ß-Ionone enhances the inhibitory effects of 5-fluorouracil on the proliferation of gastric adenocarcinoma cells by the GSK-3ß signaling pathway.

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.

Long-term effect of phenol, quinoline, and pyridine on nitrite accumulation in the nitrification process: performance, microbial community, metagenomics and molecular docking analysis.

Phenol, quinoline, and pyridine, commonly found in industrial wastewater, disrupt the nitrification process, leading to nitrite accumulation. This study explores the potential mechanisms through which these biotoxic organic compounds affect nitrite accumulation, using metagenomic and molecular docking analyses. Despite increasing concentrations of these compounds from 40 to 160 mg/L, ammonia nitrogen removal was not hindered, and stable nitrite accumulation rates exceeding 90 % were maintained. Additionally, these compounds inhibited nitrite-oxidizing bacteria (NOB) and enriched ammonia-oxidizing bacteria (AOB) in situ. As the concentration of these compounds rose, protein (PN) and polysaccharide (PS) concentrations also increased, along with a higher PN/PS ratio. Metagenomic analysis further revealed an increase in hao relative abundance, while microbial community analysis showed increased Nitrosomonas abundance, which contributed to nitrite accumulation stability. Molecular docking indicated that these compounds have lower binding energy with hydroxylamine oxidoreductase (HAO) and nitrate reductase (NAR), theoretically supporting the observed sustained nitrite accumulation.

High-temperature capacitive energy stroage in polymer nanocomposites through nanoconfinement.

Polymeric-based dielectric materials hold great potential as energy storage media in electrostatic capacitors. However, the inferior thermal resistance of polymers leads to severely degraded dielectric energy storage capabilities at elevated temperatures, limiting their applications in harsh environments. Here we present a flexible laminated polymer nanocomposite where the polymer component is confined at the nanoscale, achieving improved thermal-mechanical-electrical stability within the resulting nanocomposite. The nanolaminate, consisting of nanoconfined polyetherimide (PEI) polymer sandwiched between solid Al2O3 layers, exhibits a high energy density of 18.9 J/cm3 with a high energy efficiency of ~ 91% at elevated temperature of 200°C. Our work demonstrates that nanoconfinement of PEI polymer results in reduced diffusion coefficient and constrained thermal dynamics, leading to a remarkable increase of 37°C in glass-transition temperature compared to bulk PEI polymer. The combined effects of nanoconfinement and interfacial trapping within the nanolaminates synergistically contribute to improved electrical breakdown strength and enhanced energy storage performance across temperature range up to 250°C. By utilizing the flexible ultrathin nanolaminate on curved surfaces such as thin metal wires, we introduce an innovative concept that enables the creation of a highly efficient and compact metal-wired capacitor, achieving substantial capacitance despite the minimal device volume.

Identification and quantification of goat milk adulteration using mid-infrared spectroscopy and chemometrics.

The fraudulent adulteration of goat milk with cheaper and more available milk of other species such as cow milk is occurrence. The aims of the present study were to investigate the effect of goat milk adulteration with cow milk on the mid-infrared (MIR) spectrum and further evaluate the potential of MIR spectroscopy to identify and quantify the goat milk adulterated. Goat milk was adulterated with cow milk at 5 different levels including 10%, 20%, 30%, 40%, and 50%. Statistical analysis showed that the adulteration had significant effect on the majority of the spectral wavenumbers. Then, the spectrum was preprocessed with standard normal variate (SNV), multiplicative scattering correction (MSC), Savitzky-Golay smoothing (SG), SG plus SNV, and SG plus MSC, and partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLSR) were used to establish classification and regression models, respectively. PLS-DA models obtained good results with all the sensitivity and specificity over 0.96 in the cross-validation set. Regression models using raw spectrum obtained the best result, with coefficient of determination (R2), root mean square error (RMSE), and the ratio of performance to deviation (RPD) of cross-validation set were 0.98, 2.01, and 8.49, respectively. The results preliminarily indicate that the MIR spectroscopy is an effective technique to detect the goat milk adulteration with cow milk. In future, milk samples from different origins and different breeds of goats and cows should be collected, and more sophisticated adulteration at low levels should be further studied to explore the potential and effectiveness of milk mid-infrared spectroscopy and chemometrics.

