Anion optimization for bifunctional surface passivation in perovskite solar cells.

Pseudo-halide (PH) anion engineering has emerged as a surface passivation strategy of interest for perovskite-based optoelectronics; but until now, PH anions have led to insufficient defect passivation and thus to undesired deep impurity states. The size of the chemical space of PH anions (>106 molecules) has so far limited attempts to explore the full family of candidate molecules. We created a machine learning workflow to speed up the discovery process using full-density functional theory calculations for training the model. The physics-informed machine learning model allowed us to pinpoint promising molecules with a head group that prevents lattice distortion and anti-site defect formation, and a tail group optimized for strong attachment to the surface. We identified 15 potential bifunctional PH anions with the ability to passivate both donors and acceptors, and through experimentation, discovered that sodium thioglycolate was the most effective passivant. This strategy resulted in a power-conversion efficiency of 24.56% with a high open-circuit voltage of 1.19 volts (24.04% National Renewable Energy Lab-certified quasi-steady-state) in inverted perovskite solar cells. Encapsulated devices maintained 96% of their initial power-conversion energy during 900 hours of one-sun operation at the maximum power point.

Doping Shortens the Metal/Metal Distance and Promotes OH Coverage in Non-Noble Acidic Oxygen Evolution Reaction Catalysts.

Acidic water electrolysis enables the production of hydrogen for use as a chemical and as a fuel. The acidic environment hinders water electrolysis on non-noble catalysts, a result of the sluggish kinetics associated with the adsorbate evolution mechanism, reliant as it is on four concerted proton-electron transfer steps. Enabling a faster mechanism with non-noble catalysts will help to further advance acidic water electrolysis. Here, we report evidence that doping Ba cations into a Co3O4 framework to form Co3-xBaxO4 promotes the oxide path mechanism and simultaneously improves activity in acidic electrolytes. Co3-xBaxO4 catalysts reported herein exhibit an overpotential of 278 mV at 10 mA/cm2 in 0.5 M H2SO4 electrolyte and are stable over 110 h of continuous water oxidation operation. We find that the incorporation of Ba cations shortens the Co-Co distance and promotes OH adsorption, findings we link to improved water oxidation in acidic electrolyte.

Ion Substitution Strategy of Manganese-Based Layered Oxide Cathodes for Advanced and Low-Cost Sodium Ion Batteries.

Sodium ion batteries (SIBs) have recently been promising in the large-scale electric energy storage system, due to the low cost, abundant sodium resources. Mn-based layered oxide cathode materials have been widely investigated, because of the high theoretical specific capacity, low cost, and abundant reserves. However, their development is limited by the problems of Jahn-Teller distortion, Na+ /vacancy ordering, complex phase transitions, and irreversible anionic redox during cycling. Ion substitution strategy is one simple and effective way to regulate the crystal structure and boost sodium-storage performances of Mn-based cathode materials. In this review, we summarize the progress and mechanism of ion-substituted Mn-based oxides, establish a composition-crystal structure-electrochemical performance relationship, and also offer perspectives for guiding the design of high-performance Mn-based oxides for SIBs.

Competitive Doping Chemistry for Nickel-Rich Layered Oxide Cathode Materials.

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than BIII . In the case of Al-preoccupation, the bulk diffusion of BIII is hindered. In this way, a B-rich surface and Al-rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.

mTOR may interact with PARP-1 to regulate visible light-induced parthanatos in photoreceptors.

BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

Intramuscular Injection of Adenoassociated Virus Encoding Human Neurotrophic Factor 3 and Exercise Intervention Contribute to Reduce Spasms after Spinal Cord Injury.

