trends for TOC and TN, with the Taipu River containing an average of 0.46% and 0.03% higher concentrations of TOC and TN, respectively, compared to Dalian Lake. Additionally, the organic index (OI) and organic nitrogen (ON) index were elevated in both water bodies during the wet season. Sediments from Dalian Lake remained uncontaminated to moderately contaminated, while those from the Taipu River were generally classified as moderately to heavily contaminated. Stable isotope analysis identified terrestrial C3 plants (averaging 25.5%), C4 plants (averaging 16.0%), and municipal wastewater (averaging 16.0%) as the main contributors to organic matter in the sediments. These findings suggest that terrestrial plant material and municipal wastewater are key targets for managing organic matter contamination in the Changjiang Delta. Implementing strategic land-use planning and targeted interventions to minimize these inputs can significantly improve water quality and ecosystem health.

The Different Influence of Cutibacterium Acnes and Staphylococcus Epidermidis in the Lumbar Disc: An in Vivo Study in Rabbits.

STUDY DESIGN: Animal laboratory study. OBJECTIVE: This study investigated the effects of C. acnes and S. epidermidis on the lumbar discs of rabbits, as well as the outcomes of combined infection. SUMMARY OF BACKGROUND DATA: Many studies have indicated that bacterial infections are associated with lumbar disc degeneration (LDD). The most commonly cultured bacteria from disc tissues are Cutibacterium acne (C. acnes) and Staphylococcus epidermidis (S. epidermidis). METHODS: New Zealand white rabbits (n=40) were randomly divided into control, C. acnes, S. epidermidis, and C. acnes plus S. epidermidis (i.e., combined) groups. All groups except the control were injected with 25 µL of saline at L4-L5 and 25 µL of bacteria (1×107 CFU/mL) at L5-L6. All injections were performed under X-ray guidance. Weight measurements, haematological evaluations, and magnetic resonance imaging were performed after 4, 8, and 12 weeks. Histological examination and gene expression detection were performed 12 weeks after surgery. RESULTS: Inflammatory factors in the blood and weight did not differ among the groups after 4, 8, and 12 weeks (P >0.05). However, after 4 weeks, LDD occurred in the C. acnes group, and discitis occurred in the S. epidermidis and combined groups, all of which worsened after 8 weeks. After 12 weeks, the nucleus pulposus (NP) protruded and compressed the spinal cord in the C. acnes group, and tissue staining showed decreased NP tissue and cartilaginous endplate fracture. In the S. epidermidis and combined groups, the discitis was more confined, but tissue staining revealed a significant decrease in NP tissue, and loss of the normal disc structure. CONCLUSIONS: In the early stage of infection in rabbits, C. acnes caused LDD, and S. epidermidis caused discitis. Co-infection with C. acnes and S. epidermidis caused discitis but was more limited in scope than infection with S. epidermidis alone.

Anchorage Research for CFRP Tendons: A Review.

Carbon fiber reinforced polymer (CFRP) tendons are composite materials that offer significant advantages in terms of tensile strength and lightweight properties. They are being increasingly utilized in the construction industry, particularly in bridge cables and building structures. However, due to their relatively poor transverse mechanical properties compared to steel cables, securing these tendons with anchors presents a challenge. This paper reviews the structure and force characteristics of three types of anchors for CFRP tendons-clamping anchorage, bonded anchorage, and composite anchorage-analyzes and summarizes the anchorage characteristics and damage mechanisms of each type of anchorage, and highlights that the optimization of the mechanical properties of the tendons is key to the design and research of anchoring systems. The new composite anchorage offers comprehensive advantages, such as minimal tendon damage at the anchorage section, more uniform stress distribution, and better anchorage performance, despite being more complex in design compared to single-type anchorages. However, there remain challenges and research gaps in testing and validating these anchoring systems under realistic loading and environmental conditions, including impacts, cyclic stresses, humidity, and high temperatures. Future efforts should focus on developing new testing techniques and models to simulate real-world conditions, enabling more accurate assessments of anchorage performance and longevity. By doing so, we can fully harness the mechanical properties of CFRP tendons and further enhance the safety and efficiency of our built environment.

