Artificial neural network optimisation of natural deep eutectic solvent extraction process of Danshen-Gegen and cytotoxicity study.

Natural deep eutectic solvents (NaDESs) are environmentally friendly and efficient for the componential extraction of traditional Chinese medicine compared to conventional organic solvents. In this study, NaDES was screened and employed to extract Danshen-Gegen (DG), and the extraction process was optimised by response surface methodology (RSM) and artificial neural networks (ANN) model. Besides, the in vitro security of extracts of DG were evaluated in PC12 cells. As a result, Betaine-Urea (Bet-Ur) was screened as extraction solvent and ANN model was more accurate than RSM model in optimising the extraction parameter. The extraction process optimised by ANN was as follows: 70% NaDES concentration, 80 mg/mL solid to liquid ratio, 67 °C ultrasonic temperature, and 33 min of ultrasonic time. The comprehensive value of extraction yield was 0.7251 ± 0.84%. IC50 of Bet-Ur, NaDES DG extract and aqueous DG extract were 0.15%, 0.3% and 10% (v/v).

STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

Dexmedetomidine attenuates sleep deprivation-induced inhibition of hippocampal neurogenesis via VEGF-VEGFR2 signaling and inhibits neuroinflammation.

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 µg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.

Reducing complement activation during sleep deprivation yields cognitive improvement by dexmedetomidine.

BACKGROUND: Sleep loss and its associated conditions (e.g. cognitive deficits) represent a large societal burden, but the underlying mechanisms of these cognitive deficits remain unknown. This study assessed the effect of dexmedetomidine (DEX) on cognitive decline induced by sleep loss. METHODS: C57BL/6 mice were subjected to chronic sleep restriction (CSR) for 20 h (5 pm-1 pm the next day) daily for 7 days, and cognitive tests were subsequently carried out. The neuromolecular and cellular changes that occurred in the presence and absence of DEX (100 µg kg-1, i.v., at 1 pm and 3 pm every day) were also investigated. RESULTS: CSR mice displayed a decline in learning and memory by 12% (P<0.05) in the Y-maze and by 18% (P<0.01) in the novel object recognition test; these changes were associated with increases in microglial activation, CD68+ microglial phagosome counts, astrocyte-derived complement C3 secretion, and microglial C3a receptor expression (all P<0.05). Synapse elimination, as indicated by a 66% decrease in synaptophysin expression (P=0.0004) and a 45% decrease in postsynaptic density protein-95 expression (P=0.0003), was associated with the occurrence of cognitive deficits. DEX activated astrocytic α2A adrenoceptors and inhibited astrocytic complement C3 release to attenuate synapse elimination through microglial phagocytosis. DEX restored synaptic connections and reversed cognitive deficits induced by CSR. CONCLUSIONS: The results demonstrate that complement pathway activation associated with synapse elimination contributes to sleep loss-related cognitive deficits and that dexmedetomidine protects against sleep deprivation-induced complement activation. Dexmedetomidine holds potential for preventing cognitive deficits associated with sleep loss, which warrants further study.

High-power femtosecond regenerative amplifier based on Yb:CaYAlO4 dual-crystal configuration.

A thermal lens insensitive regenerative amplifier (RA) with a dual Yb:CaYAlO4 (Yb:CYA) crystal configuration for extending gain spectra is demonstrated for the first time, to the best of our knowledge. By orthogonalizing the orientation of two a-cut Yb:CYA crystals in one RA, the Q switched spectrum with a full width at half maximum of 15.4 nm is generated, which is 1.5 and 1.6 times of the Q switched spectral bandwidth with π- and σ-polarization, respectively. With chirped pulses injection, this RA can deliver laser pulses with an average power exceeding 10 W at the repetition rate of 20-800 kHz and pulse energy of 1.5 mJ at 1 kHz. This is the highest average power from the Yb:CYA RA to the best of our knowledge. Finally, compressed pulses of 163 fs with 92% overall efficiency are realized. Thanks to the heat insensitive cavity design and excellent thermodynamic properties of the Yb:CYA crystal, the output laser beam is close to the diffraction limit with an M2 value of 1.07 × 1.07.