Limb spasms are phenomena of hyperreflexia that occur after spinal cord injury. Currently, the clinical treatment is less than ideal. Our goal is to develop a combination therapy based on individualized medicine to reduce spasticity after spinal cord injury. In this study, rats received a severe contusive injury at the T9 segment of the spinal cord, followed by gene therapy with adenoassociated virus encoding human neurotrophic factor 3 (AAV-NT3) and a 2-week exercise program starting at 4 weeks after injury. We quantified the frequency of spasms during a swimming test at 4 and 6 weeks after injury and confirmed the results of the swimming test by measuring the H-reflex of the plantar muscle. We obtained weekly hind limb exercise scores to assess the effect of the interventions in hind limb motor function improvement. Then, we used immunofluorescence to observe the immunoreactivity of spinal motor neurons, synaptophysin, cholinergic interneurons, and GABAergic interneurons. We also measured the expression of KCC2 in the spinal cord by western blot. We found that AAV-NT3 gene therapy, exercise, and combination therapy all attenuated the frequency of spasms in the swimming test conducted at 6 weeks after spinal cord injury and increased rate-dependent depression of H-reflex. Combination therapy was significantly superior to AAV-NT3 alone in protecting motor neurons. Recovery of KCC2 expression was significantly greater in rats treated with combination therapy than in the exercise group. Combination therapy was also significantly superior to individual therapies in remodeling spinal cord neurons. Our study shows that the combination of AAV-NT3 gene therapy and exercise can alleviate muscle spasm after spinal cord injury by altering the excitability of spinal interneurons and motor neurons. However, combination therapy did not show a significant additive effect, which needs to be improved by adjusting the combined strategy.

Boosting Sodium Compensation Efficiency via a CNT/MnO2 Catalyst toward High-Performance Na-Ion Batteries.

The formation of a solid electrolyte interphase on carbon anodes causes irreversible loss of Na+ ions, significantly compromising the energy density of Na-ion full cells. Sodium compensation additives can effectively address the irreversible sodium loss but suffer from high decomposition voltage induced by low electrochemical activity. Herein, we propose a universal electrocatalytic sodium compensation strategy by introducing a carbon nanotube (CNT)/MnO2 catalyst to realize full utilization of sodium compensation additives at a much-reduced decomposition voltage. The well-organized CNT/MnO2 composite with high catalytic activity, good electronic conductivity, and abundant reaction sites enables sodium compensation additives to decompose at significantly reduced voltages (from 4.40 to 3.90 V vs Na+/Na for sodium oxalate, 3.88 V for sodium carbonate, and even 3.80 V for sodium citrate). As a result, sodium oxalate as the optimal additive achieves a specific capacity of 394 mAh g-1, almost reaching its theoretical capacity in the first charge, increasing the energy density of the Na-ion full cell from 111 to 158 Wh kg-1 with improved cycle stability and rate capability. This work offers a valuable approach to enhance sodium compensation efficiency, promising high-performance energy storage devices in the future.

Bismuth-doping boosting Na+ diffusion kinetics of layered oxide cathode with radially oriented {010} active lattice facet for sodium-ion batteries.

O3-type layered oxide cathodes (NaxTMO2) for sodium-ion batteries (SIBs) have attracted significant attention as one of the most promising potential candidates for practical energy storage applications. The poor Na+ diffusion kinetics is, however, one of the major obstacles to advancing large-scale practical application. Herein, we report bismuth-doped O3-NaNi0.5Mn0.5O2 (NMB) microspheres consisting of unique primary nanoplatelets with the radially oriented {010} active lattice facets. The NMB combines the advantages of the oriented and exposed electrochemical active planes for direct paths of Na+ diffusion, and the thick primary nanoplatelets for less surface parasitic reactions with the electrolyte. Consequently, the NMB cathode exhibits a long-term stability with an excellent capacity retention of 72.5% at 1C after 300 cycles and an enhanced rate capability at a 0.1C to 10C rate (1C = 240 mA g-1). Furthermore, the enhancement is elucidated by the small volume change, thin cathode-electrolyte-interphase (CEI) layer, and rapid Na+ diffusion kinetics. In particular, the radial orientation-based Bi-doping strategy is demonstrated to be effective at boosting electrochemical performance in other layered oxides (such as Bi-doped NaNi0.45Mn0.45Ti0.1O2 and NaNi1/3Fe1/3Mn1/3O2). The results provide a promising strategy of utilizing the advantages of the oriented active facets of primary platelets and secondary particles to develop high-rate layered oxide cathodes for SIBs.

Referred pain: characteristics, possible mechanisms, and clinical management.

Purpose of this review: Referred pain is a common but less understood symptom that originates from somatic tissues. A comprehensive recognition of referred pain is important for clinicians when dealing with it. The purpose of this study is to summarize the current understanding of referred pain, including its pathogenesis, characteristics, diagnosis, and treatment. Recent findings: Referred pain arises not only from pathologies primarily involving local tissue but also from lesions in distant structures. Central sensitization of convergent neurons and peripheral reflexes of dichotomizing afferent fibers are two theories proposed to explain the pathological mechanism of referred pain. Because syndromes related to referred pain of different origins overlap each other, it is challenging to define referred pain and identify its originating lesions. Although various approaches have been used in the diagnosis and treatment of referred pain, including conservative treatment, blockade, radiofrequency, and surgery, management of referred pain remains a clinical challenge. Summary: Unlike radicular pain and neuropathic pain, referred pain is a less studied area, despite being common in clinics. Referred pain can derive from various spinal structures, and blockage helps identify the primary pathology. Due to the heterogeneity of referred pain, treatment outcomes remain uncertain. Further studies are needed to improve our understanding of referred pain.

