Fluoxetine Research Articles

Fenton pretreatment to mitigate membrane distillation fouling during treatment of landfill leachate membrane concentrate: Performance and mechanism

Membrane distillation (MD) is regarded as a promising technology for treatment of landfill leachate membrane concentrate (LLMC) due to its merits of low cost and high rejection of non-volatile components. However, the high concentration of pollutants in the wastewater will cause severe membrane fouling, resulting in costly cleaning and maintenance. In this study, Fenton pretreatment was applied to alleviate membrane fouling during MD treatment of LLMC. Compared to rapid flux decline of 88.2% at concentration factor (CF) of 3 for raw LLMC, MD flux only decreased by 17.4% at CF = 6 for treating acidic Fenton effluent without subsequent pH adjustment (Fe2+ and H2O2 concentration were 600 mg/L and 1457 mg/L, respectively). The pH neutralization of Fenton effluent or merely acidification of LLMC could not achieve such excellent fouling mitigation. It was concluded that both oxidation and acidification were critical and the collaboration mechanism was revealed to explain low membrane fouling. Firstly, Fenton oxidation removed organic contaminants, reduced the hydrophobicity of organic substances and increased the percentage of carboxylic group within LLMC. Thus, hydrophobic (HP) attraction was weakened but multivalent cation bridging became dominant fouling mechanism for neutral Fenton effluent. Then, acidification weakened multivalent cation bridging by inhibiting the deprotonation of carboxylic group, further mitigating membrane fouling. However, acidification of LLMC caused more severe organic fouling due to decrease in electrostatic (EL) repulsion. In addition to low membrane fouling, satisfactory total organic carbon (TOC) rejection rate of 96.23% was achieved during combined Fenton-MD process. This study demonstrated that Fenton pretreatment without pH neutralization could effectively alleviate MD fouling and elucidated the synergistic mechanism between oxidation and acidification for fouling mitigation.

The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats

BackgroundDepression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. ResultsThe results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. ConclusionAcupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.

Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy

Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P=.001); and those with AF saw worse disease progression (hazard ratio, 1.54; P=.03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.

Antidepressants and their metabolites primarily affect lysosomal functions in the marine mussel, Mytilus galloprovincialis

Antidepressants widely occur as emerging contaminants in marine coastal waters, with concentrations reported in the low ng/L range. Although at relatively lower levels with respect to other pharmaceuticals, antidepressants – fluoxetine (FLX) in particular - have attracted attention because of their striking effects exerted at low doses on marine invertebrates. In this study, the effects of four antidepressants including FLX, sertraline (SER), and citalopram, as members of the selective serotonin reuptake inhibitor (SSRI) class, and venlafaxine (VEN) as a member of the serotonin and norepinephrine reuptake inhibitor (SNRI) class, were evaluated in the mussel Mytilus galloprovincialis. In addition, the effects of two main metabolites of FLX and VEN, i.e., norfluoxetine (NFL) and O-desmethylvenlafaxine (ODV) respectively, were compared to those of the parent compounds. Eight concentrations of each drug (0.5–500 ng/L range) were tested on the early life stage endpoints of gamete fertilization and larval development at 48 h post fertilization (hpf). Egg fertilization was reduced by all compounds, except for VEN. Larval development at 48 hpf was affected by all SSRIs, but not by SNRIs. The above effects were significant but never exceeded 20 % of control values. Adult mussels were exposed in vivo for 7 days to environmental concentrations of the drugs (0.5, 5, and 10 ng/L) and a battery of eight biomarkers was assessed. Antidepressants primarily targeted lysosomal functions, decreasing haemocyte lysosome membrane stability (up to 70 % reduction) and increasing of the lysosome/cytosol ratio (up to 220 %), neutral lipid (up to 230 %), and lipofuscin (up to 440 %) accumulation in digestive gland. Only SER and NFL significantly affected catalase and glutathione-S-transferase activities in gills and digestive gland. NFL and ODV, were effective and sometimes more active than the parent compounds. All compounds impaired mussel health status, as indicated by the low to high stress levels assigned using the Mussel Expert System.