CD33/TREM2 Signaling Mediates Sleep Deprivation-Induced Memory Impairment by Regulating Microglial Phagocytosis.

Sleep deprivation causes significant memory impairment in healthy adults. Extensive research has focused on identifying the biological mechanisms underlying memory impairment. Microglia-mediated synaptic elimination plays an indispensable role in sleep deprivation. Here, the potential role of the CD33/TREM2 signaling pathway in modulating memory decline during chronic sleep restriction (CSR) was evaluated. In this study, adult male C57BL/6 mice were sleep-restricted using an automated sleep deprivation apparatus for 20 h per day for 7 days. The Y-maze test revealed that spontaneous alternation was significantly reduced in CSR mice compared with control mice. The percentage of exploratory preference for the novel object in CSR mice was significantly decreased compared with that in control mice. These memory deficits correlated with aberrant microglial activation and increased phagocytic ability. Moreover, in CSR mice, the CD33 protein level in hippocampal tissue was significantly downregulated, but the TREM2 protein level was increased. In BV2 microglial cells, downregulation of CD33 increased TREM2 expression and improved microglial phagocytosis. Then, the sialic ligand monosialo-ganglioside 1 (GM1, 20 mg/kg, i.p.) was administered to mice once a day during CSR. Our results further showed that GM1 activated CD33 and consequently disturbed TREM2-mediated microglial phagocytosis. Finally, GM1 reversed CSR-induced synaptic loss and memory impairment via the CD33/TREM2 signaling pathway in the CA1 region of the hippocampus. This study provides novel evidence that activating CD33 and/or inhibiting TREM2 activity represent potential therapies for sleep loss-induced memory deficits through the modulation of microglial phagocytosis.

Temporal contrast enhancement via nonlinear elliptical polarization rotation in a solid thin plate.

We demonstrate the simultaneous temporal contrast enhancement and spectral broadening via nonlinear elliptical polarization rotation in a solid thin plate. The efficiency, temporal contrast enhancement, spectral broadening, pulse compression and power stability are experimentally investigated. With this simple and efficient scheme, the temporal cleaned pulses with energy of 325 µJ and total efficiency of 30% are obtained. The temporal contrast and spectral bandwidth of the filtered pulse are 1011 and 104 nm, respectively. The pulse compressed from 180 fs to 45.8 fs is realized by utilizing chirped mirrors, corresponding to a compression factor of 3.93. With stable output power, presented scheme could be implemented in the ultra-intense femtosecond laser facilities.

Generation of 56.5 W femtosecond laser radiation by the combination of an Nd-doped picosecond amplifier and multi-pass-cell device.

We demonstrate the generation of high average power femtosecond laser radiation by combination of an Nd-doped picosecond amplifier and a multi-pass cell device. With this efficient and robust scheme, the pulse duration of a picosecond amplifier is compressed from 9.13 ps to 477 fs, corresponding to a compression factor of 19.1. The average power before and after pulse compression is 77 W and 56.5 W respectively, so the overall transmission reaches 73.4%. The presented scheme offers a viable route toward low-cost and simple configuration high power femtosecond lasers driven by Nd-doped picosecond amplifiers.

Therapeutic targeting of STING-TBK1-IRF3 signalling ameliorates chronic stress induced depression-like behaviours by modulating neuroinflammation and microglia phagocytosis.

