Synthesis Pathway Research Articles

Evaluation of a phenolic-tolerant Wickerhamomyces anomalus strain for efficient ethanol production based on omics analysis

Lignocellulosic biomass is a highly economically viable substrate for ethanol fermentation, but the presence of phenolic compounds (PCs) in lignocellulosic hydrolysates severely hinders the growth of ethanologenic strains. This study aims to investigate the ethanol fermentation capabilities and PC tolerance of the newly isolated Wickerhamomyces anomalus CAP5. The strain demonstrated remarkable ethanol production, achieving 87.1 g/L with a yield of 0.47 g/g, exceeding 90 % of the theoretical maximum. To elucidate the mechanisms responsible for this high ethanol yield, comprehensive genome and transcriptome analyses were performed. These analyses identified key metabolic pathways, including acetate reabsorption and an incomplete glycerol synthesis pathway, as crucial factors contributing to the strain's superior performance. Moreover, W. anomalus CAP5 demonstrated notable resistance to PCs, particularly phenolic acids. In fermenting with coffee husk hydrolysate (CHH), which is rich in PCs, W. anomalus CAP5 achieved noteworthy ethanol production of 60.5 g/L, marking a record for ethanol production from CHH. Hence, W. anomalus CAP5 emerges as a promising strain for effective ethanol production from lignocellulosic hydrolysates enriched with PCs.

Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges.

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro . In vivo , while deletion of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby metastatic cancer cells awake locally-generated developmental cues for metabolically reprograming, suggesting novel therapeutic approaches.

A sphingolipid rheostat controls apoptosis versus apical cell extrusion as alternative tumour-suppressive mechanisms

Evasion of cell death is a hallmark of cancer, and consequently the induction of cell death is a common strategy in cancer treatment. However, the molecular mechanisms regulating different types of cell death are poorly understood. We have formerly shown that in the epidermis of hypomorphic zebrafish hai1a mutant embryos, pre-neoplastic transformations of keratinocytes caused by unrestrained activity of the type II transmembrane serine protease Matriptase-1 heal spontaneously. This healing is driven by Matriptase-dependent increased sphingosine kinase (SphK) activity and sphingosine-1-phosphate (S1P)-mediated keratinocyte loss via apical cell extrusion. In contrast, amorphic hai1afr26 mutants with even higher Matriptase-1 and SphK activity die within a few days. Here we show that this lethality is not due to epidermal carcinogenesis, but to aberrant tp53-independent apoptosis of keratinocytes caused by increased levels of pro-apoptotic C16 ceramides, sphingolipid counterparts to S1P within the sphingolipid rheostat, which severely compromises the epidermal barrier. Mathematical modelling of sphingolipid rheostat homeostasis, combined with in vivo manipulations of components of the rheostat or the ceramide de novo synthesis pathway, indicate that this unexpected overproduction of ceramides is caused by a negative feedback loop sensing ceramide levels and controlling ceramide replenishment via de novo synthesis. Therefore, despite their initial decrease due to increased conversion to S1P, ceramides eventually reach cell death-inducing levels, making transformed pre-neoplastic keratinocytes die even before they are extruded, thereby abrogating the normally barrier-preserving mode of apical live cell extrusion. Our results offer an in vivo perspective of the dynamics of sphingolipid homeostasis and its relevance for epithelial cell survival versus cell death, linking apical cell extrusion and apoptosis. Implications for human carcinomas and their treatments are discussed.

UV-B irradiation promotes anthocyanin biosynthesis in the leaves of Lycium ruthenicum Murray.