Mechanocatalytic Hydrogen Generation in Centrosymmetric Barium Dititanate.

Novel phase of nano materials that break the traditional structural constraints are highly desirable, particularly in the field of mechanocatalysis, offering versatile applications ranging from energy to medical diagnosis and treatment. In this work, a distinct layered barium dititanate (BaTi2O5) nanocrystals using a pH-modulated hydrothermal method is successfully synthesized. These nanocrystals exhibit outstanding hydrogen generation capability (1160 µmol g-1 h-1 in pure water) and demonstrate remarkable performance in organic dye degradation using ultrasonication. The crystal structure of this newly discovered BaTi2O5 phase, is determined by a combination of synchrotron Powder Diffraction refinement and X-ray adsorption techniques, including X-ray Absorption Near Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS). Density Functional Theory calculations revealed that the newly-discovered BaTi2O5 phase demonstrates dipole moments along the z-axis, distributed in an antiparallel direction within a single unit cell. These inherent dipoles induce a surface polarization and a ferroelectric-flexoelectric response under mechanical stimuli when the materials go to nano dimension. With a band alignment well-suitable for hydrogen and reactive oxygen species generation, this BaTi2O5 phase demonstrates promising potential for Mechanocatalysis. The discovery of this distinct phase not only enriches the material candidates for mechanocatalysis but also provides valuable insights.

Novel Anoxic-Anaerobic-Oxic process successfully enriched anammox bacteria under actual municipal wastewater.

Anaerobic ammonia oxidation (Anammox) exhibits promise for wastewater treatment,but the enrichment of anammox bacteria (AnAOB) in municipal wastewater treatment plants is a significant challenge. This study constructed a novel Anoxic-Anaerobic-Oxic (AAnO) process with a pure biofilm anoxic zone fed with actual fluctuating municipal wastewater and operated for six months to enrich AnAOB at ambient temperature. High-throughput sequencing (HTS), qPCR, and fluorescence in situ hybridization showed that AnAOB were successfully enriched in the anoxic biofilms, reaching 1.56 % relative abundance on day 75 detected by HTS. During the period from day 130 to day 186, the anammox process contributed to 55.8 ± 19.2 % of the nitrogen removal in the anoxic zone. Phylogenetic analysis revealed this AnAOB species was closely related to Candidatus Brocadia fulgida. This study provides technical support for the application of anammox in mainstream wastewater.

Phenotypic and Genetic Analyses of Mastitis, Endometritis, and Ketosis on Milk Production and Reproduction Traits in Chinese Holstein Cattle.

Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60-1.50 d), Interval from First Service to Conception (FSTC, 0.20-16.20 d), Calving Interval (CI, 4.00-7.00 d), and Number of Services (NUMS, 0.07-0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding.

A High-Carbohydrate Diet Induces Cognitive Impairment and Promotes Amyloid Burden and Tau Phosphorylation via PI3K/Akt/GSK-3ß Pathway in db/db Mice.

BACKGROUND: Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear. METHODS: The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated. RESULTS: Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-ß burden and expression of ß-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3ß pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD. CONCLUSIONS: Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

A highly polarizable concentrated dipole glass for ultrahigh energy storage.

Relaxor ferroelectrics are highly desired for pulse-power dielectric capacitors, however it has become a bottleneck that substantial enhancements of energy density generally sacrifice energy efficiency under superhigh fields. Here, we demonstrate a novel concept of highly polarizable concentrated dipole glass in delicately-designed high-entropy (Bi1/3Ba1/3Na1/3)(Fe2/9Ti5/9Nb2/9)O3 ceramic achieved via substitution of multiple heterovalent ferroelectric-active principal cation species on equivalent lattice sites. The atomic-scaled polar heterogeneity of dipoles with different polar vectors between adjacent unit cells enables diffuse reorientation process but disables appreciable growth with electric fields. These unique features cause superior recoverable energy density of ~15.9 J cm-3 and efficiency of ~93.3% in bulk ceramics. We also extend the highly polarizable concentrated dipole glass to the prototype multilayer ceramic capacitor, which exhibits record-breaking recoverable energy density of ~26.3 J cm-3 and efficiency of ~92.4% with excellent temperature and cycle stability. This research presents a distinctive approach for designing high-performance energy-storage dielectric capacitors.