Infrared photodetectors based on wide bandgap two-dimensional transition metal dichalcogenides via efficient two-photon absorption.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted considerable attention due to their outstanding optoelectronic properties and ease of integration, making them ideal candidates for high-performance photodetectors. However, the excessive width of the bandgap in some 2D TMDs presents a challenge for achieving infrared photodetection. One approach to broaden the photoresponse wavelength range of TMDs is through the utilization of two-photon absorption (TPA) process. Unfortunately, the inefficiency of TPA hinders its application in infrared photodetection. In this study, we propose the design of two photodetectors utilizing high TPA coefficient materials, specifically ReSe2and MoS2, to exploit their TPA capability and extend the photoresponse to the near-infrared region at 1550 nm. The ReSe2photodetector demonstrates an unprecedented responsivity of 43µA W-1, surpassing that of current single-material TPA photodetectors. Similarly, the MoS2photodetector achieves a responsivity of 18µA W-1, comparable to state-of-the-art TPA photodetectors. This research establishes the potential of high TPA coefficient 2D TMDs for infrared photodetection.

Dencichine/palygorskite nanocomposite incorporated chitosan/polyvinylpyrrolidone film for accelerating wound hemostasis.

The development of efficient, safe, environmentally friendly, and user-friendly hemostatic dressings remains a great challenge for researchers. A variety of clay minerals and plant extracts have garnered considerable attention due to their outstanding hemostatic efficacy and favorable biosafety. In this study, a facile solution casting strategy was employed to prepare nanocomposite films by incorporating natural nanorod-like palygorskite (Pal) and herb-derived hemostat dencichine (DC) based on chitosan and polyvinylpyrrolidone. The dynamic blood clotting index demonstrated that the nanocomposite film with a DC addition of 1.0 wt% exhibited significantly superior hemostatic properties compared to both pure DC powder or commercial hemostatic agent Yunnan Baiyao. This improvement was primarily attributed to proper blood affinity, increased porosity, enhanced adhesion of platelets and erythrocytes, as well as the accelerated activation of coagulation factors and platelets. Under the synergistic effect of Pal and DC, the nanocomposite film displayed suitable tensile strength (20.58 MPa) and elongation at break (47.29 %), which may be due to the strong intermolecular hydrogen bonding and electrostatic interaction between Pal/DC and macropolymers. Notably, the nanocomposite film exhibited remarkable antibacterial effectiveness and desirable cytocompatibility, as well as the capability of promoting wound healing in vitro. Taken together, the nanocomposite film synergized with Pal and DC is expected to be an efficacious and suitable wound dressing.

Enhancing Electrocatalytic Kinetics via Synergy of Co Nanoparticles and Co/Ni-N4-C- and N-Doped Porous Carbon.

Transition-metal species embedded in carbon have sparked intense interest in the fields of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, improvement of the electrocatalytic kinetics remains a challenge caused by the synergistic assembly. Here, we propose a biochemical strategy to fabricate the Co nanoparticles (NPs) and Co/Ni-N4-C co-embedded N-doped porous carbon (CoNPs&Co/Ni-N4-C@NC) catalysts via constructing the zeolitic imidazolate framework (ZIF)@yeast precursor. The rich amino groups provide the possibility for the anchorage of Co2+/Ni2+ ions as well as the construction of Co/Ni-ZIF@yeast through the yeast cell biomineralization effect. The functional design induces the formation of CoNPs and Co/Ni-N4-C sites in N-doped carbon as well as regulates the porosity for exposing such sites. Synergy of CoNPs, Co/Ni-N4-C, and porous N-doped carbon delivered excellent electrocatalytic kinetics (the ORR Tafel slope of 76.3 mV dec-1 and the OER Tafel slope of 80.4 mV dec-1) and a high voltage of 1.15 V at 10 mA cm-2 for the discharge process in zinc air batteries. It provides an effective strategy to fabricate high-performance catalysts.