Anthocyanins are the most valuable pigments in Lycium ruthenicum Murray (L.ruthenicum). Although ultraviolet-B (UV-B) irradiation is a key environmental factor influencing anthocyanin biosynthesis in L. ruthenicum, the deep molecular mechanism remains unclear. Herein, we examined the changes in the total anthocyanin content and transcriptomic characteristics of L. ruthenicum leaves following UV-B irradiation treatment. The results showed a twofold increase in anthocyanin content in the leaves of L. ruthenicum after the treatment. The transcriptome analysis showed that the expression of 24 structural genes identified in the anthocyanin synthesis pathway was up-regulated. In particular, F3'H (Unigene0009145) and C4H (Unigene0046607) exhibit notable up-regulation, suggesting their potential roles in anthocyanin synthesis. Protein interaction network results revealed that MYB1 (Unigene0047706) had the highest connectivity, followed by bHLH (Unigene0014085). Additionally, UVR8 (Unigene0067978) and COP1 (Unigene0008780) were found to be highly involved in UV-B signal transduction. These findings provide new insights into the genetic and biochemical mechanisms that regulate anthocyanin production, and could guide agricultural practices to reduce environmental impacts and improve crop yield and quality.

Trace Cu-Induced Low C─N Coupling Barrier on Amorphous Co Metallene Boride for Boosting Electrochemical Urea Production.

The electrochemical C─N coupling of carbon dioxide (CO2)and nitrate(NO3 -)is an alternative strategy to the traditional high-energy industrial pathway for urea synthesis, which urgently requires the design of efficient catalysts to achieve high yield and Faraday efficiency (FE). Here, amorphous low-content copper-doped cobalt metallene boride (a-Cu0.1CoBx metallene) is designed for urea synthesis via electrochemical C─N coupling. The a-Cu0.1CoBx metallene can drive electrocatalytic C─N coupling of CO2 and NO3 - for urea synthesis in CO2-saturated 0.1m KNO3 electrolyte, with 27.7% of FE and 312µgh-1mg-1 cat. of yield at -0.5V, as well as superior cycling stability. The in situ Fourier transform infrared and theoretical calculations reveal that electronic effect between Cu, Co, and B causes Cu and Co as dual active sites to promote the adsorption of reactants. Furthermore, the introduced trace Cu reduces the reaction energy barrier of the C─N coupling to facilitate urea synthesis. This work provides a promising route for the optimization of Co-based metallene for the electrosynthesis of urea through C─N coupling.

Characterization of CYP303A1 and its potential application based on ZIF-8 nanoparticle-wrapped dsRNA in Nilaparvata lugens (Stål).

RNA interference (RNAi) technology has been put forward as a promising method for pest control and resistance management. Mining highly efficient lethal genes and constructing stable double-stranded RNA (dsRNA) delivery systems are of great significance to improve the application potential of RNAi technology. In this study, we characterized a molting-related gene, NlCYP303A1, in Nilaparvata lugens that was highly expressed in the cuticle and at the end stages of each instar in nymphs. Silencing the expression of NlCYP303A1 in N. lugens resulted in a deformed phenotype and a significant increase in mortality. Furthermore, interfering with NlCYP303A1 changed the relative expression of key genes in the chitin synthesis and degradation pathway. Finally, we used the nanocarrier zeolitic imidazolate framework-8 (ZIF-8) to load dsNlCYP303A1, forming a complex denoted as dsNlCYP303A1@ZIF-8. The results of both feeding and rice-seedling dip experiments indicated that the expression of NlCYP303A1 was dramatically and persistently suppressed by the dsNlCYP303A1@ZIF-8 treatment, compared with treatment with dsNlCYP303A1, suggesting that ZIF-8 can enhance the interference efficiency as well as the stability of dsNlCYP303A1. Our results demonstrate that the lethal gene NlCYP303A1 can be employed as an excellent target for RNAi technology by loading onto a nano-delivery system, and provide new insights into the creation of innovative pest control approaches. © 2024 Society of Chemical Industry.

The molecular insights of cyanobacterial bioremediations of heavy metals: the current and the future challenges.

