Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice.

Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Müller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson's disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs.

The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding the extent to which, and how, host genetics contributes to this variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans2. Here we study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and the abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3 kb deletion in the gene encoding N-acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.

Asymmetric connections with starburst amacrine cells underlie the upward motion selectivity of J-type retinal ganglion cells.

Motion is an important aspect of visual information. The directions of visual motion are encoded in the retina by direction-selective ganglion cells (DSGCs). ON-OFF DSGCs and ON DSGCs co-stratify with starburst amacrine cells (SACs) in the inner plexiform layer and depend on SACs for their direction selectivity. J-type retinal ganglion cells (J-RGCs), a type of OFF DSGCs in the mouse retina, on the other hand, do not co-stratify with SACs, and how direction selectivity in J-RGCs emerges has not been understood. Here, we report that both the excitatory and inhibitory synaptic inputs to J-RGCs are direction-selective (DS), with the inhibitory inputs playing a more important role for direction selectivity. The DS inhibitory inputs come from SACs, and the functional connections between J-RGCs and SACs are spatially asymmetric. Thus, J-RGCs and SACs form functionally important synaptic contacts even though their dendritic arbors show little overlap. These findings underscore the need to look beyond the neurons' stratification patterns in retinal circuit studies. Our results also highlight the critical role of SACs for retinal direction selectivity.

A synaptic filtering mechanism in visual threat identification in mouse.

Predator detection is key to animal's survival. Superior colliculus (SC) orchestrates the animal's innate defensive responses to visually detected threats, but how threat information is transmitted from the retina to SC is unknown. We discovered that narrow-field neurons in SC were key in this pathway. Using in vivo calcium imaging and optogenetics-assisted interrogation of circuit and synaptic connections, we found that the visual responses of narrow-field neurons were correlated with the animal's defensive behaviors toward visual stimuli. Activation of these neurons triggered defensive behaviors, and ablation of them impaired the animals' defensive responses to looming stimuli. They receive monosynaptic inputs from looming-sensitive OFF-transient alpha retinal ganglion cells, and the synaptic transmission has a unique band-pass feature that helps to shape their stimulus selectivity. Our results describe a cell-type specific retinotectal connection for visual threat detection, and a coding mechanism based on synaptic filtering.

Gene identification and semisynthesis of the anti-inflammatory oleanane-type triterpenoid wilforlide A.

Wilforlide A is one of the main active constituents produced in trace amounts in Tripterygium wilfordii Hook F, which has excellent anti-inflammatory and immune suppressive effects. Despite the seeming structural simplicity of the compound, the biosynthetic pathway of wilforlide A remains unknown. Gene-specific expression analysis and genome mining were used to identify the gene candidates, and their functions were studied in vitro and in vivo. A modularized two-step (M2S) technique and CRISPR-Cas9 methods were used to construct engineering yeast. Here, we identified a cytochrome P450, TwCYP82AS1, that catalyses C-22 hydroxylation during wilforlide A biosynthesis. We also found that TwCYP712K1 to K3 can further oxidize the C-29 carboxylation of oleanane-type triterpenes in addition to friedelane-type triterpenes. Reconstitution of the biosynthetic pathway in engineered yeast increased the precursor supply, and combining TwCYP82AS1 and TwCYP712Ks produced abrusgenic acid, which was briefly acidified to achieve the semisynthesis of wilforlide A. Our work presents an alternative metabolic engineering approach for obtaining wilforlide A without relying on extraction from plants.

Imprinted gene detection effectively improves the diagnostic accuracy for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. METHODS: A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. RESULTS: A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. CONCLUSION: The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.

Characterization of the Cytochrome P450 CYP716C52 in Celastrol Biosynthesis and Its Applications in Engineered Saccharomyces cerevisiae.

