Exogenous Supply Research Articles

Exogenous hydrogen supply improves in-situ biogas upgrading of sewage sludge: Performance and mechanisms

In-situ biogas upgrading is a promising approach for enhancing carbon dioxide capture and efficient resource use. Recent investigations have highlighted that exogenous hydrogen can be used to purify biogas. However, the effects of exogenous hydrogen supply on in-situ biogas upgrading remain poorly understood. This study investigated the effects of direct and indirect hydrogen supply on in-situ biogas upgrading and elucidated potential underlying mechanisms. Significant enhancements were observed in methane production efficiency and biogas upgrading using an exogenous hydrogen supply. Batch tests showed that adding 10 g/L coarse zero valent iron (cZVI) resulted in a high cumulative methane yield of 286.4 mL/g-volatile solids (VS) and methane content of 95.5%, representing a 2.2-fold and 1.5-fold increase, respectively, compared to results in the absence of cZVI. In semi-continuous tests, the use of hollow fibers to enhance hydrogen diffusion led to an increased methane production rate (52.0 mL/g-VS·d), while less hydrogen was more favorable for biogas purification (92.0% methane). Further analysis revealed that an exogenous hydrogen supply enhances cooperative interactions between hydrolysis microbes, acetogenesis microbes, and methanogens to promote methane production and biogas upgrading. These findings provide valuable insights into the impact of exogenous hydrogen supply on in-situ biogas upgrading during anaerobic digestion of sewage sludge, informing future development of strategies for enhancing methane production and biogas upgrading from waste sources.

A quantitative autonomous bioluminescence reporter system with a wide dynamic range for Plant Synthetic Biology.

Plant Synthetic Biology aims to enhance the capacities of plants by designing and integrating synthetic gene circuits (SGCs). Quantitative reporting solutions that can produce quick, rich datasets affordably are necessary for SGC optimization. In this paper, we present a new, low-cost, and high-throughput reporter system for the quantitative measurement of gene expression in plants based on autonomous bioluminescence. This method eliminates the need for an exogenous supply of luciferase substrate by exploiting the entire Neonothopanus nambi fungal bioluminescence cyclic pathway to build a self-sustained reporter. The HispS gene, the pathway's limiting step, was set up as the reporter's transcriptional entry point as part of the new system's design, which significantly improved the output's dynamic range and brought it on par with that of the gold standard FLuc/RLuc reporter. Additionally, transient ratiometric measurements in N. benthamiana were made possible by the addition of an enhanced GFP as a normalizer. The performance of new NeoLuc/eGFP system was extensively validated with SGCs previously described, including phytohormone and optogenetic sensors. Furthermore, we employed NeoLuc/eGFP in the optimization of challenging SGCs, including new configurations for an agrochemical (copper) switch, a new blue optogenetic sensor, and a dual copper/red-light switch for tight regulation of metabolic pathways.

Enhanced lead phytoextraction and soil health restoration through exogenous supply of organic ligands: Geochemical modeling”

Phytoremediation of lead (Pb) contaminated soil is a green technology to reduce Pb exposure and root exudates-derived organic acids play a vital role in this treatment process. In this study, Pb hyperaccumulator Pelargonium hortorum was chosen to investigate root-induced organic acid secretions and their subsequent role in Pb phytoextraction. In the first step, root exudation of P. hortorum was investigated in hydroponic experiments (0.2X Hoagland solution) under control and Pb stress conditions. Possible chemical interactions between Pb and the observed root exudates were then analyzed using Visual MINTEQ modeling. In the next step, the effects of the exogenous application of organic acids on Pb phytoextraction and soil enzymatic activities were studied in a pot experimental setup. Results indicated significant exudation of malic acid > citric acid > oxalic acid > tartaric acid in root exudates of P. hortorum under 50 mg L−1 Pb. Visual MINTEQ modeling results revealed that organic acids directly affect Pb dissolution in the nutrient solution by modulation of solution pH. Experimental results revealed that malic acid and citric acid significantly increased available Pb contents (7.2– and 6.7–folds) in the soil with 1500 mg kg−1 Pb contamination. Whereas, in shoot and root, the highest increase in Pb concentration was observed with citric acid (2.01–fold) and malic (3.75–fold) supplements, respectively. Overall, Pb uptake was notably higher when malic acid was applied (2.8–fold) compared to other organic acids, followed by citric acid (2.7–fold). In the case of soil enzymatic activities, oxalic acid significantly improved dehydrogenase, alkaline phosphatase, and microbial biomass by 1.6–, 1.4– and 1.3–folds, respectively. The organic acids were successful in reviving enzyme activity in Pb-contaminated soil, and might thus be used for long-term soil regeneration.