The hemostatic performance and mechanism of palygorskite with structural regulate by oxalic acid gradient leaching.

Palygorskite (Pal) is a naturally available one-dimensional clay mineral, featuring rod-shaped morphology, nanoporous structure, permanent negative charges as well as abundant surface hydroxyl groups, exhibiting promising potential as a natural hemostatic material. In this study, the hemostatic performance and mechanisms of Pal were systematically investigated based on the structural regulate induced by oxalic acid (OA) gradient leaching from perspectives of structure, surface attributes and ion release.In vitroandin vivohemostasis evaluation showed that Pal with OA leaching for 1 h exhibited a superior blood procoagulant effect compared with the raw Pal as well as the others leached for prolonging time. This phenomenon might be ascribed to the synergistic effect of the intact nanorod-like morphology, the increase in the surface negative charge, the release of metal ions (Fe3+and Mg2+), and the improved blood affinity, which promoted the intrinsic coagulation pathway, the fibrinogenesis and the adhesion of blood cells, thereby accelerating the formation of robust blood clots. This work is expected to provide experimental and theoretical basis for the construction of hemostatic biomaterials based on clay minerals.

From gut to brain: understanding the role of microbiota in inflammatory bowel disease.

With the proposal of the "biological-psychological-social" model, clinical decision-makers and researchers have paid more attention to the bidirectional interactive effects between psychological factors and diseases. The brain-gut-microbiota axis, as an important pathway for communication between the brain and the gut, plays an important role in the occurrence and development of inflammatory bowel disease. This article reviews the mechanism by which psychological disorders mediate inflammatory bowel disease by affecting the brain-gut-microbiota axis. Research progress on inflammatory bowel disease causing "comorbidities of mind and body" through the microbiota-gut-brain axis is also described. In addition, to meet the needs of individualized treatment, this article describes some nontraditional and easily overlooked treatment strategies that have led to new ideas for "psychosomatic treatment".

Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study.

BACKGROUND: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. METHOD: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. RESULTS: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. CONCLUSION: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

The influence of climate and human factors on a regional heat island in the Zhengzhou metropolitan area, China.

The development of urbanization and the establishment of metropolitan areas causes the urban heat island to cross the original single-city scale and form a regional heat island (RHI) with a larger influence range. Due to the decreasing distance between cities, there is an urgent need to reevaluate RHI for urban agglomerations, considering all cities instead of a conventional single-city perspective. The impact of climatic conditions and human factors on heat islands still lacks a general method and framework for systematic evaluation. Therefore, we used land and night light data as background conditions to study the diurnal and seasonal changes of heat islands in the Zhengzhou metropolitan area, China. Pearson correlation analysis and random forest regression analysis were then used to explore the influence of climatic conditions and human factors on RHI and its internal relationship. We found that the daytime RHI had strong spatial heterogeneity and seasonal differences from 2001 to 2020. The daytime RHI was stronger than nighttime in spring, summer, and autumn, and the nighttime RHI was stronger than daytime in winter. From spring to winter, RHI increased first and then decreased during the daytime, while the opposite was observed at night. In this study, temperature has a greater effect on daytime RHI; CO2 and NL have a greater effect on nighttime RHI. There was strong spatial heterogeneity in the effects of climatic conditions and human factors on the RHI, with climatic conditions contributing more to the daytime RHI in the northern mountainous areas, while human factors had a greater impact on the nighttime RHI in the main urban areas of each location. The results of this study highlight more targeted and informed strategies for RHI mitigation in the Zhengzhou metropolitan area and provide helpful insights into RHI evaluation in other urban agglomerations.

Clarifying the correlations between hydraulic indicators evaluating the hydraulic performance of free water surface constructed wetlands.