Celastrol is a bioactive pentacyclic triterpenoid with promising therapeutic effects that is mainly distributed in Celastraceae plants. Although some enzymes involved in the celastrol biosynthesis pathway have been reported, many biosynthetic steps remain unknown. Herein, transcriptomics and metabolic profiles of multiple species in Celastraceae were integrated to screen for cytochrome P450s (CYPs) that are closely related to celastrol biosynthesis. The CYP716 enzyme, TwCYP716C52, was found to be able to oxidize the C-2 position of polpunonic acid, a precursor of celastrol, to form the wilforic acid C. RNAi-mediated repression of TwCYP716C52 in Tripterygium wilfordii suspension cells further confirmed its involvement in celastrol biosynthesis. The C-2 catalytic mechanisms of TwCYP716C52 were further explored by using molecular docking and site-directed mutagenesis experiments. Moreover, a modular optimization strategy was used to construct an engineered yeast to produce wilforic acid C at a titer of 5.8 mg·L-1. This study elucidates the celastrol biosynthetic pathway and provides important functional genes and sufficient precursors for further enzyme discovery.

Enhancing biocathode denitrification performance with nano-Fe3O4 under polarity period reversal.

The presence of excessive concentrations of nitrate poses a threat to both the environment and human health, and the bioelectrochemical systems (BESs) are attractive green technologies for nitrate removal. However, the denitrification efficiency in the BESs is still limited by slow biofilm formation and nitrate removal. In this work, we demonstrate the efficacy of novel combination of magnetite nanoparticles (nano-Fe3O4) with the anode-cathode polarity period reversal (PPR-Fe3O4) for improving the performance of BESs. After only two-week cultivation, the highest cathodic current density (7.71 ± 1.01 A m-2) and NO3--N removal rate (8.19 ± 0.97 g m-2 d-1) reported to date were obtained in the PPR-Fe3O4 process (i.e., polarity period reversal with nano-Fe3O4 added) at applied working voltage of -0.2 and -0.5 V (vs Ag/AgCl) under bioanodic and biocathodic conditions, respectively. Compared with the polarity reversal once only process, the PPR process (i.e., polarity period reversal in the absence of nano-Fe3O4) enhanced bioelectroactivity through increasing biofilm biomass and altering microbial community structure. Nano-Fe3O4 could enhance extracellular electron transfer as a result of promoting the formation of extracellular polymers containing Fe3O4 and reducing charge transfer resistance of bioelectrodes. This work develops a novel biocathode denitrification strategy to achieve efficient nitrate removal after rapid cultivation.

A Fuzzy-PI Clock Servo with Window Filter for Compensating Queue-Induced Delay Asymmetry in IEEE 1588 Networks.

Clock synchronization is one of the popular research topics in Distributed Measurement and Control Systems (DMCSs). In most industrial fields, such as Smart Grid and Flight Test, the highest requirement for synchronization accuracy is 1 µs. IEEE 1588 Precision Time Protocol-2008 (PTPv2) can theoretically achieve sub-microsecond accuracy, but it relies on the assumption that the forward and backward delays of PTP packets are symmetrical. In practice, PTP packets will experience random queue delays in switches, making the above assumption challenging to satisfy and causing poor synchronization accuracy. Although using switches supporting the Transparent Clock (TC) can improve synchronization accuracy, these dedicated switches are generally expensive. This paper designs a PTP clock servo for compensating Queue-Induced Delay Asymmetry (QIDA), which can be implemented based on ordinary switches. Its main algorithm comprises a minimum window filter with drift compensation and a fuzzy proportional-integral (PI) controller. We construct a low-cost hardware platform (the cost of each node is within USD 10) to test the performance of the clock servo. In a 100 Mbps network with background (BG) traffic of less than 70 Mbps, the maximum absolute time error (max |TE|) does not exceed 0.35 µs, and the convergence time is about half a minute. The accuracy is improved hundreds of times compared with other existing clock servos.