Can healthy diets be achieved worldwide in 2050 without farmland expansion?

This paper analyses to what extent it would be possible to ensure food availability to the world population by 2050 with two objectives: healthy diets and no farmland expansion. Assumptions were made to project exogenous demand and supply variables. Climate change impacts on crop yields, grazing use intensities and maximum cultivable areas were taken into account. Cropland and pastureland needs were then estimated for 21 regions using a global biomass balance model. Simulation results established for two sets of crop yield projections (‘moderate’ versus ‘high’ growth) show that several regions (India, Rest of Asia, Near- and Middle-East countries and North Africa, as well as West Africa in the case of ‘moderate’ yield growth) would be constrained by their maximum cultivable areas with no deforestation. Our scenarios would be technically infeasible because of additional pastureland needs notably in sub-Saharan Africa. As a consequence, we analyse to what extent additional levers could reduce pastureland needs in sub-Saharan Africa.

Do Lower Search Costs Benefit Intermediaries?

Intermediaries—such as Amazon, Alibaba Group, and Walmart—play critical roles in digital markets: This paper proposes a model for analyzing how search cost affects their market outcomes. Distinguished from existing search literature, we introduce network effects to the market by allowing buyers to have positive preferences for product variety. In addition, we relax the exogenous demand and supply assumptions in the conventional search literature to study how search affects participation on both sides of the market. Through the model, we focus on studying and comparing two important types of intermediary: the two-sided platform; and the one-sided retailer. We find that reducing search costs does not necessarily increase the profit of both intermediary types. Furthermore, its influences are highly varied—depending on both the type of intermediary and its buyers’ preferences for variety.

Monetary transmission and government investment in China

The quantity measure of money supply—the M2 growth, in particular—has been used as the intermediate target of monetary policy in China since 2000. We document three findings on the transmission of money supply shocks to firm investment and financing over the period from 1998 to 2016. First, positive money supply shocks have significant negative effects on firm investment and do not have consistent impacts on firm financing, contradicting the standard monetary transmission mechanism. Second, using short-term global capital flows as an exogenous money supply factor, we recover the standard positive effect of money supply shocks on firm investment and financing, suggesting that M2 growth contains confounding factors and it is inappropriate to use it directly as an intermediate target or indicator of monetary policy. Third, we show that removing the government investment-related component from M2 growth leads to a monetary supply measure that conforms to the standard monetary transmission mechanism. Overall, we argue that our refined measure of M2 growth can serve as a superior indicator for the intermediate target of monetary policy in China.

Nature and Causes of Economic Fluctuations: Evidence from the U.S. Based on a Nonlinear Autoregressive Integrated Process