Cu/Ti co-doping boosting P2-type Fe/Mn-based layered oxide cathodes for high-performance sodium storage.

Environmentally friendly P2-type layered iron manganese oxides appear to be one of the most potential cathode materials for sodium-ion batteries (SIBs). However, their practical application is hindered by the unfavorable phase transitions, dissolution of transition metals, and poor air stability. One effective strategy by either single-cation doping or high-cost Li involved co-doping is used to alleviate the problems. Here, low-cost Cu/Ti co-doping is introduced to boost P2-Na0.7Cu0.2Fe0.2Mn0.5Ti0.1O2 as an air and electrochemical stable cathode material for SIBs. The resulting electrode delivers an initial capacity of 130 mAh g-1 at 0.1C within 2.0-4.2 V, a reversible discharge capacity of 61.0 mAh g-1 at a high rate of 5C and a capacity retention ratio exceeding 71.1% after 300 cycles. In particular, the co-doped crystal structure is well-maintained after 1 month of exposure to air, and even 3 days of soaking in water. Furthermore, the enhancement is elucidated by the effectively mitigated P2-Z and the completely suppressed P2-P'2 phase transitions, the decreased volume variation proved by in-situ X-ray diffraction (XRD), as well as the lowered transition-metal dissolution evidenced by inductively coupled plasma optical emission spectrometer (ICP-OES) and X-ray photoelectron spectroscopy (XPS). The low-lost Cu/Ti doping strategy could thus be effective for designing and preparing environmentally friendly and high-performance cathode materials for SIBs.

Fair Survival Time Prediction via Mutual Information Minimization.

Survival analysis is a general framework for predicting the time until a specific event occurs, often in the presence of censoring. Although this framework is widely used in practice, few studies to date have considered fairness for time-to-event outcomes, despite recent significant advances in the algorithmic fairness literature more broadly. In this paper, we propose a framework to achieve demographic parity in survival analysis models by minimizing the mutual information between predicted time-to-event and sensitive attributes. We show that our approach effectively minimizes mutual information to encourage statistical independence of time-to-event predictions and sensitive attributes. Furthermore, we propose four types of disparity assessment metrics based on common survival analysis metrics. Through experiments on multiple benchmark datasets, we demonstrate that by minimizing the dependence between the prediction and the sensitive attributes, our method can systematically improve the fairness of survival predictions and is robust to censoring.

O3-Type Na0.95Ni0.40Fe0.15Mn0.3Ti0.15O2 Cathode Materials with Enhanced Storage Stability for High-Energy Na-Ion Batteries.

O3-type layered oxides with high initial sodium content are promising cathode candidates for Na-ion batteries. However, affected by the undesired transition metal slab sliding and reaction with H2O/CO2, their further application is typically hindered by unsatisfactory cycling stability upon charging to high voltage and poor storage stability under humid air. Herein, we demonstrate a Fe/Ti cosubstitution strategy to simultaneously enhance the electrochemical performance and storage stability of pristine O3-NaNi0.5Mn0.5O2 cathode material, via employing high redox potential and inactive stabilized dopants. The resultant Fe/Ti cosubstituted Na0.95Ni0.40Fe0.15Mn0.3Ti0.15O2 undergoes highly reversible O3-P3-OP2 phase transitions with a small cell volume change of 2.8%, instead of complex O3-O'3-P3-P'3-P3'-O1 phase transitions in NaNi0.5Mn0.5O2. Consequently, the cathode displays a high specific capacity of 161.6 mAh g-1 with an average working voltage of 3.28 V and 81.8% capacity retention after 200 cycles at 5C. Furthermore, the cathode material remains very stable after exposure to air for 7 days and even after soaking in water for 1 h, owing to the prohibition of sodium losing by elevating redox potential and contracting sodium layer spacing. This work proposes an effective method to enhance the electrochemical performance and storage stability of O3-type layered oxide cathodes and promises advancing Na-ion batteries toward large-scale industrialization.