Diagnostic accuracy of qualitative and quantitative magnetic resonance imaging-guided contrast-enhanced ultrasound (MRI-guided CEUS) for the detection of prostate cancer: a prospective and multicenter study.

PURPOSE: To evaluate the diagnostic value of MRI-guided contrast-enhanced ultrasound (CEUS) for prostate cancer (PCa) diagnosis, and characteristics of PCa in qualitative and quantitative CEUS. MATERIAL AND METHODS: This prospective and multicenter study included 250 patients (133 in the training cohort, 57 in the validation cohort and 60 in the test cohort) who underwent MRI, MRI-guided CEUS and prostate biopsy between March 2021 and February 2023. MRI interpretation, qualitative and quantitative CEUS analysis were conducted. Multitree extreme gradient boosting (XGBoost) machine learning-based models were applied to select the eight most important quantitative parameters. Univariate and multivariate logistic regression models were constructed to select independent predictors of PCa. Diagnostic value was determined for MRI, qualitative and quantitative CEUS using the area under receiver operating characteristic curve (AUC). RESULTS: The performance of quantitative CEUS was superior to that of the qualitative CEUS and MRI in predicting PCa. The AUC was 0.779 (95%CI 0.70-0.849), 0.756 (95%CI 0.638-0.874) and 0.759 (95%CI 0.638-0.879) of qualitative CEUS, and 0.885 (95%CI 0.831-0.940), 0.802 (95%CI 0.684-0.919) and 0.824 (95%CI 0.713-0.936) of quantitative CEUS in training, validation and test cohort, respectively. Compared with quantitative CEUS, MRI achieved less well performance for AUC 0.811 (95%CI 0.741-0.882, p = 0.099), 0.748 (95%CI 0.628-0.868, p = 0.539) and 0.737 (95%CI 0.602-0.873, p = 0.029), respectively. Moreover, the highest specificity of 80.6% was obtained by quantitative CEUS. CONCLUSION: We developed a reliable method of MRI-guided CEUS that demonstrated enhanced performance compared to MRI. The qualitative and quantitative CEUS characteristics will contribute to improved diagnosis of PCa.

Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Highly Promiscuous Flavonoid Di-O-glycosyltransferases from Carthamus tinctorius L.

Safflower (Carthamus tinctorius L.) has been recognized for its medicinal value, but there have been limited studies on the glycosyltransferases involved in the biosynthesis of flavonoid glycosides from safflower. In this research, we identified two highly efficient flavonoid O-glycosyltransferases, CtOGT1 and CtOGT2, from safflower performing local BLAST alignment. By constructing a prokaryotic expression vector, we conducted in vitro enzymatic reactions and discovered that these enzymes were capable of catalyzing two-step O-glycosylation using substrates such as kaempferol, quercetin, and eriodictyol. Moreover, they exhibited efficient catalytic activity towards various compounds, including flavones (apigenin, scutellarein), dihydrochalcone (phloretin), isoflavones (genistein, daidzein), flavanones (naringenin, glycyrrhizin), and flavanonols (dihydrokaempferol), leading to the formation of O-glycosides. The broad substrate specificity of these enzymes is noteworthy. This study provides valuable insights into the biosynthetic pathways of flavonoid glycosides in safflower. The discovery of CtOGT1 and CtOGT2 enhances our understanding of the enzymatic processes involved in synthesizing flavonoid glycosides in safflower, contributing to the overall comprehension of secondary metabolite biosynthesis in this plant species.

Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast.

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A- and D-rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)-glaziovine, (S)-glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.

[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.

High-Performance Thermoelectric Fibers from Metal-Backboned Polymers for Body-Temperature Wearable Power Devices.

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 µW ⋅m-1 K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

Host factor Rab11a is critical for efficient assembly of influenza A virus genomic segments.

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.

Cytochrome P450s in plant terpenoid biosynthesis: discovery, characterization and metabolic engineering.