Business cycles and economic growth have long been studied separately, hindering understanding of the nature and causes of economic fluctuations and growth. Here, we present an economic model that incorporates both deterministic trends and persistent fluctuations, derived from a general economic data generation process obtained using the dimensionless nonlinear autoregressive integrated (NLARI) process. To explore the nature and causes of economic fluctuations and growth, we develop a unified test to identify whether the economic data generation mechanism is stable fixed points, unit roots, cyclical oscillations, or chaos. Empirical studies show that as the economic resilience coefficient changes from strong to weak, the data-generating mechanism for U.S. economic indicators shifts from a stable fixed point (dynamic equilibrium) in the supply-side economy to an unstable unit root (divergence) in the demand-side economy involving income distribution. Therefore, the U.S. economy is in partial dynamic equilibrium of the supply-side economy. The low resilience of the demand-side economy allows for the accumulation of noise from exogenous shocks, leading to persistent fluctuations. We find that the economic deterministic trend is ([Formula: see text]/[Formula: see text])[Formula: see text], i.e., time [Formula: see text] multiplied by the ratio of the mean of exogenous supply, demand, and technological progress investment shocks to the economic resistance coefficient. A general dynamic equilibrium economy maximizes growth from investment by avoiding [Formula: see text] growth losses from permanently persistent fluctuations. Thus, ([Formula: see text]/[Formula: see text])[Formula: see text] is the maximum value obtained along the maximum profit growth at the von Neumann equilibrium price. The investment path that creates the maximum ratio [Formula: see text]/[Formula: see text] is the optimal growth path.

Impaired Lactate Release in Dorsal CA1 Astrocytes Contributed to Nociceptive Sensitization and Comorbid Memory Deficits in Rodents.

Memory deficits are a common comorbid disorder in patients suffering from neuropathic pain. The mechanisms underlying the comorbidities remain elusive. The hypothesis of this study was that impaired lactate release from dysfunctional astrocytes in dorsal hippocampal CA1 contributed to memory deficits. A spared nerve injury model was established to induce both pain and memory deficits in rats and mice of both sexes. von Frey tests, novel object recognition, and conditioned place preference tests were applied to evaluate the behaviors. Whole-cell recording, fiber photometry, Western blotting, and immunohistochemistry combined with intracranial injections were used to explore the underlying mechanisms. Animals with spared sciatic nerve injury that had displayed nociception sensitization or memory deficit comorbidities demonstrated a reduction in the intrinsic excitability of pyramidal neurons, accompanied by reduced Ca2+ activation in astrocytes (ΔF/F, sham: 6 ± 2%; comorbidity: 2 ± 0.4%) and a decrease in the expression of glial fibrillary acidic protein and lactate levels in the dorsal CA1. Exogenous lactate supply or increasing endogenous lactate release by chemogenetic activation of astrocytes alleviated this comorbidity by enhancing the cell excitability (129 ± 4 vs. 88 ± 10 for 3.5 mM lactate) and potentiating N-methyl-d-aspartate receptor-mediated excitatory postsynaptic potentials of pyramidal neurons. In contrast, inhibition of lactate synthesis, blocking lactate transporters, or chemogenetic inhibition of astrocytes resulted in comorbidity-like behaviors in naive animals. Notably, β2-adrenergic receptors in astrocytes but not neurons were downregulated in dorsal CA1 after spared nerve injury. Microinjection of a β2 receptor agonist into dorsal CA1 or activation of the noradrenergic projections onto the hippocampus from the locus coeruleus alleviated the comorbidity, possibly by increasing lactate release. Impaired lactate release from dysfunctional astrocytes, which could be rescued by activation of the locus coeruleus, led to nociception and memory deficits after peripheral nerve injury.

The arginine decarboxylase gene CsADC1, associated with the polyamine pathway, plays an important role in tea cold tolerance