In recent years, overexplorations of ore and the growth of industries are the prime factors in the release of heavy metals in environments. As a result, the food crops and water bodies are contaminated with metals which may have several adverse effects on the health of humans and other living species. These metals and metalloids, such as Zn, Cu, Mn, Ni, Cr, Pb, Cd, and As, upset the biochemical pathways of metabolite synthesis in living organisms and contribute to the etiology of different diseases. Microorganisms include bacteria, archaea, viruses, and many unicellular eukaryotes, which can span three domains of life-Archaea, Bacteria, and Eukarya-and some microorganisms, such as cyanobacteria, have shown high efficiency in the biosorption rate of heavy metals. Cyanobacteria are suitable for bioremediation as they can grow in adverse environments, have a less negative impact on the surrounding environment, and are relatively cheaper to manage. The structure of cyanobacteria has shown no extensive internal-bound membranes, so it can directly employ the physiological mechanisms to uptake heavy metals from contamination sites. Such biochemical makeups are suitable for managing and bioremediating heavy metal concentrations in polluted environments. This review aims to explore the potential of cyanobacteria in the bioremediation of heavy metals and metalloids in water bodies. Additionally, we have identified the prospects for enhancing bioremediation effectiveness.

TRANSPARENT TESTA 16 collaborates with the MYB-bHLH-WD40 transcriptional complex to produce brown fiber cotton.

Naturally colored cotton (NCC; Gossypium spp.) does not require additional chemical dyeing and is an environmentally friendly textile material with great research potential and applications. Our previous study using linkage and association mapping identified TRANSPARENT TESTA 2 (Gh_TT2) as acting on the proanthocyanin synthesis pathway. However, limited information is available about the genetic regulatory network of NCC. Here, we verified the effectiveness of Gh_TT2 and the roles of Gh_TT2 and red foliated mutant gene (Re) in pigment formation and deposition of brown fiber cotton (BFC). Variations in Gh_TT2 derived from interspecific hybridization between Gossypium barbadense acc. Pima 90-53 and Gossypium hirsutum acc. Handan208 resulted in gene expression differences, thereby causing phenotypic variation. Additionally, the MYB-bHLH-WD complex was found to be negatively modulated by TRANSPARENT TESTA 16/ARABIDOPSIS BSISTER (TT16/ABS). RNA-seq suggested that differential expression of homologous genes of key enzymes in the proanthocyanin synthesis pathway strongly contributes to the color rendering of natural dark brown and light brown cotton. Our study proposes a regulatory model in BFC, which will provide theoretical guidance for the genetic improvement of NCC.

Shading increases the susceptibility of alfalfa (Medicago sativa) to Pst. DC3000 by inhibiting the expression of MsIFS1

Shade is a stressful factor for most plants, leading to both morphological and physiological changes, and often resulting in increased susceptibility to diseases and pathogen attacks. Our study revealed that the isoflavonoid synthesis pathway was inhibited in alfalfa under shade, resulting in a significant reduction in disease resistance. Overexpression of MsIFS1, a switch regulator in isoflavonoid synthesis, led to a notable increase in endogenous isoflavonoids and enhanced resistance to Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000). Conversely, MsIFS1-RNAi had the opposite effect. Yeast one-hybrid (Y1H) assays revealed that the shade-responsive transcription factor MsWRKY41 could directly bind to the MsIFS1 promoter. This interaction was confirmed through Dual-Luciferase Reporter (Dual-LUC) and Chromatin Immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) assays, both in vitro and in vivo. Overexpression of MsWRKY41 not only enhanced alfalfa's resistance to Pst. DC3000 but also promoted the accumulation of isoflavonoids. Additionally, yeast two-hybrid (Y2H) assays showed that neither MsWRKY41 nor MsIFS1 physically interacted with the Type III effector (T3SE) HopZ1 secreted by Pst. DC3000, suggesting that the MsWRKY41-MsIFS1 module is not a direct target of HopZ1. These findings provide valuable theoretical insights and genetic resources for the development of shade-tolerant alfalfa with enhanced disease resistance.

Multiomics Reveals a Mechanism: Glycogen Synthesis, Galactose Metabolism, and Ethanol Degradation Pathways, the Durable Role of Neutralizing Antibodies in Preventing COVID-19.

