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BACKGROUND: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). METHODS: Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. RESULTS: Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. CONCLUSIONS: Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.

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In this study, the effect of modulating fulvic acid (FA) concentrations (0, 25 and 50 mg/L) on nitrogen removal in a bioelectrochemical hydrogen autotrophic denitrification system (BHDS) was investigated. Results showed that FA increased the nitrate (NO3--N) removal rate of the BHDSs from 37.8 to 46.2 and 45.2 mg N/(L·d) with a current intensity of 40 mA. The metagenomic analysis revealed that R2 (25 mg/L) was predominantly populated by autotrophic denitrifying microorganisms, which enhanced denitrification performance by facilitating electron transfer. Conversely, R3 (50 mg/L) exhibited an increase in genes related to the heterotrophic process, which improved the denitrification performance through the collaborative action of both autotrophic and heterotrophic denitrification pathways. Besides, the study also identified a potential for nitrogen removal in Serpentinimonas, which have been rarely studied. The interesting set of findings provide valuable reference for optimizing BHDS for nitrogen removal and promoting specific denitrifying genera within the system.

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Fullerene-based derivatives are frequently used as electron transport materials (ETMs) and interface buffers for perovskite solar cells (PSCs) due to their excellent properties, including high electron affinity and mobility, low recombination energy, tunable energy levels, and solution processability. However, significant challenges arise because fullerene derivatives tend to aggregate and dimerize, which reduces exciton dissociation and charge transport capacity. Additionally, their chemical compatibility with perovskite absorbers facilitates halide diffusion and degradation of PSCs. This overlap causes delamination and dissolution during device fabrication, hindering the performance enhancement of fullerene-based PSCs. To address these issues, researchers have developed cross-linkable fullerene materials. These materials have been shown to not only significantly improve the power conversion efficiency (PCE) of PSCs but also effectively enhance the device stability. In this review, we summarized recent research progress on cross-linkable fullerene derivatives as ETMs for PSCs. We systematically analyze the impact of these cross-linked ETMs on device performance and long-term stability, focusing on their molecular structures and working mechanisms. Finally, we discuss the future challenges that need to be overcome to advance the application of cross-linkable fullerene materials in PSCs.

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The brain is an energy demanding organ, constituting about 20 % of the body's resting metabolic rate. An efficient energy metabolism is critical to neuronal functions. Glucose serves as the primary essential energy source for the adult brain and plays a critical role in supporting neural growth and development. Endocrine disrupting chemicals (EDCs) such as phthalates has been shown to have a negative impact on neurological functions. The impact of diisononyl phthalate (DiNP) on neural energy transduction using cellular energy metabolizing enzymes as indicators was examined. Over the course of 14 days, eighteen (18) albino rats divided into three groups (1,2 and 3) of six albino rats were given Tween-80/saline, 20 and 200 mg/kg body weight respectively. In the brain, we assessed histological changes as well as activities of selected enzymes of energy metabolism such as the glycolytic pathway, citric acid cycle and mitochondrial electron transport-linked complexes. Activities of the glycolytic and TCA cycle enzymes assayed were significantly decreased except citrate synthase activity with no statistically significant change following the administration of DiNP. Also, respiratory chain complexes (Complex I-IV) activities were significantly reduced when compared to control. DiNP exposure altered the histological integrity of various brain sections. These include degenerated Purkinje neurons, distortion of the granular layer and Purkinje cell layer. Data from this study indicated impaired brain energy metabolism via down-regulation of enzymes of cellular respiration of the glycolytic and oxidative phosphorylation pathways and altered brain histoarchitecture orchestrated by DiNP exposure.