Arginine decarboxylase (ADC) is an important enzyme responsible for polyamine (PA) synthesis in plants. In our study, 5 tea varieties were used to investigate the relationship between ADC and cold tolerance in field experiments. A strong and positive correlation was found between cold stress-regulated expression levels of CsADC1 and arginine (Arg) content (R2 > 0.75) in tea mesophyll cells and cold tolerance in 5 tea varieties. An exogenous supply of Arg significantly enhanced cold tolerance. To further clarify the location of CsADC1, the full-length cDNA of the CsADC1 gene was cloned and located in the cell nucleus. Moreover, cold stress significantly promoted the production of MDA in CsADC1-silenced leaves compared with WT plants, which exhibited poor cold tolerance. In contrast, under cold conditions, higher Fv/Fm and lower MDA were detected in CsADC1-overexpressing Arabidopsis than in the WT plants. Furthermore, CsADC1-silenced leaves inhibited the expression levels of the PA metabolism genes CsAIH, CsCPA, CsSPDS, CsSPMS1 and CsSPMS2 under cold stress; thus, significantly lower (p < 0.05) putrescine (Put), spermidine (Spd) and spermine (Spm) content was d etected in CsADC1-silenced tea leaves under cold stress. Taken together, our results indicated that CsADC1, as a positive regulator, played an important role in cold tolerance, which may be due to modulation of polyamine pathways in the cold stress response.

Triple functional magnesium ascorbyl phosphate encapsulated hydrogel: A cosmetic ingredient promotes bone repair via anti-oxidation, calcium uptake and blood vessel remodeling

Bone defect repair involves a synergistic repair process involving the reconstruction of the skeletal system and remodeling of the neurological and vascular systems. However, current strategy/systems are mainly single function/purpose for bone repair. In this study, we propose a strategy that utilizes a simple but multifunctional cosmetic ingredient magnesium ascorbyl phosphate (MAP), for effective in situ cranial defect repair. MAP is loaded into a gelatin methacrylate hydrogel to achieve sustained release and the scaffold supply only phosphorus-containing compounds to promote bone repair without an exogenous supply of Ca2+. Results show that MAP can reduce oxidative stress damage in bone marrow-derived mesenchymal stem cells (BMSCs) by scavenging reactive oxygen species and promoting Ca2+ uptake to accelerate the mineralization of BMSCs in vitro. In addition, the pro-angiogenic and ERK/AKT signaling pathway activation abilities of MAP accelerate the biological process of bone defect repair. Micro-CT result reveal a greater repair rate in the 8-week MAP group (32.74 ± 0.62%) than in the control group (7.08 ± 0.29%). This study suggests that inorganic-phosphorus-based small-molecule delivery and calcium-free strategies have considerable potential in bone defect repair.

Towards intensified preservation technology of anammox granular sludge: Insights into the role of energy support

Anammox is an advanced biotechnology for nitrogen removal and has been widely applied in wastewater treatment. Preservation of anammox granular sludge (AnGS) is an essential approach to support the sustainable development of anammox processes. In this study, the activity descent and its mechanism of AnGS during long-term cryopreservation were investigated. The results showed that the cryopreservation process of AnGS could be divided into plummeting stage, maintaining stage and descending stage in terms of activity index, namely three-stage activity descent. A significant positive correlation was observed between the ATP pool and the three-stage activity descent (by hzo-mRNA/hzo-gene ratio) of AnGS (R2 = 0.944). The ATP pool was found to be replenished by the sequential consumption of endogenous energy substances, leading to the stationary activity of AnGS. The consumption of essential cell components as an energy source was revealed to cause damage and even death of functional bacteria, and the energy stress could be mitigated by the regular exogenous substrate supply. Consequently, the energy support in terms of ATP could be a feasible way to innovate the preservation technology and promote the sustainable development of anammox processes.

Skin Penetration Ability of 12 Hyaluronic Acids with Different Molecular Weights After Topical Application

Objective: Hyaluronic acid (HA) is a fundamental component of the extracellular matrix, regulating numerous biological processes. In humans, almost half of the total HA concentrates in the skin, but its availability decreases with age. Therefore, topical exogenous supplies of HA can reduce the aging process of the skin and can represent a valid alternative to the costly and invasive treatments based on injectable HA-based fillers. However, for cosmetically effective topical preparations, it is crucial to determine the properties favouring percutaneous HA penetration, such as HA molecular weight (MW). Therefore, the ability of 12 HA molecules with different MWs to penetrate the skin using an in vitro model was examined. Materials and Methods: The Franz diffusion cell experimental system was used to estimate the penetration of the HA molecules across three epidermal tissues. The relationship between MW and penetration was inspected by applying a Pearson’s correlation test.

Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression

Replication of the mitochondrial genome and expression of the genes it encodes both depend on a sufficient supply of nucleotides to mitochondria. Accordingly, dysregulated nucleotide metabolism not only destabilises the mitochondrial genome, but also affects its transcription. Here, we report that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria with pyrimidine ribonucleotides that are necessary for the transcription of mitochondrial genes. Loss of NME6 function leads to the depletion of mitochondrial transcripts, as well as destabilisation of the electron transport chain and impaired oxidative phosphorylation. These deficiencies are rescued by an exogenous supply of pyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNA when the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results therefore reveal an important role for ribonucleotide salvage in mitochondrial gene expression.

B cell-derived IL-10 promotes the resolution of lipopolysaccharide-induced acute lung injury

Inflammation resolution is critical for acute lung injury (ALI) recovery. Interleukin (IL)-10 is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-10 during the ALI resolution process in a murine lipopolysaccharide (LPS)-induced ALI model. Blockade of IL-10 signaling aggravates LPS-induced lung injury, as manifested by elevated pro-inflammatory factors production and increased neutrophils recruitment to the lung. Thereafter, we used IL-10 GFP reporter mice to discern the source cell of IL-10 during ALI. We found that IL-10 is predominantly generated by B cells during the ALI recovery process. Furthermore, we used IL-10-specific loss in B-cell mice to elucidate the effect of B-cell-derived IL-10 on the ALI resolution process. IL-10-specific loss in B cells leads to increased pro-inflammatory cytokine expression, persistent leukocyte infiltration, and prolonged alveolar barrier damage. Mechanistically, B cell-derived IL-10 inhibits the activation and recruitment of macrophages and downregulates the production of chemokine KC that recruits neutrophils to the lung. Moreover, we found that IL-10 deletion in B cells leads to alterations in the cGMP–PKG signaling pathway. In addition, an exogenous supply of IL-10 promotes recovery from LPS-induced ALI, and IL-10-secreting B cells are present in sepsis-related ARDS. This study highlights that B cell-derived IL-10 is critical for the resolution of LPS-induced ALI and may serve as a potential therapeutic target.

The Levels of DAHP Synthase, the First Enzyme of the Shikimate Pathway, Are Related to Free Aromatic Amino Acids and Glutamine Content in Nicotiana plumbaginifolia Cell Cultures.

Aromatic amino acid homeostasis was investigated in cell suspension cultures of Nicotiana plumbaginifolia and was related to the activity of the first enzyme in aromatic biosynthesis, 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase. An inverse relationship was found between the intracellular content of free phenylalanine, tyrosine and tryptophan and enzyme specific activity levels, suggesting the occurrence of end-product control mechanisms. Two DAHP synthase isogenes are present in wild tobacco that showed a different expression pattern during the culture growth cycle. Intracellular levels of aromatic amino acids were increased or decreased by adding the culture medium with phenylalanine, tyrosine and tryptophan, or with sublethal doses of the shikimate pathway inhibitor glyphosate, respectively. As a consequence, enzyme levels varied in the opposite direction. The concomitant exogenous supply of glutamine further reduced enzyme activity in mid-log cells, suggesting induction by both aromatic amino acid depletion and nitrogen starvation.

Induction of silicon defences in wheat landraces is local, not systemic, and driven by mobilization of soluble silicon to damaged leaves.