Previous studies have shown a strong linear correlation between the common hydraulic indicators of free water surface constructed wetlands (FWS CWs), which results in the waste of computing resources and confusion in evaluating the hydraulic performance of FWS CWs. There is an urgent need to define a relatively independent and authoritative hydraulic indicator. In this study, based on three years' data, the correlations among five representative hydraulic indicators, that is, short-circuit index (φ10), Morrill dispersion index (MDI), effective volume ratio (e), moment index (MI), and hydraulic efficiency (λe), were analyzed by combining a variety of methods. The results of the correlation analysis and principal component analysis clearly showed the positive correlations among φ10, e, MI, and λe (p < 0.01), and the strong negative correlations between MDI and the remaining four indexes, which were further confirmed by redundancy analysis (RDA). Most importantly, the significant correlations between MI vs e and φ10 vs e were proved through rigorous mathematical reasoning for the first time. Besides, the results of RDA indicated that the studied design parameters, namely, water depth, hydraulic loading rate, plant spacing, aspect ratio, layout of inlet and outlet, and plant species, could generally explain the variation in hydraulic indicators. The layout of inlet and outlet displayed positive effects on hydraulic performance, and the water depth exhibited negative effects. Combining the clarity of physical meaning, convenience of calculation, and universality of reflecting both hydraulic and treatment performances, e was recommended as the most authoritative hydraulic indicator to evaluate hydraulic performance. The clustering results based on e were highly consistent with those based on the comprehensive principal component score. Wetlands with a combination of lower water depth and better layout of inlet and outlet usually have better hydraulic performance. This study successfully revealed the significant correlations among hydraulic indicators and their sources, and recommended a unique hydraulic indicator to authoritatively evaluate the hydraulic performance of FWS CWs.

Organic photoredox-catalyzed oxidative azolation of unactivated fluoroarenes.

Inexpensive and commercially available 2,4,6-triphenylpyrrolium tetrafluoroborate (TPT) is used as an organic photocatalyst for the nucleophilic aromatic substitution of unactivated fluoroarenes with pyrazole derivatives (SNAr) to form azole arenes. The use of organic photoredox catalysis enables the easy operation of this method under mild conditions. Various fluorinated aromatic compounds are suitable electrophiles for this transformation.

Seasonal heavy metal speciation in sediment and source tracking via Cu isotopic composition in Huangpu River, Shanghai, China.

The present study systematically analyzed and evaluated the variations in chemical speciation, pollution assessment, and source identification of heavy metals in sediments of Huangpu River. The methods employed included heavy metal concentration, chemical speciation and Cu isotopic compositions analysis. Results showed that the chemical speciation of sediment-bound heavy metals, characterized by significant seasonal variation, shifted from non-residual fractions dominating in spring and summer to residual fractions dominating in autumn and winter. Precipitation was identified as an important factor influencing the chemical speciation of sediment-bound heavy metals. Furthermore, ratio of the secondary phase to the primary phase, RSP (=Cnon-residual/Cresidual) values in Huangpu River sediments were higher than 1 in spring and summer, indicating that sediment-bound heavy metals in Huangpu River were mainly composed of non-residual fractions and could potentially be released into the river water. Principal component analysis (PCA) revealed that navigation, traffic, agricultural, and industrial activities could be the potential sources of heavy metal pollution. Notably, the δ65Cu values in Huangpu River sediments were observed to be isotopically lighter (from -0.37 to +0.18 ‰), suggesting that navigation might be the primary pollution source. These results will not only provide guidance in reducing heavy metal concentrations, but also serve as a crucial basis for policy making regarding heavy metal control.

[Effect of aerobic exercise on AKT/GSK3ß mediated hepatocyte apoptosis in nonalcoholic fatty liver disease].