Metal-Organic Frameworks Functionalized Separators for Robust Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are one of the promising energy storage systems, which consist of electrode materials, electrolyte, and separator. The first two have been significantly received ample development, while the prominent role of the separators in manipulating the stability of the electrode has not attracted sufficient attention. In this work, a separator (UiO-66-GF) modified by Zr-based metal organic framework for robust AZIBs is proposed. UiO-66-GF effectively enhances the transport ability of charge carriers and demonstrates preferential orientation of (002) crystal plane, which is favorable for corrosion resistance and dendrite-free zinc deposition. Consequently, Zn|UiO-66-GF-2.2|Zn cells exhibit highly reversible plating/stripping behavior with long cycle life over 1650 h at 2.0 mA cm-2, and Zn|UiO-66-GF-2.2|MnO2 cells show excellent long-term stability with capacity retention of 85% after 1000 cycles. The reasonable design and application of multifunctional metal organic frameworks modified separators provide useful guidance for constructing durable AZIBs.

Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood-brain barrier in rodents and primates.

The development of gene therapies for the treatment of diseases of the central nervous system has been hindered by the limited availability of adeno-associated viruses (AAVs) that efficiently traverse the blood-brain barrier (BBB). Here, we report the rational design of AAV9 variants displaying cell-penetrating peptides on the viral capsid and the identification of two variants, AAV.CPP.16 and AAV.CPP.21, with improved transduction efficiencies of cells of the central nervous system on systemic delivery (6- to 249-fold across 4 mouse strains and 5-fold in cynomolgus macaques, with respect to the AAV9 parent vector). We also show that the neurotropism of AAV.CPP.16 is retained in young and adult macaques, that this variant displays enhanced transcytosis at the BBB as well as increased efficiency of cellular transduction relative to AAV9, and that it can be used to deliver antitumour payloads in a mouse model of glioblastoma. AAV capsids that can efficiently penetrate the BBB will facilitate the clinical translation of gene therapies aimed at the central nervous system.

Application of fibrin-based hydrogels for nerve protection and regeneration after spinal cord injury.

Traffic accidents, falls, and many other events may cause traumatic spinal cord injuries (SCIs), resulting in nerve cells and extracellular matrix loss in the spinal cord, along with blood loss, inflammation, oxidative stress (OS), and others. The continuous development of neural tissue engineering has attracted increasing attention on the application of fibrin hydrogels in repairing SCIs. Except for excellent biocompatibility, flexibility, and plasticity, fibrin, a component of extracellular matrix (ECM), can be equipped with cells, ECM protein, and various growth factors to promote damage repair. This review will focus on the advantages and disadvantages of fibrin hydrogels from different sources, as well as the various modifications for internal topographical guidance during the polymerization. From the perspective of further improvement of cell function before and after the delivery of stem cell, cytokine, and drug, this review will also evaluate the application of fibrin hydrogels as a carrier to the therapy of nerve repair and regeneration, to mirror the recent development tendency and challenge.

Preparation, characterization and evaluation of a new film based on chitosan, arginine and gold nanoparticle derivatives for wound-healing efficacy.

It is well-known that the combination of polymers and nanoparticles (NPs) provides optimised wound dressing and accelerates wound healing. The knowledge about the structure and properties of these materials is of critical importance in biological processes related to wound healing. In this study, we prepared a chitosan (CS) film modified with arginine (Arg) and gold NPs (AuNPs) and investigated its effectiveness as a dressing material for wound healing. Fourier-transform infrared spectroscopy (FTIR) confirmed that Arg was successfully grafted on CS. The resultant CS-Arg/AuNP film was then characterised by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The modification of Arg and AuNPs improved the hydrophilicity, mechanical strength and antibacterial properties of the film, which in turn provided an enhanced ideal environment for cell adhesion and proliferation. Cell Counting Kit-8 (CCK-8) was used to demonstrate the survival rate. Furthermore, the proteins involved in wound healing were evaluated qualitatively and quantitatively by immunofluorescence and western blotting, respectively. The skin defect models used for the in vivo studies revealed that the CS-Arg/AuNP dressing accelerated wound closure, re-epithelialization and collagen deposition. Our cumulative findings support the feasibility of using the proposed film as a promising candidate for tissue engineering of the skin in the near future.

Advances in the application of gold nanoparticles in bone tissue engineering.