In response to herbivory, many grasses, including crops such as wheat, accumulate significant levels of silicon (Si) as an antiherbivore defence. Damage-induced increases in Si can be localized in damaged leaves or be more systemic, but the mechanisms leading to these differences in Si distribution remain untested. Ten genetically diverse wheat landraces (Triticum aestivum) were used to assess genotypic variation in Si induction in response to mechanical damage and how this was affected by exogenous Si supply. Total and soluble Si levels were measured in damaged and undamaged leaves as well as in the phloem to test how Si was allocated to different parts of the plant after damage. Localized, but not systemic, induction of Si defences occurred, and was more pronounced when plants had supplemental Si. Damaged plants had significant increases in Si concentration in their damaged leaves, while the Si concentration in undamaged leaves decreased, such that there was no difference in the average Si concentration of damaged and undamaged plants. The increased Si in damaged leaves was due to the redirection of soluble Si, present in the phloem, from undamaged to damaged plant parts, potentially a more cost-effective defence mechanism for plants than increased Si uptake.

Effect of Exogenous Tryptophan on Primary Metabolism and Oxidative Stress and Their Relationship with Seedling Germination and Vigor of Glycine Max L.

Treatments that increase the germination potential and vigor of Glycine max seedlings are continuously being stimulated, with the aim of achieving a higher percentage of emergence and better performance in the field. Considering the relationship of tryptophan with germination-associated phytohormones, this study tested the hypothesis that exogenous supply of tryptophan to soybean seeds can affect germination, physiological vigor, and the accumulation of primary and oxidative metabolism molecules in seedlings. Soybean seeds were exposed to soaking solutions containing different concentrations of the amino acid (0, 25, 50, 100, and 200 µM), and the seedlings were evaluated at three time periods, at 8 h after sowing (HAS), and 5 and 14 days after sowing (DAS). Treated seeds showed better germination fitness and seedlings showed greater vigor, and these parameters increased with increasing concentrations of tryptophan. In the initial hours and days of germination process evaluation (14 HAS and 5 DAS), the activities of starch metabolism enzymes (α- and β-amylase) tended to be higher, resulting in increased contents of sucrose, reducing sugars, and total soluble solids at 8 DAS, constituting an important metabolic effect for seedling growth. On the other hand, the induction of germination and vigor promoted by exogenous tryptophan in soybean seedlings occurred by stimulating the metabolic pathways of oxidative stress, resulting in increased concentrations of H2O2, malondialdehyde, and proline in the tissues. Additionally, it led to increased activities of the antioxidant enzymes superoxide dismutase and ascorbate peroxidase. These parameters were responsive to increasing supplied concentrations of tryptophan. Thus, the metabolic stress in soybean seeds induced by auxin seems to be an important inductive pathway for germination and vigor of G. max seeds.

Targeted mutagenesis of the vacuolar H+ translocating pyrophosphatase gene reduces grain chalkiness in rice.

Grain chalkiness is a major concern in rice production because it impacts milling yield and cooking quality, eventually reducing market value of the rice. A gene encoding vacuolar H+ translocating pyrophosphatase (V-PPase) is a major quantitative trait locus in indica rice, controlling grain chalkiness. Higher transcriptional activity of this gene is associated with increased chalk content. However, whether the suppression of V-PPase could reduce chalkiness is not clear. Furthermore, natural variation in the chalkiness of japonica rice has not been linked with V-PPase. Here, we describe promoter targeting of the japonica V-PPase allele that led to reduced grain chalkiness and the development of more translucent grains. Disruption of a putative GATA element by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 suppressed V-PPase activity, reduced grain chalkiness and impacted post-germination growth that could be rescued by the exogenous supply of sucrose. The mature grains of the targeted lines showed a much lower percentage of large or medium chalk. Interestingly, the targeted lines developed a significantly lower chalk under heat stress, a major inducer of grain chalk. Metabolomic analysis showed that pathways related to starch and sugar metabolism were affected in the developing grains of the targeted lines that correlated with higher inorganic pyrophosphate and starch contents and upregulation of starch biosynthesis genes. In summary, we show a biotechnology approach of reducing grain chalkiness in rice by downregulating the transcriptional activity of V-PPase that presumably leads to altered metabolic rates, including starch biosynthesis, resulting in more compact packing of starch granules and formation of translucent rice grains.