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In order to enhance the overall efficiency of colloidal quantum dots solar cells, it is crucial to suppress the recombination of charge carriers and minimize energy loss at the interfaces between the transparent electrode, electron transport layer (ETL), and colloidal quantum dots (CQDs) light-absorbing material. In the current study, ZnO/SrTiO3 (STO), ZnO/WO3 (TO), and ZnO/Zn2SnO4 (ZTO) bilayers are introduced as an ETL using a spin-coating technique. The ZTO interlayer exhibits a smoother surface with a root-mean-square (RMS) value of ≈ 3.28 nm compared to STO and TO interlayers, which enables it to cover the surface of the ITO/ZnO substrate entirely and helps to prevent direct contact between the CQDs absorber layer and the ITO/ZnO substrate, thereby effectively preventing efficient charge recombination at the interfaces of the ETL/CQDs. Furthermore, the ZTO interlayer possesses superior electron mobility, a higher visible light transmission, and a suitable energy band structure compared to STO and TO. These characteristics are advantageous for extracting charge carriers and facilitating electron transport. The PbS CQDs solar cell based on the ITO/ZnO/ZTO/PbS-FABr/PbS-EDT/NiO/Au device configuration exhibits the highest efficiency of 15.28%, which is significantly superior than the ITO/ZnO/PbS-FABr/PbS-EDT/NiO/Au solar cell device (PCE = 14.38%). This study is anticipated to offer a practical approach to develop ultrathin and compact ETL for highly efficient CQDSCs.

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Traditional leaf gas exchange experiments have focused on net CO2 exchange (Anet). Here, using California poplar (Populus trichocarpa), we coupled measurements of net oxygen production (NOP), isoprene emissions and δ18O in O2 to traditional CO2/H2O gas exchange with chlorophyll fluorescence, and measured light, CO2 and temperature response curves. This allowed us to obtain a comprehensive picture of the photosynthetic redox budget including electron transport rate (ETR) and estimates of the mean assimilatory quotient (AQ = Anet/NOP). We found that Anet and NOP were linearly correlated across environmental gradients with similar observed AQ values during light (1.25 ± 0.05) and CO2 responses (1.23 ± 0.07). In contrast, AQ was suppressed during leaf temperature responses in the light (0.87 ± 0.28), potentially due to the acceleration of alternative ETR sinks like lipid synthesis. Anet and NOP had an optimum temperature (Topt) of 31°C, while ETR and δ18O in O2 (35°C) and isoprene emissions (39°C) had distinctly higher Topt. The results confirm a tight connection between water oxidation and ETR and support a view of light-dependent lipid synthesis primarily driven by photosynthetic ATP/NADPH not consumed by the Calvin-Benson cycle, as an important thermotolerance mechanism linked with high rates of (photo)respiration and CO2/O2 recycling.

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Breast cancer cells exhibit metabolic heterogeneity based on tumour aggressiveness. Glycolysis and mitochondrial respiration are two major metabolic pathways for ATP production. The oxygen flux, oxygen tension, proton leakage, protonmotive force, inner mitochondrial membrane potential, ECAR and electrochemical proton gradient maintain metabolic homeostasis, ATP production, ROS generation, heat dissipation, and carbon flow and are referred to as "sub-domains" of mitochondrial bioenergetics. Tumour aggressiveness is influenced by these mechanisms, especially when breast cancer cells undergo metastasis. These physiological parameters for healthy mitochondria are as crucial as energy demands for tumour growth and metastasis. The instant energy demands are already elucidated under Warburg effects, while these parameters may have dual functionality to maintain cellular bioenergetics and cellular health. The tumour cell might maintain these mitochondrial parameters for mitochondrial health or avoid apoptosis, while energy production could be a second priority. This review focuses explicitly on the crosstalk between metabolic domains and the utilisation of these parameters by breast cancer cells for their progression. Some major interventions are discussed based on mitochondrial bioenergetics that need further investigation. This review highlights the pathophysiological significance of mitochondrial bioenergetics and the regulation of its sub-domains by breast tumour cells for uncontrolled proliferation.

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The photocatalytic activity and inherent brittleness of ZnO, which is commonly used as an electron transport layer (ETL) in inverted organic solar cells (OSCs), have impeded advancements in device stability and the development of fully stretchable OSCs. In this study, we have developed an intrinsically stretchable ETL for inverted OSCs through a side-chain cross-linking strategy. Specifically, cross-linking between bromine atoms on the side chains of a quinoidal compound and the amino groups in polyethylenimine resulted in a film, designated QBr-PEI-50, with high electrical conductivity (0.049 S/m) and excellent stretchability (crack-onset strain >45%). When used as the ETL in inverted OSCs, QBr-PEI-50 was markedly superior to ZnO in terms of device performance and stability, yielding a power conversion efficiency (PCE) of 18.27% and a T80 lifetime exceeding 10000 h. Moreover, incorporation of QBr-PEI-50 in fully stretchable inverted OSCs yielded a PCE of 14.01%, and 80% of the initial PCE was maintained after 21% strain, showcasing its potential for wearable electronics.