Since the emergence and rapid dissemination of Coronavirus disease 2019 (COVID-19), over 774 million individuals globally have achieved recovery to today. There is some case flashing into here and there all over the world. Neutralizing Antibody (NAb) against Severe Acute Respiratory Syndrome Coronavirus-Type 2 (SARS-CoV-2) play a paramount role in conferring effective and lasting protection for several months. This protective effect decreases with time thus increasing the chance of reinfection. Therefore, we can provide the body with a lasting protective effect by maintaining NAb level. However, how to maintain Nab level remains elusive. To address this question, we recruited 80 patients with confirmed COVID-19 and collected 480 consecutive blood samples and performed NAb testing six months after their recovery. The NAb level were categorized into two groups: a low-titer NAb group (≤20) and a high-titer NAb group (>20). To achieve a comprehensive understanding of the changes in NAb level, 16 serum samples were randomly selected for an untargeted metabolomic analysis, whereas 9 samples were designated for a label-free proteomic analysis. We successfully identified differentially expressed 751 metabolites and 845 proteins. In both the low and high NAb titer groups, we identified three key differential proteins, phosphoglucose translocase 2(PGM2), UDP-Glc 4-epimerase (GALE), and alcohol dehydrogenase 1B (ADH1B), that play important roles in fluctuating NAb level through the glycogen synthesis, galactose metabolism and ethanol degradation pathways. These three key differential proteins may serve as potential biomarkers for maintaining NAb level and enhancing immune protection in patients recovering from COVID-19.

Continuous Theta Burst Stimulation Inhibits Oxidative Stress-Induced Inflammation and Autophagy in Hippocampal Neurons by Activating Glutathione Synthesis Pathway, Improving Cognitive Impairment in Sleep-Deprived Mice.

Sleep deprivation (SD) has been reported to have a negative impact on cognitive function. Continuous theta burst stimulation (cTBS) shows certain effects in improving sleep and neurological diseases, and its molecular or cellular role in SD-induced cognition impairment still need further exploration. In this study, C57BL/6 mice were subjected to 48h of SD and cTBS treatment, and cTBS treatment significantly improved SD-triggered impairment of spatial learning and memory abilities in mice. Additionally, cTBS reduced malondialdehyde levels, increased superoxide dismutase activities, and inhibited the production of inflammatory cytokines, alleviating oxidative stress and inflammation levels in hippocampal tissues of SD model mice. cTBS decreased LC3II/LC3I ratio, Beclin1 protein levels, and LC3B puncta intensity, and elevated p62 protein levels to suppress excessive autophagy in hippocampal tissues of SD-stimulated mice. Then, we proved that inhibiting oxidative stress alleviated inflammation, autophagy, and death of hippocampal neuron cells through an in vitro cellular model for oxidative stress, and cTBS treatment promoted the production of glutathione (GSH), the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expression of GSH synthesis-related genes to enhance antioxidant capacity in hippocampal tissues of SD mice. An Nrf2 inhibitor ML385 or a GSH synthesis inhibitor BSO reversed the alleviating effects of cTBS treatment on oxidative stress-associated damage of hippocampal tissues and cognitive impairment in SD model mice. Altogether, our study demonstrated that cTBS mitigates oxidative stress-associated inflammation and autophagy through activating the Nrf2-mediated GSH synthesis pathway, improving cognitive impairment in SD mice.

Efficient Catalytic Conversion of Acetate to Citric Acid and Itaconic Acid by Engineered Yarrowia lipolytica

The bioconversion of agricultural and industrial wastes is considered a green and sustainable alternative method for producing high-value biochemicals. As a major catalytic product of greenhouse gases and a by-product in the fermentation and lignocellulose processing industries, acetate is a promising bioconversion raw material. In this work, endogenous and heterologous enzymes were manipulated in Yarrowia lipolytica to achieve the conversion of acetate to high-value citric acid and itaconic acid, respectively. After the combinational expression of the key enzymes in the acetate metabolic pathway, the citric acid synthesis pathway, and the mitochondrial transport system, acetate could be efficiently converted to citric acid. Coupled with the down-regulation of fatty acid synthase expression in the competitive pathway, more acetyl-CoA flowed into the synthesis of citric acid, and the titer reached 15.11 g/L with a productivity of 0.51 g/g acetate by the engineered Y. lipolytica, which is comparable to the results using glucose as the substrate. On this basis, the heterologous cis-aconitate decarboxylase from Aspergillus terreus was introduced into the engineered Y. lipolytica to achieve the catalytic synthesis of itaconic acid from acetate. Combined with investigating the effects of multiple enzymes in the synthesis pathway, the titer of itaconic acid reached 1.87 g/L with a yield of 0.43 g/g DCW by the final engineered strain, which is the highest reported titer of itaconic acid derived from acetate by engineered microbes in shake flasks. It is demonstrated that acetate has the potential to replace traditional starch-based raw materials for the synthesis of high-value organic acids and our work lays a foundation for the rational utilization of industrial wastes and the catalytic products of greenhouse gases.