Revitalizing Inert Materials: Grafting Self‐Oscillating, Stimuli‐Responsive Organometallic Polymers for Pulsating Systems

AbstractA major challenge in materials science is dynamically adjusting material properties using sensors and control systems. This contribution develops a new approach using a self‐oscillating copolymer to autonomously change material surface properties in response to environmental changes. A redox‐sensitive terpolymer of N‐isopropylacrylamide (NIPAM), dimethylacrylamide (DMAc), and an iron‐based comonomer ([(phen)2(phen‐5‐yl‐acrylamide)FeII](PF6)2) is synthesized via Reversible Addition‐Fragmentation Chain Transfer (RAFT) polymerization, catalyzing an oscillating redox reaction (Belousov‐Zhabotinsky, BZ). The terpolymer oscillates from soluble to insoluble around 35 °C based on the iron's oxidation state. A catechol unit is incorporated to enhance versatility, enabling grafting onto different surfaces. Optimal BZ reagent concentrations are explored for maximum oscillation amplitude and frequency. By selecting a working temperature between redox transition points, the copolymer's oscillation from coil to globular conformation is observed due to redox oscillations. The self‐oscillating copolymer is grafted onto an ultrafiltration membrane, where conformational changes cause variations in pore size, leading to rapid negative flux peaks that disrupt the flux and reduce membrane fouling during protein filtration. This study highlights self‐oscillating polymers' ability to impart dynamic properties to inert materials, paving the way for smart materials with self‐regulating properties to adapt to changing conditions.

16S rRNA gene sequencing reveals the effect of fluoxetine on gut microbiota in chronic unpredictable stress-induced depressive-like rats

ObjectivesGut microbiota is relevant to the pathogenesis of mental disorders including depression. This study aimed to investigate the influence of fluoxetine (FLX) on the gut microbiota in rats with Chronic Unpredictable Mild Stresses (CUMS)-induced depression.ResultsWe confirmed that the 28-day CUMS-induced depression rat model. Chronic FLX administration weakly improved depressive-like behaviors in rats. Illumina 16S rRNA gene sequencing on rat feces showed CUMS increased the relative abundance of Firmicutes (60.31% vs. 48.09% in Control, p < 0.05) and Lactobacillus genus (21.06% vs. 6.82% in control, p < 0.05); FLX and CUMS increased Bacilli class (20.00% ~ 24.08% vs. 10.31% in control, p < 0.05).ConclusionCollectively, our study showed that both CUMS and FLX changed the compositions of gut microbiota in rats. FLX and CUMS distinctly regulated the gut microbiota in depressed rats.

Combined Chronic Oral Methylphenidate and Fluoxetine Treatment During Adolescence: Effects on Behavior.

Attention Deficit Hyperactivity Disorder (ADHD) can be comorbid with depression, often leading to the prescription of both methylphenidate (MP) and selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (FLX). Moreover, these drugs are often misused as cognitive enhancers. This study examined the effects of chronic oral co-administration of MP and FLX on depressive- and anxiety-like behaviors. Adolescent rats received daily either water (control), MP, FLX, or the combination of MP plus FLX in their drinking water over the course of 4 weeks. Data analysis shows a decrease in food consumption and body weight for rats exposed to FLX or the combination of MP and FLX. Sucrose consumption was significantly greater in FLX or MP+FLX groups compared to controls. FLX-treated rats showed no effect in the elevated plus maze (EPM; open arm time) and forced swim test (FST; latency to immobility). However, rats treated with the combination (MP+FLX) showed significant anxiolytic-like and anti-depressive-like behaviors (as measured by EPM and FST), as well as significant increases in overall activity (distance traveled in open field test). Finally, the combined MP+FLX treatment induced a decrease in anxiety and depressive- like behaviors significantly greater than the response from either of these drugs alone. These behavioral results characterize the long-term effects of these drugs (orally administered) that are widely co-administered and co-misused and provide important insight into the potential neurobiological and neurochemical effects. Future research will determine the potential risks of the long-term use of MP and FLX together.