Ultra-Weak Polarization-Strain Coupling Effect Boosts Capacitive Energy Storage.

In pulse power systems, multilayer ceramic capacitors (MLCCs) encounter significant challenges due to the heightened loading electric field (E), which can lead to fatigue damage and ultrasonic concussion caused by electrostrictive strain. To address these issues, an innovative strategy focused on achieving an ultra-weak polarization-strain coupling effect is proposed, which effectively reduces strain in MLCCs. Remarkably, an ultra-low electrostrictive coefficient (Q33) of 0.012 m4 C-2 is achieved in the composition 0.55(Bi0.5Na0.5)TiO3-0.45Pb(Mg1/3Nb2/3)O3, resulting in a significantly reduced strain of 0.118% at 330 kV cm-1. At the atomic scale, the local structural heterogeneity leads to an expanded and loose lattice structure, providing ample space for large ionic displacement polarization instead of lattice stretching when subjected to the applied E. This unique behavior not only promotes energy storage performance (ESP) but also accounts for the observed ultra-low Q33 and strain. Consequently, the MLCC device exhibits an impressive energy storage density of 14.6 J cm-3 and an ultrahigh efficiency of 93% at 720 kV cm-1. Furthermore, the superior ESP of the MLCC demonstrates excellent fatigue resistance and temperature stability, making it a promising solution for practical applications. Overall, this pivotal strategy offers a cost-effective solution for state-of-the-art MLCCs with ultra-low strain-vibration in pulse power systems.

Defect dipole stretching enables ultrahigh electrostrain.

Piezoelectric actuators have been extensively utilized as micro-displacement devices because of their advantages of large output displacement, high sensitivity, and immunity to electromagnetic interference. Here, we propose a straightforward approach to design <110>-oriented defect dipoles by introducing A-site vacancies and oxygen vacancies in (K0.48Na0.52)0.99NbO2.995 ceramics. As a result, we achieve ultrahigh electrostrains of 0.7% at 20 kV cm-1 (with an effective piezoelectric strain coefficient d33* = 3500 pm V-1), outperforming the performance of existing piezoelectric ceramics at the same driving field. The exceptional electrostrain is primarily attributed to the large stretching of defect dipoles when subjected to an applied electric field, a phenomenon that has been experimentally confirmed. Moreover, the strong interaction between these defect dipoles and <110> spontaneous polarizations plays a critical role in minimizing hysteresis and ensuring excellent fatigue resistance. Our findings present a practical and effective strategy for developing high-performance piezoelectric materials tailored for advanced actuator applications.

Partitioning polar-slush strategy in relaxors leads to large energy-storage capability.

Relaxor ferroelectric (RFE) films are promising energy-storage candidates for miniaturizing high-power electronic systems, which is credited to their high energy density (Ue) and efficiency. However, advancing their Ue beyond 200 joules per cubic centimeter is challenging, limiting their potential for next-generation energy-storage devices. We implemented a partitioning polar-slush strategy in RFEs to push the boundary of Ue. Guided by phase-field simulations, we designed and fabricated high-performance Bi(Mg0.5Ti0.5)O3-SrTiO3-based RFE films with isolated slush-like polar clusters, which were realized through suppression of the nonpolar cubic matrix and introduction of highly insulating networks. The simultaneous enhancement of the reversible polarization and breakdown strength leads to a Ue of 202 joules per cubic centimeter with a high efficiency of ~79%. The proposed strategy provides a design freedom for next-generation high-performance dielectrics.

Optimizing high-temperature energy storage in tungsten bronze-structured ceramics via high-entropy strategy and bandgap engineering.