Unraveling abiotic organic synthesis pathways in the mafic crust of mid-ocean ridges

The aqueous alteration of the oceanic lithosphere provides significant energy that impacts the synthesis and diversity of organic compounds, which are crucial for the deep carbon cycle and may have provided the first building blocks for life. Although abiotic organic synthesis has been documented in mantle-derived rocks, the formation mechanisms and complexity of organic compounds in crustal rocks remain largely unknown. Here, we show the specific association of aliphatic carbonaceous matter with Fe oxyhydroxides in mafic crustal rocks of the Southwest Indian Ridge (SWIR). We determine potential Fe-based pathways for abiotic organic synthesis from CO2 and H2 using multimodal and molecular nano-geochemical tools. Quantum mechanical modeling is further employed to constrain the catalytical activity of Fe oxyhydroxides, revealing that the catalytic cycle of hydrogen may play a key role in carbon-carbon bond formation. This approach offers the possibility of interpreting physicochemical organic formation and condensation mechanisms at an atomic scale. The findings expand our knowledge of the existence of abiotic organic carbon in the oceanic crustal rocks and emphasize the mafic oceanic crust of the SWIR as a potential site for low-temperature abiotic organic synthesis.

Advancing Sustainability: Geraniol-Enhanced Waterborne Acrylic Pressure-Sensitive Adhesives without Chemical Modification.

The escalating global emphasis on sustainability, coupled with stringent regulatory frameworks, has spurred the quest for environmentally viable alternatives to petroleum-derived materials. Within this context, the adhesives industry has been actively seeking renewable options and eco-friendly synthesis pathways. This study introduces geraniol, a monoterpenoid alcohol, in its unmodified form, as a key component in the production of waterborne pressure-sensitive adhesives (PSAs) based on acrylic latex through emulsion polymerization. Multiple formulations were developed at varying reaction times. The adhesives underwent comprehensive chemical characterization employing techniques such as Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Nuclear Magnetic Resonance (NMR), Gel Permeation Chromatography (GPC), and dynamic light scattering (DLS). The viscosities of the formulations were measured between 4000 and 5000 cP. Adhesion tests showed peel strength values of 0.52 N/mm on cardboard and 0.32 N/mm on painted steel for the geraniol-based formulations. The results demonstrate the potential for geraniol-based PSAs to offer a sustainable alternative to petroleum-derived adhesives, with promising thermal and adhesive properties.

Replacement of fish meal with defatted black soldier fly (Hermetia illucens) in diet of Pacific white shrimp (Litopenaeus vannamei): growth, flesh quality and transcriptome

Abstract This study evaluated the impacts of replacing fish meal (FM) with defatted black soldier fly (Hermetia illucens; BSF) on the growth performance, flesh quality and transcriptome of Pacific white shrimp (Litopenaeus vannamei). In a diet containing 560 g/kg FM, BSF was used to replace 0%, 20%, 40%, 60%, 80% and 100% of dietary FM (BSF0, BSF20, BSF40, BSF60, BSF80 and BSF100). Thus, six isonitrogenous and isolipidic diets were prepared, and then fed to juvenile Pacific white shrimp (1.70 ± 0.10 g) for 60 days. In growth performance, the BSF20 group showed the similar FCR and WGR to the control group (), and the other four BSF groups presented significantly lower WGR and higher FCR than the BSF0 group (). The flesh chewiness and the contents of crude lipid, collagen and total amino acid in flesh were significantly decreased (), and flesh cooking loss, thawing loss was significantly increased when the replaced FM was ≥40% (). When the replaced FM reached 60%, the flesh hardness, heat-insoluble collagen content, shear force, body surface redness and the ratio of n-3/n-6 fatty acids were significantly lower (), while n-6 polyunsaturated fatty acid content and total free amino acid content in flesh were significantly higher than those of the BSF0 group (). Hepopancreatic samples were used for transcriptomic analysis, and a total of 1,456 differentially expressed genes (DEGs) were identified between the BSF groups and BSF0 group, which were mainly involved in growth-promoting, energy metabolism and antioxidant capacity key pathways and genes, including the cathepsin L, folate synthesis pathway, redox-related genes and glutathione metabolism pathway. In conclusion, in a diet containing 560 g/kg FM, BSF could successfully replace 20% of dietary FM, and higher FM replacement (≥40%) decreased the growth performance and flesh quality of Pacific white shrimp.