As the largest family of natural products, terpenoids play valuable roles in medicine, agriculture, cosmetics and food. However, the traditional methods that rely on direct extraction from the original plants not only produce low yields, but also result in waste of resources, and are not applicable at all to endangered species. Modern heterologous biosynthesis is considered a promising, efficient, and sustainable production method, but it relies on the premise of a complete analysis of the biosynthetic pathway of terpenoids, especially the functionalization processes involving downstream cytochrome P450s. In this review, we systematically introduce the biotech approaches used to discover and characterize plant terpenoid-related P450s in recent years. In addition, we propose corresponding metabolic engineering approaches to increase the effective expression of P450 and improve the yield of terpenoids, and also elaborate on metabolic engineering strategies and examples of heterologous biosynthesis of terpenoids in Saccharomyces cerevisiae and plant hosts. Finally, we provide perspectives for the biotech approaches to be developed for future research on terpenoid-related P450.

Effectiveness and Accuracy of MRI-Ultrasound Fusion Targeted Biopsy Based on PI-RADS v2.1 Category in Transition/Peripheral Zone of the Prostate.

BACKGROUND: MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear. PURPOSE: To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively. STUDY TYPE: Retrospective. SUBJECTS: A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled. FIELD STRENGTH/SEQUENCE: A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE). ASSESSMENT: Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively. STATISTICAL TESTS: McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant. RESULTS: Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3-5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant. DATA CONCLUSION: MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Early visual motion experience shapes the gap junction connections among direction selective ganglion cells.

Gap junction connections between neurons play critical roles in the development of the nervous system. However, studies on the sensory experience-driven plasticity during the critical period rarely examine the involvement of gap junction connections. ON-OFF direction selective ganglion cells (ooDSGCs) in the mouse retina that prefer upward motion are connected by gap junctions throughout development. Here, we show that after exposing the mice to a visual environment dominated by upward motion from eye-opening to puberty, ooDSGCs that respond preferentially to upward motion show enhanced spike synchronization, while downward motion training has the opposite effect. The effect is long-term, persisting at least three months after the training. Correlated activity during training is tightly linked to this effect: Cells trained by stimuli that promote higher levels of activity correlation show stronger gap junction connection after the training, while stimuli that produce very low activity correlation leave the cells with much weaker gap junction connections afterwards. Direct investigation of the gap junction connections among upward motion-preferring ooDSGCs show that both the percentage of electrically coupled ooDSGCs and the strength of the coupling are affected by visual motion training. Our results demonstrate that in the retina, one of the peripheral sensory systems, gap junction connections can be shaped by experience during development.

Sustainable and Reagentless Fenton Treatment of Complex Wastewater.

Conventional Fenton treatment is fundamentally impractical for large-scale applications, as the consumption of Fe(II), H2O2, and pH regulators and the accumulation of iron hydroxide sludge are very costly. This paper describes a new method for Fenton treatment of complex wastewater without additional dosing of Fe(II) and H2O2, without iron-sludge accumulation, and with less consumption of pH regulators, using a novel bioelectrode system. Our new system includes a novel three-chamber microbial electrolysis unit and Fenton reaction unit, where Fenton reagents are generated by biotic and abiotic cathodes, while the bioanode simultaneously degrades biodegradable organics from the wastewater. The system's self-alkalinity buffering also waives the need for pH regulators. Dissolved organic carbon and 22 specific recalcitrant organics were removed by 99% and between 78 and 100%, respectively. The bioelectrode system generated 13 ± 3 mg/L dissolved Fe(II) and 5 ± 0.4 mg/L H2O2 for the Fenton reaction unit. The closed iron cycle avoided iron loss and iron sludge accumulation during operation. The pH regulator dosage and operating costs were just 9.7 and 1.4%, respectively, of what is required by classic Fenton. The low operating cost and reduction in chemical usage make it an efficient, sustainable alternative to the conventional treatment processes currently used for complex wastewater.