Demonstration and Comparison of On-Chip High-Frequency Test Methods for RSFQ Circuits

On-chip high-frequency test for Rapid Single Flux Quantum (RSFQ) circuits without external high-frequency equipment is very attractive and promising. The test method based on Shift Register (SR) is widely used for long time. Recently, we have proposed two test methods based on Pseudo Random Binary Sequence (PRBS) generator. In this paper, a Full Adder (FA) is taken as an example of circuit under test and the design methodology of the above approaches is presented. For FA with the traditional and two proposed approaches, the high-frequency test circuits are fabricated and tested. We demonstrate the successful measurement of the three circuits with the maximum operating frequency of the full adder at 23.3 GHz, 26.2 GHz and 27.4 GHz respectively. Based on the experimental results, the clock frequency measurement in the proposed two PRBS based test systems is more accurate and time-saving, which is advantageous for high-frequency RSFQ circuits measurement.

Wire Length-Matching Aware Placement Method for Rapid Single Flux Quantum Logic Circuits

This paper proposes a fast automatic gate placement method for gate-level-pipelined Rapid Single Flux Quantum (RSFQ) circuits that are designed to have a high throughput. In such circuits, the gates in a pipeline stage are placed in a column and wires are routed in the area between adjacent columns. In wire routing, wire length-matching is performed. The proposed method performs gate placement for a given netlist to minimize the sum of the maximum distance between connected gates in each pair of adjacent columns. It leads to short wire extensions in wire length matching for increasing the operation frequency and small circuit area. The proposed method consists of a recursive procedure including two placements, selecting a pivot column, and determining the gate placement in the pivot column. The netlist is divided into two netlists with the pivot column. The recursive procedure performs gate placements for the two divided netlist. It is repeated until the location of every gate is determined. We implemented a placement tool by the proposed method and performed the gate placement for three circuits including several hundreds of gates. The proposed placement was 14 to 40 times faster than a placement based on simulated annealing where the sum of the maximum distance between connected gates is approximately the same.

Striking a Good Balance Between Area and Throughput of RSFQ Circuits Containing Feedback Loops

Electronic design automation solutions are being developed to support the synthesis and physical design optimization of Rapid Single Flux Quantum (RSFQ) logic circuits with hundreds of thousands of logic cells. The clocked feature of synchronous RSFQ cells results in gate-level pipelined designs, requiring a large number of path-balancing D-flipflops (DFFs). In addition, one also faces the challenge of maintaining high throughput for RSFQ circuits containing feedback loops. To enforce the coincidence of the input and feedback patterns, one can apply a new input pattern every <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$L$</tex-math></inline-formula> cycles, where <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$L$</tex-math></inline-formula> is the length of the feedback loop. Consequently, the throughput of circuits with feedback loops is only <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$1/L$</tex-math></inline-formula> of the clock frequency. In this paper, we present two methods to improve the performance and area of RSFQ circuits, especially targeting circuits with feedback loops: (i) An area-oriented optimization method that removes the path-balancing DFFs by capturing and repeating input patterns. (ii) A throughput-oriented optimization method that enables an RSFQ circuit to receive and correctly process an input pattern every clock cycle. For a large circuit such as S526 in the ISCAS89 benchmark circuits, the circuit can initially receive an input pattern only every 9 cycles. As a result of applying our area-oriented optimization, the circuit admits 33% fewer logic cells while receiving input patterns every 11 cycles. Alternatively, our throughput-oriented optimization yields a circuit that can receive new input patterns on every cycle with nearly the same cell count.