As a vital material utilized in energy storage capacitors, dielectric ceramics have widespread applications in high-power pulse devices. However, the development of dielectric ceramics with both high energy density and efficiency at high temperatures poses a significant challenge. In this study, we employ high-entropy strategy and band gap engineering to enhance the energy storage performance in tetragonal tungsten bronze-structured dielectric ceramics. The high-entropy strategy fosters cation disorder and disrupts long-range ordering, consequently regulating relaxation behavior. Simultaneously, the reduction in grain size, elevation of conductivity activation energy, and increase in band gap collectively bolster the breakdown electric strength. This cascade effect results in outstanding energy storage performance, ultimately achieving a recoverable energy density of 8.9 J cm-3 and an efficiency of 93% in Ba0.4Sr0.3Ca0.3Nb1.7Ta0.3O6 ceramics, which also exhibit superior temperature stability across a broad temperature range up to 180 °C and excellent cycling reliability up to 105. This research presents an effective method for designing tetragonal tungsten bronze dielectric ceramics with ultra-high comprehensive energy storage performance.

Electrical de-poling and re-poling of relaxor-PbTiO3 piezoelectric single crystals without heat treatment.

Re-poling of unexpected partially depoled piezoelectric materials conventionally needs to be first fully depoled through annealing above their Curie temperature to revive piezoelectric performances. Here, we investigated de-poling and re-poling of Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystals under electric fields at room temperature. We found that alternating current electric fields with amplitudes near the coercive field at low frequencies (<10 Hz) can be employed to successfully depolarize poled crystals at room temperature. We also demonstrated a reversible polarization switching process with a relaxor-PbTiO3 single crystal ultrasound transducer without device performance degradations. This experimental observation is supported by phase-field simulation, showing that alternating current electric fields can readily induce de-poling at room temperature, while direct current electric fields induce a transient depoled state only within an uncontrollable short period of time. The findings suggest new strategies for unprecedented in-device tailoring of the polarization states of ferroelectric materials.

Unilateral biportal endoscopic decompression versus anterior cervical decompression and fusion for unilateral cervical radiculopathy or coexisting cervical myelopathy: a prospective, randomized, controlled, noninferiority trial.

BACKGROUND: Cervical spondylosis (CS), including myelopathy and radiculopathy, is the most common degenerative cervical spine disease. This study aims to evaluate the clinical outcomes of unilateral biportal endoscopy (UBE) compared to those of conventional anterior cervical decompression and fusion (ACDF) for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. METHODS: A prospective, randomized, controlled, noninferiority trial was conducted. The sample consisted of 131 patients who underwent UBE or ACDF was conducted between September 2021 and September 2022. Patients with cervical nerve roots or coexisting spinal cord compression symptoms and imaging-defined unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs were randomized into two groups: a UBE group (n = 63) and an ACDF group (n = 68). The operative time, blood loss, length of hospital stay after surgery, and perioperative complications were recorded. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) scale scores, visual analog scale (VAS) scores, neck disability index (NDI) scores, and recovery rate (RR) of the mJOA were utilized to evaluate clinical outcomes. RESULTS: The hospital stay after surgery was significantly shorter in patients treated with UBE than in those treated with ACDF (p < 0.05). There were no significant differences in the neck or arm VAS score, NDI score, mJOA score, or mean RR of the mJOA between the two groups (p < 0.05). Only mild complications were observed in both groups, with no significant difference (p = 0.30). CONCLUSION: UBE can significantly relieve pain and disability without severe complications, and most patients are satisfied with this technique. Consequently, this procedure can be used safely and effectively as an alternative to ACDF for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 02/08/2023 ( http://www.chictr.org.cn , #ChiCTR2300074273).

Exploring transformation of dissolved organic matters and dissolved organic nitrogen in full-scale anammox wastewater treatment: Temperature and microbial roles.

Variation of dissolved organic matters (DOM) in mainstream anammox process has received limited attention. This study systematically characterized DOM and dissolved organic nitrogen (DON) in a full-scale mainstream anammox wastewater treatment plant (WWTP) using spectroscopy and Fourier transform-ion cyclotron resonance mass spectrometry. Roles of bacterial community structures related with temperatures on DOM and DON transformations were analyzed. Results indicated that the WWTP removed highly bioavailable, S-containing DOM while producing more unsaturated, aromatic, and N-containing DOM. Higher relative abundances of Proteobacteria and Chloroflexi at low temperature resulted in greater removal rates of proteins, SMP-like and humic acid-like substances. At high temperature, higher relative abundance of Actinobacteriota increased lignin production. Principal component analysis revealed that temperature significantly impacted DOM characteristics compared to DON. These findings are crucial for understanding DOM and DON transformation during mainstream anammox WWTP.