OBJECTIVE: To investigate the effect of aerobic exercise on AKT/GSK3ß pathway-mediated hepatocyte apoptosis in non-alcoholic fatty liver diseases(NAFLD). METHODS: A total of 30 6-week-old male C57BL/6J mice, and mice were fed adaptively for one week. The control group was fed with ordinary diet, and the model group and model exercise group were fed with high-fat diet until 18 weeks. At the 10th week of the experiment, the model exercise group received aerobic exercise intervention for 8 consecutive weeks until the end of the experiment at the 18th week. Automatic biochemical analyzer to detect serum total cholesterol(TC), triglycerides(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) levels. Liver pathological morphology was observed by staining with oil red O and HE. The expression changes of AKT, P-AKT~( Ser473), GSK3ß, P-GSK3ß~(Ser9) and Caspase-3 proteins were detected by western blot, and the apoptosis of hepatocytes was detected by in situ terminal transferase labeling(TUNEL). RESULTS: (1) After intervention, compared with control group, body weight, liver index, serum TC, TG, ALT, AST and LDL-C levels in model group were significantly increased(P<0.01 or P<0.05), while HDL-C level was significantly decreased(P<0.01). Compared with model group, body weight, liver index, serum TC, TG, ALT, AST and LDL-C levels in model exercise group were significantly decreased(P<0.01 or P<0.05), while HDL-C level was significantly increased(P<0.01). (2) Compared with the control group, hepatocyte steatosis and the number of lipid droplets in model group were significantly increased. Compared with the model group, the degree of hepatic adipose degeneration was significantly improved and the number of hepatic lipid droplets was significantly decreased in the model exercise group. (3) Compared with control group, the protein expression levels of P-AKT~(Ser473) and P-GSK3ß~(Ser9) in model group were significantly decreased(P<0.01 or P<0.05), the protein expression levels of Caspase-3 were significantly increased(P<0.05), and the number of hepatocyte apoptosis was significantly increased(P<0.05). Compared with model group, the expression of P-AKT~(Ser473) and P-GSK3ß~(Ser9) protein in model exercise group was significantly increased(P<0.01 or P<0.05), the expression of Caspase-3 protein was significantly decreased(P<0.05), and the number of hepatocyte apoptosis was significantly decreased(P<0.01). CONCLUSION: Aerobic exercise can effectively improve NAFLD, by activating AKT/GSK3ß pathway and increasing the expression of AKT/GSK3ß pathway related molecules, thereby reducing caspase-3 expression and hepatocyte apoptosis.

Inflammatory Cytokine Interleukin-6 (IL-6) Promotes the Proangiogenic Ability of Adipose Stem Cells from Obese Subjects via the IL-6 Signaling Pathway.

BACKGROUND: The prevalence of obesity, as well as obesity-induced chronic inflammatory diseases, is increasing worldwide. Chronic inflammation is related to the complex process of angiogenesis, and we found that adipose-derived stem cells from obese subjects (obADSCs) had proangiogenic features, including higher expression levels of interleukin-6 (IL-6), Notch ligands and receptors, and proangiogenic cytokines, than those from control subjects. We hypothesized that IL-6 and Notch signaling pathways are essential for regulating the proangiogenic characteristics of obADSCs. OBJECTIVE: This study aimed to investigate whether the inflammatory cytokine interleukin 6 (IL-6) promotes the proangiogenic capacity of adipose stem cells in obese subjects via the IL-6 signaling pathway. METHODS: We compared the phenotype analysis as well as cell doubling time, proliferation, migration, differentiation, and proangiogenic properties of ADSCs in vitro. Moreover, we used small interfering RNAs to inhibit the gene and protein expression of IL-6. RESULTS: We found that ADSCs isolated from control individuals (chADSCs) and obADSCs had similar phenotypes and growth characteristics, and chADSCs had a stronger differentiation ability than obADSCs. However, obADSCs were more potent in promoting EA.hy926 cell migration and tube formation than chADSCs in vitro. We confirmed that IL-6 siRNA significantly reduced the transcriptional level of IL-6 in obADSCs, thereby reducing the expression of vascular endothelial growth factor (VEGF)- A, VEGF receptor 2, transforming growth factor ß, and Notch ligands and receptors in obADSCs. CONCLUSION: The finding suggests that inflammatory cytokine interleukin-6 (IL-6) promotes the proangiogenic ability of obADSCs via the IL-6 signaling pathway.