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In the realm of photovoltaic research, 2D transition metal carbides (MXenes) have gained significant interest due to their exceptional photoelectric capabilities. However, the instability of MXenes due to oxidation has a direct impact on their practical applications. In this work, the oxidation process of Nb2CTx MXene in aqueous systems is methodically simulated at the atomic level and nanosecond timescales, which elucidates the structural variations influenced by the synergistic effects of water and dissolved oxygen, predicting a transition from metal to semiconductor with 44% C atoms replaced by O atoms in Nb2CTx. Moreover, Nb2CTx with varying oxidation degrees is utilized as electron transport layers (ETLs) in perovskite solar cells (PSCs). Favorable energy level alignments with superior electron transfer capability are achieved by controlled oxidation. By further exploring the composites of Nb2CTx to its derivatives, the strong interaction of the nano-composites is demonstrated to be more effective for electron transport, thus the corresponding PSC achieves a better performance with long-term stability compared with the widely used ETLs like SnO2. This work unravels the oxidation dynamics of Nb2CTx and provides a promising approach to designing ETL by exploiting MXenes to their derivatives for photovoltaic technologies.

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Electron transport in complex fluids, biology, and soft matter is a valuable characteristic in processes ranging from redox reactions to electrochemical energy storage. These processes often employ conductor-insulator composites in which electron transport properties are fundamentally linked to the microstructure and dynamics of the conductive phase. While microstructure and dynamics are well recognized as key determinants of the electrical properties, a unified description of their effect has yet to be determined, especially under flowing conditions. In this work, the conductivity and shear viscosity are measured for conductive colloidal suspensions to build a unified description by exploiting both recent quantification of the effect of flow-induced dynamics on electron transport and well-established relationships between electrical properties, microstructure, and flow. These model suspensions consist of conductive carbon black (CB) particles dispersed in fluids of varying viscosities and dielectric constants. In a stable, well-characterized shear rate regime where all suspensions undergo self-similar agglomerate breakup, competing relationships between conductivity and shear rate were observed. To account for the role of variable agglomerate size, equivalent microstructural states were identified using a dimensionless fluid Mason number, [Formula: see text], which allowed for isolation of the role of dynamics on the flow-induced electron transport rate. At equivalent microstructural states, shear-enhanced particle-particle collisions are found to dominate the electron transport rate. This work rationalizes seemingly contradictory experimental observations in literature concerning the shear-dependent electrical properties of CB suspensions and can be extended to other flowing composite systems.

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We present a nonlinear spectroelectrochemical technique to investigate photosynthetic protein complexes. The PEC2DES setup combines photoelectrochemical detection (PEC) that selectively probes the protein photogenerated charges output with two-dimensional electronic spectroscopy (2DES) excitation that spreads the nonlinear optical response of the system in an excitation-detection map. PEC allows us to distinguish the contribution of charge separation (CS) from other de-excitation pathways, whereas 2DES allows us to disentangle congested spectral bands and evaluate the exciton dynamics (decays and coherences) of the photosystem complex. We have developed in operando phase-modulated 2DES by measuring the photoelectrochemical reaction rate in a biohybrid electrode functionalized with a plant photosystem complex I-light harvesting complex I (PSI-LHCI) layer. Optimizing the photoelectrochemical current signal yields reliable linear spectra unequivocally associated with PSI-LHCI. The 2DES signal is validated by nonlinear features like the characteristic vibrational coherence at 750 cm-1. However, no energy transfer dynamics is observed within the 450 fs experimental window. These intriguing results are discussed in the context of incoherent mixing resulting in reduced nonlinear contrast for multichromophoric complexes, such as the 160 chlorophyll PSI. The presented PEC2DES method identifies generated charges unlike purely optical 2DES and opens the way to probe the CS channel in multichromophoric complexes.

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SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.