Treatment of low-C/N nitrate wastewater using a partial denitrification-anammox granule system: Granule reconstruction, stability, and microbial structure analyses.

Industrial wastewater discharged into sewer systems is often characterized by high nitrate contents and low C/N ratios, resulting in high treatment costs when using conventional activated sludge methods. This study introduces a partial denitrification-anammox (PD/A) granular process to address this challenge. The PD/A granular process achieved an effluent TN level of 3.7 mg/L at a low C/N ratio of 2.3. Analysis of a typical cycle showed that the partial denitrification peaked within 15 min and achieved a nitrate-to-nitrite transformation ratio of 86.9%. Anammox, which was activated from 15 to 120 min, contributed 86.2% of the TN removal. The system exhibited rapid recovery from post-organic shock, which was attributed to significant increases in protein content within TB-EPS. Microbial dispersion and reassembly were observed after coexistence of the granules, with Thauera (39.12%) and Candidatus Brocadia (1.25%) identified as key functional microorganisms. This study underscores the efficacy of PD/A granular sludge technology for treating low-C/N nitrate wastewater.

Rapid detection and quantification of melamine, urea, sucrose, water, and milk powder adulteration in pasteurized milk using Fourier transform infrared (FTIR) spectroscopy coupled with modern statistical machine learning algorithms.

There is an evident requirement for a rapid, efficient, and simple method to screen the authenticity of milk products in the market. Fourier transform infrared (FTIR) spectroscopy stands out as a promising solution. This work employed FTIR spectroscopy and modern statistical machine learning algorithms for the identification and quantification of pasteurized milk adulteration. Comparative results demonstrate modern statistical machine learning algorithms will improve the ability of FTIR spectroscopy to predict milk adulteration compared to partial least square (PLS). To discern the types of substances utilized in milk adulteration, a top-performing multiclassification model was established using multi-layer perceptron (MLP) algorithm, delivering an impressive prediction accuracy of 97.4 %. For quantification purposes, bayesian regularized neural networks (BRNN) provided the best results for the determination of both melamine, urea and milk powder adulteration, while extreme gradient boosting (XGB) and projection pursuit regression (PPR) gave better results in predicting sucrose and water adulteration levels, respectively. The regression models provided suitable predictive accuracy with the ratio of performance to deviation (RPD) values higher than 3. The proposed methodology proved to be a cost-effective and fast tool for screening the authenticity of pasteurized milk in the market.

Deletion of GPR81 activates CREB/Smad7 pathway and alleviates liver fibrosis in mice.

BACKGROUND: Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis. METHODS: The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-ß1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-ß1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation. RESULTS: CCl4 exposure or TGF-ß1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-ß1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-ß1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs. CONCLUSION: GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.

Novel separate aeration self-circulating technology for continuous aerobic granular sludge process: Performance evaluation, hydrodynamic simulation and control strategy.

The continuous aerobic granular sludge (AGS) process is promising for upgrading existing wastewater treatment facilities. However, this approach is still challenging because of its complicated structure and operation. To address this issue, a novel separate aeration self-circulating technology (abbreviated as Zier) was proposed, which is promising for cultivating AGS by its outstanding upflow velocity and circulation multiplier (more than 30 m/h and 200, respectively). This study elaborated on the Zier reactor's feasibility, optimization, and control strategy through computational fluid dynamics simulations, theoretical calculations, and experiments. An appropriate flow regime for efficient removal of pollutant and granulation of sludge was attained at a superficial gas velocity of 1.3 cm/s. Moreover, optimizing the aeration column diameter to half of the reaction column and increasing the height/diameter ratio to 20 dramatically boosted the nitrogen removal capacity over 1.6 kg N/m3/d. Utilizing a smaller circulation pipe diameter ensured granulation under a consistent flow regime. By judiciously regulating, multiple CSTRs and PFRs seamlessly integrated within the Zier reactor across a broad spectrum of particle sludge. The validity of these findings was further substantiated through experimental and theoretical validations. Drawing from these findings, a multi-scenario control strategy was proposed as Zier's map. With all the superiorities shown by the Zier reactor, this study could offer new insights into an efficient continuous AGS process.