Quantitative prediction of the hydraulic performance of free water surface constructed wetlands by integrating numerical simulation and machine learning.

Quantitative prediction of the design parameter-influenced hydraulic performance is significant for optimizing free water surface constructed wetlands (FWS CWs) to reduce point and non-point source pollution and improve land utilization. However, owing to limitations of the test conditions and data scale, a quantitative prediction model of the hydraulic performance under multiple design parameters has not yet been established. In this study, we integrated field test data, mechanism model, statistical regression, and machine learning (ML) to construct such quantitative prediction models. A FWS CW numerical model was established by integrating 13 groups of trace data from field tests. Subsequently, training, test and extension datasets comprising 125 (5^3), 25 (L25(56)) and 16 (L16(44)) data points, respectively, were generated via numerical simulation of multi-level value combination of three quantitative design parameters, namely, water depth, hydraulic loading rate (HLR), and aspect ratio. The short circuit index (φ10), Morrill dispersion index (MDI), hydraulic efficiency (λ) and moment index (MI) were used as representative hydraulic performance indicators. Training set with large samples were analyzed to determine the variation rules of different hydraulic indicators. Based on the control variable method, φ10, λ, and MI grew exponentially with increasing aspect ratio whereas MDI showed a decreasing trend; with increasing water depth, φ10, λ, and MI showed polynomial decreases whereas MDI increased; with increasing HLR, φ10, λ, and MI slowly increased linearly whereas MDI showed the opposite trend. Finally, we constructed models based on multivariate nonlinear regression (MNLR) and ML (random forest (RF), multilayer perceptron (MLP), and support vector regression. The coefficients of determination (R2) of the MNLR and ML models fitting the training and test sets were all greater than 0.9; however, the generalization abilities of different models in the extension set were different. The most robust MLP, MNLR without interaction term, and RF models were recommended as the preferred models to hydraulic performance prediction. The extreme importance of aspect ratio in hydraulic performance was revealed. Thus, gaps in the current understanding of multivariate quantitative prediction of the hydraulic performance of FWS CWs are addressed while providing an avenue for researching FWS CWs in different regions according to local conditions.

DRR1 promotes neuroblastoma cell differentiation by regulating CREB expression.

BACKGROUND: Neuroblastoma is the most common cancer in infants and the most common extracranial solid tumor in childhood. DRR1 was identified to be downregulated in poorly differentiated ganglion cells from neuroblastoma model mice. However, the roles of DRR1 in neuroblastoma remain largely unclear. METHODS: The neuroblastoma cells were induced to differentiate, and the expression of DRR1 was detected. The expression of the neuroblastoma cell differentiation markers was analyzed in DRR1 shRNA- or DRR1-expressing vector-treated neuroblastoma cells. The downstream genes of DRR1 were screened with ChIP-seq assay. Finally, TNB1 cells were infected with DRR1 shRNA and CREB expressing vector containing lentivirus, and the expression of the cell differentiation markers, cell cycle distribution and tumor growth were analyzed. RESULTS: The expression of DRR1 was increased in differentiated neuroblastoma cells, and downregulation of DRR1 expression inhibited the differentiation of neuroblastoma cells. Further experiments indicated that CREB is a candidate downstream gene of DRR1, and it mediates neuroblastoma cell differentiation. Moreover, overexpression of CREB rescued the effect of DRR1 shRNA on cell differentiation, cell cycle distribution and tumor growth in neuroblastoma. CONCLUSIONS: DRR1-CREB axis modulates the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients. IMPACT: DRR1 is involved in regulation of the differentiation of neuroblastoma. Binding with actin is essential for DRR1 to regulate neuroblastoma cell differentiation. CREB is a candidate downstream gene of DRR1 in regulating of the differentiation of neuroblastoma.