60-GHz Single Flux Quantum Pulse Transfer Circuit for Serial Biasing

Serial Biasing (SB) is a technique to reduce the total DC bias current of Rapid Single Flux Quantum (RSFQ) circuits by partitioning a design into several islands with isolated grounds and sequential biasing. In this paper we focus on the design of a driver-receiver pair (DRP) to transfer pulses between islands that are galvanically isolated for pulse streams. We discuss both DRP itself and the structure for its testing, that comprises several DRPs connected in series, on-chip pseudo random binary sequence (PRBS) generator for circuit stimulation, and HF output interface. We use the layout of DRPs’ chain as an example to illustrate the advantage of the grapevine (GV) approach, introduced earlier, to manage the bias current flowing into and out of an island. The GV current management technique is analyzed by both electromagnetic simulations and measurement, compared, and contrasted with the so-called ‘straightforward’ (SF) approach. The maximum operational frequency for SF test structure was 10 GHz with zero margins for the SB current. Measurements of the GV structure at 10 GHz demonstrated BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−12</sup> with ±5.8% margins for SB current. We observed the correct operation of the 5-island DRP chain up to 60 GHz using the grapevine approach for SB current management. All chips were fabricated at MIT Lincoln Laboratory using SFQ5ee fab node.

Power Optimization of 50 GHz ERSFQ Circuits

The Energy-efficient Rapid Single Flux Quantum (ERSFQ) logic family offers zero-static power dissipation. Any ERSFQ circuit requires a feeding Josephson transmission line (FJTL), a relatively large active transmission line, which serves as an accurate voltage source. For proper operation, the FJTL needs to be continuously pumped at a frequency that is equal to or higher than the highest clock frequency of the ERSFQ circuit. We selected an on-chip pseudo-random binary sequence (PRBS) generator as the example circuit since it naturally facilitates quantitative measurements of operating bias margins in terms of bit error rate (BER). Using external and internal flux pump sources, we performed extensive experimental studies on BER for ERSFQ PRBS generators operating at clock frequencies up to 50 GHz. We paid special attention to the over-pumping regime, where the FJTL pump frequency is higher than the PRBS clock frequency and confirmed its superiority in improving BER. At 35.56 GHz clock frequency, a group of 4 PRBS generators and 4 individual FJTLs with the bias current ratio (BCR) equal to 1, had a BER lower than 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> and bias margins of ±25% for internal and external flux pump sources over-pumping at 6.25% above clock frequency. The maximal operational clock frequency of a single ERSFQ PRBS generator with intrinsic pump source (+6.25% over-pumping) and BER <10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> was 49.53 GHz. We also focused on optimization of the FJTL's size to reduce the power consumption and the area occupied by the FJTL itself. All chips were fabricated at MIT-Lincoln Laboratory using the SFQ5ee fab node. Future steps required for better understanding of ERSFQ operation are discussed.

Superconducting-Oscillatory Neural Network With Pixel Error Detection for Image Recognition

Brain-inspired oscillatory neural networks (ONNs) utilize coupled oscillators to emulate biological neuronal dynamics. ONNs are naturally suitable for image/pattern recognition. Many hardware implementations of ONNs have been explored recently by using analog or digital CMOS systems, which can be limited by Moore's law. In this work, we used one of the advanced superconducting technologies for coupled oscillator networks to further improve the energy efficiency and processing speed. Inductively coupled ring oscillators using rapid single flux quantum (RSFQ) technology were designed and simulated. These Josephson junction (JJ) based oscillators can operate as fast as tens of GHz but only consume a energy of several aJ per operation. Excluding cryo-cooling factors, the estimated power consumption of our RSFQ oscillator is hundreds of nW at a frequency of 12.5 GHz, which is multiple times smaller than a typical CMOS ring oscillator. Furthermore, a system for pattern recognition with error detection was designed based on these oscillators. Synchronization dynamics in a pair of coupled oscillators were used to identify whether a test pixel matches a reference pixel. A network comprised of 16 pairs of oscillators were wired together, along with synchronization detectors and a fluxon integrator to demonstrate pattern recognition function. This work was performed using standard JJ models and demonstrated through WRspice and JoSIM software simulations. The circuits and systems proposed in this work aim to provide insights into the use of superconducting technology for implementing ONNs and may serve as basic building blocks for the design of more complex oscillatory computational networks in image processing and beyond. Single oscillator modeling and systematic network function exploration will be performed in future work.