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Pacific hagfish (Eptatretus stoutii) are an ancient agnathan vertebrate known to be anoxia tolerant. To study their metabolic organization and the role of the mitochondria in anoxia tolerance we developed a novel protocol to measure mitochondrial function in permeabilized cardiomyocytes and how this is affected by one hour of anoxia followed by reoxygenation. When measured at 10 °C the mitochondria had a respiration rate of 2.1 ± 0.1pmol/s/mg WW during OXPHOS with saturating concentrations of glutamate, malate, and succinate. This is comparatively low compared to other ectothermic species. The functional characteristics of the mitochondria were quantified with mitochondrial control ratios. These demonstrated that proton leak contributed to just under 50% of the oxygen flux, with the remainder going towards ATP phosphorylation. Finally, when the preparations were exposed to an anoxia-reoxygenation protocol there was no difference in respiration compared to that of a heart sample from the same animal maintained under normoxia for the same time. When Complex I alone or Complex I and II were stimulated following one hour of anoxia there was no decline in oxygen flux observed. However, if Complex II was activated alone there was a significant decline in respiration. This decrease was however also observed in the mitochondria maintained in normoxia for one hour. In conclusion, Pacific hagfish cardiac mitochondria demonstrated a low rate of oxygen consumption, a loosely coupled electron transfer system, and a resistance to one hour of anoxia.

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Photosynthetic microorganisms, which rely on light-driven electron transfer, store solar energy in self-energy carriers and convert it into bioenergy. Although these microorganisms can operate light-induced charge separation with nearly 100% quantum efficiency, their practical applications are inherently limited by the photosynthetic energy conversion efficiency. Artificial semiconductors can induce an electronic response to photoexcitation, providing additional excited electrons for natural photosynthesis to improve solar conversion efficiency. However, challenges remain in importing exogenous electrons across cell membranes. In this work, we have developed an engineered gold nanocluster/organic semiconductor heterostructure (AuNC@OFTF) to couple the intracellular electron transport chain of living cyanobacteria. AuNC@OFTF exhibits a prolonged excited state lifetime and effective charge separation. The internalized AuNC@OFTF permits its photogenerated electrons to participate in the downstream of photosystem II and construct an oriented electronic highway, which enables a five-fold increase in photocurrent in living cyanobacteria. Moreover, the binding events of AuNC@OFTF established an abiotic-biotic electronic interface at the thylakoid membrane to enhance electron flux and finally furnished nicotinamide adenine dinucleotide phosphate. Thus, AuNC@OFTF can be exploited to spatiotemporally manipulate and enhance the solar conversion of living cyanobacteria in cells, providing an extended nanotechnology for re-engineering photosynthetic pathways.

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Mitochondria play a key role in aging. Here, we measured integrated mitochondrial functions in experimentally evolved lines of the seed beetle Acanthoscelides obtectus that were selected for early (E) or late (L) reproduction for nearly four decades. The two lines have markedly different lifespans (8 days and 13 days in the E and L lines, respectively). The contribution of the NADH pathway to maximal flux was lower in the L compared to the E beetles at young stages, associated to increased control by complex I. In contrast, the contribution of the Succinate pathway was higher in the L than in the E line, while the Proline pathway showed no differences between the lines. Our data suggest that selection of age at reproduction leads to a modulation of complex I activity in mitochondria and that mitochondria are a functional link between evolutionary and mechanistic theories of aging.

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BACKGROUND: Nitrogen (N) is a crucial element for increasing photosynthesis and crop yields. The study aims to evaluate the photosynthetic regulation and yield formation mechanisms of different nodulating peanut varieties with N fertilizer application. METHOD: The present work explored the effect of N fertilizer application rates (N0, N45, N105, and N165) on the photosynthetic characteristics, chlorophyll fluorescence characteristics, dry matter, N accumulation, and yield of four peanut varieties. RESULTS: The results showed that N application increased the photosynthetic capacity, dry matter, N accumulation, and yield of peanuts. The measurement of chlorophyll a fluorescence revealed that the K-phase, J-phase, and I-phase from the OJIP curve decreased under N105 treatment compared with N0, and WOI, ET0/CSM, RE0/CSM, ET0/RC, RE0/RC, φPo, φEo, φRo, and Ψ0 increased, whereas VJ, VI, WK, ABS/RC, TR0/RC, DI0/RC, and φDo decreased. Meanwhile, the photosystem activity and electron transfer efficiency of nodulating peanut varieties decreased with an increase in N (N165). However, the photosynthetic capacity and yield of the non-nodulating peanut variety, which highly depended on N fertilizer, increased with an increase in N. CONCLUSION: Optimized N application (N105) increased the activity of the photosystem II (PSII) reaction center, improved the electron and energy transfer performance in the photosynthetic electron transport chain, and reduced the energy dissipation of leaves in nodulating peanut varieties, which is conducive to improving the yield. Nevertheless, high N (N165) had a positive effect on the photosystem and yield of non-nodulating peanut. The results provide highly valuable guidance for optimizing peanut N management and cultivation measures.