A specific H2/CO2 consumption molar ratio of 3 as a signature for the chain elongation of carboxylates from brewer's spent grain acidogenesis.

Brewer's spent grain (BSG) is an undervalorized organic feedstock residue composed of fermentable macromolecules, such as proteins, starch, and residual soluble carbohydrates. It also contains at least 50% (as dry weight) of lignocellulose. Methane-arrested anaerobic digestion is one of the promising microbial technologies to valorize such complex organic feedstock into value-added metabolic intermediates, such as ethanol, H2, and short-chain carboxylates (SCC). Under specific fermentation conditions, these intermediates can be microbially transformed into medium-chain carboxylates through a chain elongation pathway. Medium-chain carboxylates are of great interest as they can be used as bio-based pesticides, food additives, or components of drug formulations. They can also be easily upgraded by classical organic chemistry into bio-based fuels and chemicals. This study investigates the production potential of medium-chain carboxylates driven by a mixed microbial culture in the presence of BSG as an organic substrate. Because the conversion of complex organic feedstock to medium-chain carboxylates is limited by the electron donor content, we assessed the supplementation of H2 in the headspace to improve the chain elongation yield and increase the production of medium-chain carboxylates. The supply of CO2 as a carbon source was tested as well. The additions of H2 alone, CO2 alone, and both H2 and CO2 were compared. The exogenous supply of H2 alone allowed CO2 produced during acidogenesis to be consumed and nearly doubled the medium-chain carboxylate production yield. The exogenous supply of CO2 alone inhibited the whole fermentation. The supplementation of both H2 and CO2 allowed a second elongation phase when the organic feedstock was exhausted, which increased the medium-chain carboxylate production by 285% compared to the N2 reference condition. Carbon- and electron-equivalent balances, and the stoichiometric ratio of 3 observed for the consumed H2/CO2, suggest an H2- and CO2-driven second elongation phase, converting SCC to medium-chain carboxylates without an organic electron donor. The thermodynamic assessment confirmed the feasibility of such elongation.

ATB0,+-targeted nanoparticles initiate autophagy suppression to overcome chemoresistance for enhanced colorectal cancer therapy

Oxaliplatin (OXA) resistance remains the major obstacle to the successful chemotherapy of colorectal cancer (CRC). As a self-protection mechanism, autophagy may contribute to tumor drug resistance, therefore autophagy suppression could be regarded as a possible treatment option in chemotherapy. Cancer cells, especially drug-resistant tumor cells, increase their demand for specific amino acids by expanding exogenous supply and up-regulating de novo synthesis, to meet the needs for excessive proliferation. Therefore, it is possible to inhibit cancer cell proliferation through pharmacologically blocking the entry of amino acid into cancer cells. SLC6A14 (ATB0,+) is an essential amino acid transporter, that is often abnormally up-regulated in most cancer cells. Herein, in this study, we designed oxaliplatin/berbamine-coloaded, ATB0,+-targeted nanoparticles ((O + B)@Trp-NPs) to therapeutically target SLC6A14 (ATB0,+) and inhibit cancer proliferation. The (O + B)@Trp-NPs utilize the surface-modified tryptophan to achieve SLC6A14-targeted delivery of Berbamine (BBM), a compound that is found in a number of plants used in traditional Chinese medicine, which could suppress autolysosome formation though impairing autophagosome-lysosome fusion. We verified the feasibility of this strategy to overcome the OXA resistance during colorectal cancer treatment. The (O + B)@Trp-NPs significantly inhibited the proliferation and decreased the drug resistance of resistant colorectal cancer cells. In vivo, (O + B)@Trp-NPs greatly suppressed the tumor growth in tumor-bearing mice, which is consistent with the in vitro data. This research offers a unique and promising chemotherapeutic treatment for colorectal cancer.