Adopting a Standard Track Routing Architecture for Next-Generation Hybrid AC/DC-Biased Logic Circuits

The adiabatic quantum-flux-parametron (AQFP) and rapid single flux quantum (RSFQ) logic families both provide distinct advantages for data processing using superconductor electronics. The development of next-generation AQFP-RSFQ hybrid logic circuits provides the opportunity to combine the benefits of both of these logic families. Adopting a standard track routing architecture for both AQFP and RSFQ layouts provides a unified framework for physical layout synthesis. We demonstrate a standard track routing architecture developed under the ColdFlux project and its implementation within AQFP. An additional advantage of the standard track routing architecture is that it provides a systematic way to overcome metal density requirements for modern-day fabrication processes. It also provides a methodical approach towards strategic moat placement for protection against unwanted flux trapping. Implementations of passive transmission line (PTL) connections and their physical placement for hybrid AQFP-RSFQ circuits are discussed. Several AQFP layouts for the ColdFlux project are redesigned to adopt the standard track routing architecture. Experimental simulation of moat performance is also presented.

$\upalpha$-Soma: Single Flux Quantum Threshold Cell for Spiking Neural Network Implementations

The main challenge for the hardware implementation of spiking neural networks is the design of a reliable neuron. Soma, which is the nucleus of the neuron, is a key part of such a design. More precisely, the soma design must accurately capture the excitatory/inhibitory interactions, intrinsic charge dynamics, refractory period, spike encoding, neuronal action potential, and output spike firing processes in order to mimic the corresponding biological processes. This work presents the design of an artificial soma cell with excitatory and inhibitory inputs, called <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\alpha$</tex-math></inline-formula> -Soma. The key idea is to design and employ a new interconnect cell, named <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\alpha$</tex-math></inline-formula> -cell, and integrate this cell within the proposed soma cell design. The design implementation utilizes the Rapid Single Flux Quantum (RSFQ) logic circuit technology. We demonstrate the correct functionality, high performance, and energy efficiency of the proposed <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\alpha$</tex-math></inline-formula> -Soma cell with detailed circuit simulations under different spiking conditions.

A comparative study of efficacy of ropivacaine (0.75%) with adjuvants – dexmedetomidine and fentanyl in supraclavicular brachial plexus block

Background: Brachial plexus block is preferred to general anesthesia (GA) as it reduces many complications of GA, provides good intra and postoperative analgesia, adequate muscle relaxation. Addition of adjuvants along with LA is used to prolong block with improved quality of anesthesia and decrease dose of LA. This study was done to see the efficacy of Ropivacaine with dexmedetomidine and fentanyl in terms of duration of action and pain relief. Aims and Objectives: Dexmedetomidine and Fentanyl along with Ropivacaine in patients undergoing upper limb surgeries, the onset and duration of sensory and motor blockade as well as post op analgesia is compared. Materials and Methods: Prospective Randomized Comparative study with three groups randomly divided received total volume of 30 mL of drug in peripheral nerve stimulator guided supraclavicular blocks in patients undergoing upper limb surgeries. Group Dexmedetomidine received 28 cc of 0.75% Ropivacaine and Dexmedetomidine (1 mcg/kg), Group Fentanyl patients received 28 cc of 0.75% Ropivacaine and fentanyl (1 mcg/kg), whereas, group plain Ropivacaine patients received 28 cc of 0.75% Ropivacaine and 2 mL of normal saline. Haemodynamics, sensory and motor block (MB) were evaluated by VAS and modified Bromage scale. Results: The onset of sensory block and MB in the dexmedetomidine group, fentanyl group, and ropivacaine groups was 3.57±0.50 min and 4.47±0.51 min, 5.50±0.51 min and 7.53±0.51 min, and 8.07±0.79 min and 10.07±0.79 min respectively which were statistically significant. The duration of MB in the dexmedetomidine group, fentanyl group, and ropivacaine group were 6.57±0.50 h, 4.47±0.51 h, and 2.50±0.51 h respectively which was statistically significant (P=0.0000). The duration at which first postoperative analgesia was required in the dexmedetomidine group, fentanyl group, and ropivacaine group were 8.57±0.50 h, 6.57±0.50 h, and 5.30±0.47 h respectively. Conclusion: Dexmedetomidine is better as an adjuvant to Ropivacaine for brachial plexus block in terms of onset and duration.

Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring

Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.

Theoretical insights of the pharmaceutical compound fluoxetine in water: Role in direct photolysis and indirect photolysis by free radicals

The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness, which may pose a major threat to the aquatic environment. In this study, photodegradation (direct and indirect photolysis) of two different dissociation states of fluoxetine (FLU) was investigated in water, mainly including the determination of photolytic transition states and products, and the mechanisms of indirect photodegradation with ·OH, CO3*− and NO3*. The main direct photolysis pathways are defluorination and C–C bond cleavage. In addition, the indirect photodegradation of FLU in water is mainly through the reactions with ·OH and NO3*, and the photodegradation reaction with CO3*− is relatively difficult to occur in the water environment. Our results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.

Low power single flux quantum qubit control circuit without high-frequency input

The use of high-frequency input signals from room-temperature microwave sources makes it difficult to scale up the number of quantum bits in universal quantum computers. To address this issue, superconducting single flux quantum (SFQ) integrated circuits are being explored as suitable candidates for qubit manipulation in universal quantum computers. This paper deals with a scalable SFQ qubit control circuit (SQCC) structure that requires only low-frequency input. The circuit mainly consists of a pulse generator and a counter, that output the SFQ pulse train with adjustable frequency and a controllable number of pulses, which is applicable to control single-qubit Clifford operations. The design of low-voltage rapid single flux quantum (LV-RSFQ) and energy-efficient rapid single flux quantum (ERSFQ) for the SQCC achieves low power consumption and provides a basis for scaling up SQCC to control more qubits. The proposed circuits are fabricated under the SIMIT-Nb03 process and successfully pass test verification. The achieved test results reveal that the adjustable output frequency ranges of the SQCC based on the LV-RSFQ and ERSFQ designs in order are [2.40, 8.11] GHz and [4.81, 5.14] GHz. In the operating frequency range, the circuit is able to generate the correct number of SFQ pulses under control. The controllable number range is from 1 to 128. When the circuits operate at 5 GHz, the total power consumptions of the above circuits in order are 23.88 μW and 6.2 μW. All input signals are low-frequency signals, which frees the control of large-scale qubits from limitations caused by high-frequency inputs produced by room-temperature microwave sources.

Stereoselective study of fluoxetine and norfluoxetine across the blood-brain barrier mediated by organic cation transporter 1/3 in rats using an enantioselective UPLC-MS/MS method.

Fluoxetine (FLT) is a widely used antidepressant in clinical practice, which can be metabolized into active norfluoxetine (NFLT) in vivo. The stereoselectivity of FLT and NFLT enantiomers across the blood-brain barrier (BBB) is still to be clarified. In this study, accurate and reliable UPLC-MS/MS enantioselective analysis was established in rat plasma and brain. The characteristics of FLT and NFLT enantiomers across the BBB were studied by chemical knockout of rat transporters. We found that the dominant enantiomers of FLT and NFLT were S-FLT and R-NFLT, respectively, both in plasma and in brain. The FLT and NFLT enantiomers showed significant stereoselectivity across the BBB, and S-FLT and S-NFLT were the dominant configurations across the BBB. Chemical knockout of organic cation transporter 1 (OCT1) and OCT3 can affect the ratio of plasma FLT and NFLT enantiomers into the brain, suggesting that OCT1/3 is stereoselective for FLT and NFLT transport across the BBB.