Stress is well known to contribute to the development of both neurological and psychiatric diseases. In the central nervous system, a role for STING (stimulator of interferon genes) in modulating immunological responses has been widely suggested, and this protein possesses both neurotoxic and neuroprotective properties. However, the potential role of the STING signalling pathway and the underlying regulatory mechanism in chronic stress have not been well established. In this study, C57BL/6 mice were subjected to intermittent restraint stress for 14 days (6 h/day), and sucrose preference, elevated plus maze, and tail suspension tests were performed by mice subjected to chronic restraint stress (RST). Here, we showed that RST mice displayed depression-like behaviours, accompanied by increased levels of proinflammatory cytokines in the brain. We also observed remarkably decreased levels of the pathway components STING, p-TBK1 (phospho-TANK-binding kinase-1), and p-IRF3 (phospho-interferon regulatory factor-3) in the hippocampus and the prefrontal cortex of RST mice. Significant reductions in STING fluorescence intensity were also observed in the hippocampus and the prefrontal cortex of RST mice. Next, fluorescently labelled latex beads, flow cytometry, and CD68-positive cell counts were utilized to evaluate the phagocytic abilities of microglia in vivo and in vitro. Importantly, our results first indicated that activation of the STING pathway by administration of the STING agonist 2'3-cGAMP enhanced microglial phagocytosis and suppressed the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in the brains of RST mice, which further led to antidepressant effects. Based on the results of our study, the amelioration of stress-driven depression-like behaviours by activation of the STING pathway is associated with the suppression of neuroinflammation and enhanced phagocytosis.

Fabrication of an antifouling PES ultrafiltration membrane via blending SPSF.

Sulfonated polysulfone (SPSF) with different sulfonation degrees (10%, 30%, and 50%) was added to polyethersulfone (PES) to improve the separation and antifouling performance of polyethersulfone ultrafiltration membranes. The PES/SPSF blend ultrafiltration membrane was prepared by the non-solvent induced phase inversion method (NIPS), and the effect of sulfonation degree on the ultrafiltration performance was studied. The compatibility of SPSF and PES was calculated by the group contribution method, and confirmed by differential scanning calorimetry (DSC). The morphology and surface roughness of the membrane were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), the chemical composition of the membrane was analyzed by X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (FTIR), and the permeability and anti-fouling performance of the blend membrane were studied through filtration experiments. The research shows that the flux and anti-fouling performance of the blend membrane have been improved after adding SPSF. When the sulfonation degree of the SPSF is 30%, the pure water flux of the blend membrane can reach 530 L m-2 h-1, the rejection rate of humic acid (HA) is 93%, the flux recovery rate of HA increases from 69.23% to 79.17%, and the flux recovery rate of BSA increases from 72.56% to 83%.

Involvement of Paired Immunoglobulin-like Receptor B in Diabetes-Associated Cognitive Dysfunction Through Modulation of Axon Outgrowth and Dendritic Remodeling.

Type 2 diabetic patients have high risk of developing cognitive dysfunction, in which neural structural plasticity has played a pivotal role. Paired immunoglobulin-like receptor B (PirB), a receptor mainly expressed in neurons, acts as a critical inhibitor of neurite outgrowth and neural plasticity. However, the role of PirB in type 2 diabetes-associated cognitive dysfunction remains unknown. In this study, learning and memory impairment was observed in 24-week-old db/db mice by performing Morris water maze task, and the number of synapses along with the length of postsynaptic density by transmission electron microscopy were reduced in the hippocampus of db/db mice. Furthermore, PirB expression in the hippocampus of db/db mice was significantly upregulated using western blotting and immunofluorescence analysis. In cultured hippocampal neurons, high glucose treatment reduced the length of the longest neurite as well as axon initial segment (AIS), whereas silencing PirB expression rescued high glucose-induced neurite outgrowth inhibition, but not AIS. Additionally, cognitive deficits, dendrite morphology defects, and synapse-related proteins loss in db/db mice were alleviated when PirB knockdown was performed by adeno-associated virus injection. In conclusion, PirB is involved in diabetes-associated cognitive dysfunction through modulation of axon outgrowth and dendritic remodeling, providing a potential therapeutic target for diabetes-associated cognitive dysfunction.

The inhibition of NFкB signaling and inflammatory response as a strategy for blunting bile acid-induced hepatic and renal toxicity.