Engineering a novel pathway for efficient biosynthesis of salicin in Escherichia coli

Salicin is a natural glycoside compound widely used to treat fever, inflammation, and analgesia. Currently, salicin is primarily extracted from willow bark, which is not only cumbersome in terms of extraction and separate steps, but also subject to seasonal and geographic limitations. In this study, a highly efficient biosynthetic pathway for salicin synthesis was designed and constructed in E. coli. The most important precursor in the synthetic pathway of salicin designed in this study is salicyl alcohol. Building on a previously constructed biosynthetic salicylic acid metabolic pathway, the production of salicyl alcohol in shake flask fermentation reached 1.7 g/L by increasing the supply of shikimic acid pathway precursor PEP and salicyl alcohol precursor chorismate. According to the principle of substrate similarity, this study identified the key enzyme OsSGT1 from Oryza sativa, which uses E. coli endogenous UDP-glucose as a glycosyl donor to glycosylate salicyl alcohol into salicin. By redefining the optimal substrate of OsSGT1, and balancing metabolic flux along with increasing the supply of UDP-glucose, salicin production in shake flasks reached 4 g/L. Finally, culturing the high-yield strain in a 3-L fermenter resulted in the synthesis of 14.62 g/L of salicin. To the best of our knowledge, this achievement marks the highest salicin production through microbial fermentation to date.

Hydrogen peroxide participates in leaf senescence by inhibiting CHLI1 activity.

Hydrogen peroxide promoted leaf senescence by sulfenylating the magnesium chelating protease I subunit (CHLI1) in the chlorophyll synthesis pathway, and inhibited its activity to reduce chlorophyll synthesis. Leaf senescence is the final and crucial stage of plant growth and development, during which chlorophyll experiences varying degrees of destruction. It is well-known that the higher ROS accumulation is a key factor for leaf senescence, but whether and how ROS regulates chlorophyll synthesis in the process are unknown. Here, we report that H2O2 inhibits chlorophyll synthesis during leaf senescence via the I subunit of magnesium-chelatase (CHLI1). During leaf senescence, the decrease of chlorophyll content is accompanied by the increase of H2O2 accumulation, as well as the inhibition of catalase (CAT) genes expression. The mutant cat2-1, with increased H2O2 shows an accelerated senescence phenotype and decreased CHLI1 activity compared with the wild type. H2O2 inhibits CHLI1 activity by sulfenylating CHLI1 during leaf senescence. Consistent with this, the chli1 knockout mutant displays the same premature leaf senescence symptom as cat2-1, while overexpression of CHLI1 in cat2-1 can partially restore its early senescence phenotype. Taken together, these results illustrate that CAT2-mediated H2O2 accumulation during leaf senescence represses chlorophyll synthesis through sulfenylating CHLI1, and thus inhibits its activity, providing a new insight into the pivotal role of chlorophyll synthesis as a participant in orchestrating the leaf senescence.