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Planar perovskite solar cells (PSCs), as a promising photovoltaic technology, have been extensively studied, with strong expectations for commercialization. Improving the power conversion efficiency (PCE) of PSCs is necessary to accelerate their practical application, in which the electron transport layer (ETL) plays a key part. Herein, a single-anchored ligand of phenylphosphonic acid (PPA) is utilized to regulate the chemical bath deposition of a TiO2 ETL, further improving the PCE of planar PSCs. The PPA possesses a steric benzene ring and a phosphoric acid group, which can inhibit the particle aggregation of the TiO2 film through steric hindrance, leading to optimized interface (ETL/perovskite) contact. In addition, the incorporated PPA can induce the upshift of the Fermi-level of the TiO2 film, which is beneficial for interfacial electron transport. As a consequence, the PSCs with PPA-TiO2 achieve a PCE of 24.83%, which is higher than that (24.21%) of PSCs with TiO2. In addition, the unencapsulated PSCs with PPA-TiO2 also exhibit enhanced stability when stored in ambient conditions.

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The rapid rise of antibiotic resistance calls for the discovery of new antibiotics with distinct antibacterial mechanisms. New target mining is indispensable for developing antibiotics. Plant-microbial antibiotics are appealing to underexplored sources due to a dearth of comprehensive understanding of antibacterial activity and the excavation of new targets. Here, a series of phloroglucinol derivatives of plant-root-associated Pseudomonas fluorescens were synthesized for structure-activity relationship analysis. Notably, 2,4-diproylphloroglucinol (DPPG) displayed efficient bactericidal activity against a wide range of gram-positive bacteria. Importantly, mechanistic study exhibits that DPPG binds to type II NADH dehydrogenase (NDH-2), an essential enzyme catalyzing the transfer of electrons from NADH to quinones in the electron transport chain (ETC), blocking electron transfer in S. aureus. Last, we validated the efficacy of DPPG in vivo through animal infection models. Our findings not only provide a distinct antibiotic lead to treat multidrug resistant pathogens but also identify a promising antibacterial target.

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The fabrication of ordered nanoarray electrode (NAE) using UV imprinting and their application as electrochemical (EC) immunosensor is described in this study. Especially, the influence of the array density factors on the performance of NAE was characterized electrochemically and compared with flat-electrode. Low-density (hole: 200 nm, hole space = 600 nm), medium-density (hole: 200 nm, hole space = 400 nm), and high-density NAE (hole: 200 nm, hole space = 200 nm) which have the same active area were fabricated and their redox cycling was compared with empirical results. We observed that the high-density is the optimum NAE exhibiting the lowest charge transfer resistance and the highest redox cycling performance among all NAEs. Finally, to observe the effect of their EC performance as biosensor, an EC immunoassay was performed using Interleukine-6 (IL-6), and high-density NAE has lowest a low limit of detection (LOD) of 0.45 pg/mL compared with other NAEs (medium-density: 3.91 pg/mL, low-density: 5.87 pg/mL).

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The electron transport layer (ETL) plays a critical role in efficient and stable perovskite solar cells (PSCs). The current effective method for the large-scale preparation of metal oxide ETLs is mainly based on expensive sputtering processes. Here, a screen-assisted self-spreading method is proposed as a novel approach to prepare uniformly thin and conformal TiO2 films on a rough fluorine-doped tin oxide (FTO) substrate as an ETL in planar PSCs. The TiO2 ETL deposited by this method exhibited good coverage and homogeneity on the rough FTO substrate, thereby minimizing interfacial recombination. The photovoltaic performance of the PSCs fabricated by this method is superior to that of the cells fabricated by spin coating, especially in terms of the fill factor. The performance enhancement can be attributed to the complete coverage of the FTO substrate by the conformal TiO2 film, confirming the effectiveness and reliability of the proposed method for the preparation of the TiO2 ETL. The advantages of this method lie in its scalability to prepare oxide films with a large area, eliminating the requirement of complex equipment, such as spinners, sputters, or physical vapor deposition equipment.