The cholestatic liver injury could occur in response to a variety of diseases or xenobiotics. Although cholestasis primarily affects liver function, it has been well-known that other organs such as the kidney could be influenced in cholestatic patients. Severe cholestasis could lead to tissue fibrosis and organ failure. Unfortunately, there is no specific therapeutic option against cholestasis-induced organ injury. Hence, finding the mechanism of organ injury during cholestasis could lead to therapeutic options against this complication. The accumulation of potentially cytotoxic compounds such as hydrophobic bile acids is the most suspected mechanism involved in the pathogenesis of cholestasis-induced organ injury. A plethora of evidence indicates a role for the inflammatory response in the pathogenesis of several human diseases. Here, the role of nuclear factor-kB (NFkB)-mediated inflammatory response is investigated in an animal model of cholestasis. Bile duct ligated (BDL) animals were treated with sulfasalazine (SSLZ, 10 and 100 mg/kg, i.p) as a potent inhibitor of NFkB signaling. The NFkB proteins family activity in the liver and kidney, serum and tissue levels of pro-inflammatory cytokines, tissue biomarkers of oxidative stress, serum markers of organ injury, and the liver and kidney histopathological alterations and fibrotic changes. The oxidative stress-mediated inflammatory-related indices were monitored in the kidney and liver at scheduled time intervals (3, 7, and 14 days after BDL operation). Significant increase in serum and urine markers of organ injury, besides changes in biomarkers of oxidative stress and tissue histopathology, were evident in the liver and kidney of BDL animals. The activity of NFkB proteins (p65, p50, p52, c-Rel, and RelB) was significantly increased in the liver and kidney of cholestatic animals. Serum and tissue levels of pro-inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-7, IL-12, IL-17, IL-18, IL-23, TNF-α, and INF-γ) were also higher than sham-operated animals. Moreover, TGF- ß, α-SMA, and tissue fibrosis (Trichrome stain) were evident in cholestatic animals' liver and kidneys. It was found that SSLZ (10 and 100 mg/kg/day, i.p) alleviated cholestasis-induced hepatic and renal injury. The effect of SSLZ on NFkB signaling and suppression of pro-inflammatory cytokines could play a significant role in its protective role in cholestasis. Based on these data, NFkB signaling could receive special attention to develop therapeutic options to blunt cholestasis-induced organ injury.

Fabrication of a hybrid ultrafiltration membrane based on MoS2 modified with dopamine and polyethyleneimine.

The hydrophobicity of ultrafiltration membranes is the main cause of membrane fouling and reduced permeability, so it is necessary to improve the hydrophilicity and anti-fouling performance of ultrafiltration membrane materials. MoS2 nanoparticles that were modified with polydopamine (PDA) and polyethyleneimine (PEI), named MoS2-PDA-PEI, were added to fabricate a polyethersulfone ultrafiltration membrane (PES/MoS2-PDA-PEI) for the first time. The effects of modified MoS2 nanoparticles on membrane performance were clarified. The results indicated that the permeability, rejection, and anti-fouling capability of the hybrid PES/MoS2-PDA-PEI membrane have been improved compared with the pristine PES membrane. When the content of MoS2-PDA-PEI nanoparticles in the membrane is 0.5%, the pure water flux of the hybrid membrane reaches 364.03 L m-2 h-1, and the rejection rate of bovine serum albumin (BSA) and humic acid (HA) is 96.5% and 93.2% respectively. The flux recovery rate of HA reached 97.06%. As expected, the addition of MoS2-PDA-PEI nanoparticles promotes the formation of the porous structure and improves the hydrophilicity of the membrane, thereby improving its antifouling performance.

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

BACKGROUND: Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases. METHODS: A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules. DISCUSSION: We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03651986.

Comprehensive Application of Autologous Costal Cartilage Grafts in Rhino- and Mentoplasty.