Fe3+ Assisted Synthesis of Stable 3D‐in‐2D CsPbBr3/CsPb2Br5 Nanocomposites for Optical Gain Media

AbstractMetal halide perovskite nanocrystals are sought after for many optical and optoelectronic applications, such as light‐emitting diode and solar cells, due to their outstanding optical properties. However, their ionic nature makes them susceptible to ambient conditions. One rational solution to this challenge is the passivation or encapsulation of perovskite nanocrystals to isolate them from their environments. Thus, there is an urgent need to develop efficient methods for encapsulating emissive perovskite nanocrystals. A facile post‐synthesis method is proposed to treat CsxFA(1−x)PbBr3 nanocrystals, in the presence of Fe3+ cations, to create a robust and water‐stable nanocomposite structure, where 3D CsPbBr3 nanocrystals are embedded in and thus protected by the 2D CsPb2Br5 nanosheets (named as CsPbBr3/CsPb2Br5 hereafter). These Fe3+ cations facilitate the formation of the CsPbBr3/CsPb2Br5 composite and regulate the growth of 2D CsPb2Br5 sheets. By performing controlled experiments, the possible mechanism of 2D nanosheet growth is proposed and discussed in detail. More importantly, the composite can remain stable in water for three months and exhibits amplified spontaneous emission under femtosecond laser irradiation. This work presents a synthesis pathway for producing durable perovskite composites that are promising for future lasing applications.

Chromosome-Scale Genome and Transcriptomic Analyses Reveal Differential Regulation of Terpenoid Secondary Metabolites in Hericium coralloides.

Construction of the genome of Hericium coralloides, a species of edible mushroom, and identification of the genes involved in terpenoid biosynthesis can determine the biology and genetics of terpenoids. The present study describes the assembly of a high-quality chromosome-scale genome of H. coralloides using Pacbio HiFi sequencing and Hi-C technology. This genome consisted of 13 chromosomes, a total size of 43.6 Mb, contigs of N50 3.6 Mb, GC content at 54%, and BUSCOs integrity of 96.9%. Genes associated with terpenoid biosynthesis were predicted by KEGG enrichment analysis and homologous alignment. The Her011461 and Her008335 genes, encoding proteins in the terpenoid backbone synthesis pathway, were found to encode geranylgeranyl pyrophosphate and farnesyl diphosphate synthases, key enzymes in the biosynthesis of geranylgeranyl diphosphate, a precursor of several diterpenoids. Her011463 was found to be involved in regulating diterpene cyclase. The Her005433, Her006724, Her010605, and Her010608 genes were found to encode sesquiterpene synthesis. Most of these genes were more highly expressed in dikaryotic mycelia than in the primordium and fruiting bodies, indicating that terpenoids may be more abundant in dikaryotic mycelia. To our knowledge, this study is the first to assemble the H. coralloides genome at the chromosome scale and to identify the genes involved in terpenoid biosynthesis.

MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma.

Group 3 medulloblastoma (MBGRP3) represents around 25% of medulloblastomas and is strongly associated with c-MYC (MYC) amplification, which confers significantly worse patient survival. Although elevated MYC expression is a significant molecular feature in MBGRP3, direct targeting of MYC remains elusive, and alternative strategies are needed. The metabolic landscape of MYC-driven MBGRP3 is largely unexplored and may offer novel opportunities for therapies. To study MYC-induced metabolic alterations in MBGRP3, we depleted MYC in isogenic cell-based model systems, followed by 1H high-resolution magic-angle spectroscopy (HRMAS) and stable isotope-resolved metabolomics, to assess changes in intracellular metabolites and pathway dynamics. Steady-state metabolic profiling revealed consistent MYC-dependent alterations in metabolites involved in one-carbon metabolism such as glycine. 13C-glucose tracing further revealed a reduction in glucose-derived serine and glycine (de novo synthesis) following MYC knockdown, which coincided with lower expression and activity of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in this pathway. Furthermore, MYC-overexpressing MBGRP3 cells were more vulnerable to pharmacological inhibition of PHGDH compared to those with low expression. Using in vivo tumor-bearing genetically engineered and xenograft mouse models, pharmacological inhibition of PHGDH increased survival, implicating the de novo serine/glycine synthesis pathway as a pro-survival mechanism sustaining tumor progression. Critically, in primary human medulloblastomas, increased PHGDH expression correlated strongly with both MYC amplification and poorer clinical outcomes. Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.