The materials used in bone tissue engineering (BTE) have been advancing with each passing day. With the continuous development of nanomedicine, gold nanoparticles (GNPs), which are easy to be synthesized and functionalized, have attracted increasing attention. Recent years have witnessed this amazing material, i.e., GNPs characterized with large surface area to volume ratio, biocompatibility, medical imaging property, hypotoxicity, translocation into the cells, high reactivity, and other properties, perform distinct functions in BTE. However, the low stability of GNPs in the biotic environment makes them in the requirements of modification or recombination before being used. After being combined with the advantages of other materials, the structures of GNPs have exhibited great potential in stem cells, scaffolds, delivery systems, medical imaging, and other aspects. This review will focus on the advances in the application of GNPs after modification or recombination with other materials to BTE.

The Advances of Ceria Nanoparticles for Biomedical Applications in Orthopaedics.

The ongoing biomedical nanotechnology has intrigued increasingly intense interests in cerium oxide nanoparticles, ceria nanoparticles or nano-ceria (CeO2-NPs). Their remarkable vacancy-oxygen defect (VO) facilitates the redox process and catalytic activity. The verification has illustrated that CeO2-NPs, a nanozyme based on inorganic nanoparticles, can achieve the anti-inflammatory effect, cancer resistance, and angiogenesis. Also, they can well complement other materials in tissue engineering (TE). Pertinent to the properties of CeO2-NPs and the pragmatic biosynthesis methods, this review will emphasize the recent application of CeO2-NPs to orthopedic biomedicine, in particular, the bone tissue engineering (BTE). The presentation, assessment, and outlook of the orthopedic potential and shortcomings of CeO2-NPs in this review expect to provide reference values for the future research and development of therapeutic agents based on CeO2-NPs.

Local delivery of FTY720 and NSCs on electrospun PLGA scaffolds improves functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a common issue in the clinic that causes severe motor and sensory dysfunction below the lesion level. FTY720, also known as fingolimod, has recently been reported to exert a positive effect on the recovery from a spinal cord injury. Through local delivery to the lesion site, FTY720 effectively integrates with biomaterials, and the systemic adverse effects are alleviated. However, the effects of the proper mass ratio of FTY720 in biomaterials on neural stem cell (NSC) proliferation and differentiation, as well as functional recovery after SCI, have not been thoroughly investigated. In our study, we fabricated electrospun poly (lactide-co-glycolide) (PLGA)/FTY720 scaffolds at different mass ratios (0.1%, 1%, and 10%) and characterized these scaffolds. The effects of electrospun PLGA/FTY720 scaffolds on NSC proliferation and differentiation were measured. Then, a rat model of spinal transection was established to investigate the effects of PLGA/FTY720 scaffolds loaded with NSCs. Notably, 1% PLGA/FTY720 scaffolds exerted the best effects on the proliferation and differentiation of NSCs and 10% PLGA/FTY720 was cytotoxic to NSCs. Based on the Basso, Beattie, and Bresnahan (BBB) score, HE staining and immunofluorescence staining, the PLGA/FTY720 scaffold loaded with NSCs effectively promoted the recovery of spinal cord function. Thus, FTY720 properly integrated with electrospun PLGA scaffolds, and electrospun PLGA/FTY720 scaffolds loaded with NSCs may have potential applications for SCI as a nerve implant.

Metabolic Engineering of Four GATA Factors to Reduce Urea and Ethyl Carbamate Formation in a Model Rice Wine System.

Urea is the most important precursor of ethyl carbamate (EC), a harmful carcinogenic product, in fermented wines. In this study, the effects of four GATA transcriptional factors (Gln3p, Gat1p, Dal80p ,and Gzf3p) on extracellular urea and EC formation and transcriptional changes in urea degradation related genes ( DUR1,2 and DUR3) were examined. Compared to the WT strain, the Δ gzf3 mutant showed 18.7% urea reduction and exhibited synergistic effects with overexpressed Gln3p1-653 and Gat1p1-375 on extracellular urea reduction. Moreover, Δ gzf3+Gln3p1-653 and Δ gzf3+Gat1p1-375 showed significant 38.7% and 43.7% decreases in urea concentration and 41.7% and 48.5% decreases in EC concentration, respectively, in a model rice wine system. These results provide a promising way to reduce urea and EC formation during wine fermentation and raise some cues for the regulations of the four GATA transcriptional factors on the expression of individual nitrogen catabolite repression sensitive genes and their related metabolism pathway.