BACKGROUND: Underdevelopment of nose and chin in East Asians is quite common. Rhinoplasty and mentoplasty are effective procedures to solve the above-depicted defects and can achieve remarkable cosmetic effects. An autologous costal cartilage graft has become an ideal material for rhinoplasty, especially for revision surgery. However, many problems in the clinical application of costal cartilage remain unresolved. This study is to investigate application strategies of autologous costal cartilage grafts in rhino- and mentoplasty. METHODS: The methods involved are as follows: application of an integrated cartilage scaffold; comprehensive application of diced cartilage; and chin augmentation of an autologous costal cartilage graft. RESULTS: In this study, satisfactory facial contour appearance was immediately achieved in 28 patients after surgery; 21 patients had satisfactory appearance of the nose and chin during the 6- to 18-month follow-up. Cartilage resorption was not observed. Two patients had nasal tip skin redness and were cured after treatment. CONCLUSION: This procedure can be used to effectively solve: curvature of the costal cartilage segment itself; warping of the carved costal cartilage; and effective use of the costal cartilage segment. The procedure has achieved satisfactory outcomes, and its application is worth extending to clinical practice.

Stokes Shift and Specific Fluorescence as Potential Indicators of Organic Matter Hydrophobicity and Molecular Weight in Membrane Bioreactors.

Hydrophobicity and molecular weight (MW) are two fundamental properties of dissolved organic matter (DOM) in wastewater treatment systems. This study proposes fluorescence Stokes shift and specific fluorescence intensity (SFI) as novel indicators of hydrophobicity and MW. These indicators originate from the energy gap and photon efficiency of the fluorescence process and can be readily extracted from a fluorescence excitation-emission matrix (EEM). The statistical linkages between these indicators and hydrophobicity/MW were explored through investigation of DOM across 10 full-scale membrane bioreactors treating municipal wastewater. Stokes shift was found to exhibit a general rule among the hydrophobicity components in the order of hydrophilic substances (HIS) < hydrophobic acids (HOA) < hydrophobic bases (HOB). The Stokes shift of 1.2 µm-1 is a critical border, above which the relative fluorescence correlated significantly with the HOA-related content (Pearson's r = 0.8). With regard to MW distribution (<1, 1-10, 10-100, and >100 kDa), SFI was found to be the most sensitive to the change of MW of <1 kDa proportion, especially at the excitation/emission wavelengths of 200-320/310-550 nm (r > 0.9). Hydrophobicity-related π conjugation and MW-dependent light exposure might be responsible for the correlations. These fluorescence indicators may be useful for convenient monitoring of DOM in wastewater treatment systems.

Association between certain non-small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death-ligand 1 inhibition.

This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and ß-tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild-type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild-type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower ß-tubulin III expression. In addition, wild-type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD-L1 high expression. As a pilot validation, 21 wild-type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo-regimen where targeted therapy has not been a routine option. Further validation is warranted.

Reducing aeration energy consumption in a large-scale membrane bioreactor: Process simulation and engineering application.

Reducing the energy consumption of membrane bioreactors (MBRs) is highly important for their wider application in wastewater treatment engineering. Of particular significance is reducing aeration in aerobic tanks to reduce the overall energy consumption. This study proposed an in situ ammonia-N-based feedback control strategy for aeration in aerobic tanks; this was tested via model simulation and through a large-scale (50,000 m(3)/d) engineering application. A full-scale MBR model was developed based on the activated sludge model (ASM) and was calibrated to the actual MBR. The aeration control strategy took the form of a two-step cascaded proportion-integration (PI) feedback algorithm. Algorithmic parameters were optimized via model simulation. The strategy achieved real-time adjustment of aeration amounts based on feedback from effluent quality (i.e., ammonia-N). The effectiveness of the strategy was evaluated through both the model platform and the full-scale engineering application. In the former, the aeration flow rate was reduced by 15-20%. In the engineering application, the aeration flow rate was reduced by 20%, and overall specific energy consumption correspondingly reduced by 4% to 0.45 kWh/m(3)-effluent, using the present practice of regulating the angle of guide vanes of fixed-frequency blowers. Potential energy savings are expected to be higher for MBRs with variable-frequency blowers. This study indicated that the ammonia-N-based aeration control strategy holds promise for application in full-scale MBRs.