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The hydrolysis and biotransformation of lignocellulose, i.e., biorefinery, can provide human beings with biofuels, bio-based chemicals, and materials, and is an important technology to solve the fossil energy crisis and promote global sustainable development. Biorefinery involves steps such as pretreatment, saccharification, and fermentation, and researchers have developed a variety of biorefinery strategies to optimize the process and reduce process costs in recent years. Lignocellulosic hydrolysates are platforms that connect the saccharification process and downstream fermentation. The hydrolysate composition is closely related to biomass raw materials, the pretreatment process, and the choice of biorefining strategies, and provides not only nutrients but also possible inhibitors for downstream fermentation. In this review, we summarized the effects of each stage of lignocellulosic biorefinery on nutrients and possible inhibitors, analyzed the huge differences in nutrient retention and inhibitor generation among various biorefinery strategies, and emphasized that all steps in lignocellulose biorefinery need to be considered comprehensively to achieve maximum nutrient retention and optimal control of inhibitors at low cost, to provide a reference for the development of biomass energy and chemicals.

Uric acid (UA) is mainly synthesized in the liver, intestine, and vascular endothelium and excreted by the kidney (70 %) and intestine (30 %). Hyperuricemia (HUA) occurs when UA production exceeds excretion. Many studies have found that elevated UA is associated with diabetic microvascular complications (DMC), including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). In addition, too high or too low UA levels will promote the occurrence and development of chronic diseases, but the relationship between UA and diabetic microvascular complications (DMC) is not clear. Therefore, the rational treatment of UA in patients with diabetes is essential. In this review, we summarize and discuss the mechanism and treatment of UA and DMC and may provide potential advice for rational drug selection. •SUA was closely related to diabetes and its complications.•Sodium-glucose cotransporter 2 (SGLT-2) could reduce the levels of SUA.•Dotinurad is a newer urate-lowering agent that suppresses UA reabsorption through the selective inhibition of URAT1 in the proximal renal tubules.

Summary Polyethylene terephthalate (PET) is a mass‐produced synthetic polyester contributing remarkably to the accumulation of solid plastics waste and plastics pollution in the natural environments. Recently, bioremediation of plastics waste using engineered enzymes has emerged as an eco‐friendly alternative approach for the future plastic circular economy. Here we genetically engineered a thermophilic anaerobic bacterium, Clostridium thermocellum, to enable the secretory expression of a thermophilic cutinase (LCC), which was originally isolated from a plant compost metagenome and can degrade PET at up to 70°C. This engineered whole‐cell biocatalyst allowed a simultaneous high‐level expression of LCC and conspicuous degradation of commercial PET films at 60°C. After 14 days incubation of a batch culture, more than 60% of the initial mass of a PET film (approximately 50 mg) was converted into soluble monomer feedstocks, indicating a markedly higher degradation performance than previously reported whole‐cell‐based PET biodegradation systems using mesophilic bacteria or microalgae. Our findings provide clear evidence that, compared to mesophilic species, thermophilic microbes are a more promising synthetic microbial chassis for developing future biodegradation processes of PET waste. Promising bioremediation strategies for plastics waste are of great importance and requirements. In our study, we constructed a recombinant Clostridium thermocellum strain expressing a secretory cutinase (LCC) as a thermophilic whole‐cell biocatalyst to degrade PET under high‐temperature condition (60°C). To our knowledge, this biocatalysis system demonstrates the highest PET degradation efficiency compared to reported whole‐cell‐based systems and also enjoys a low‐cost advantage over the free enzyme‐based process.

A novel amorphous Fe-doped manganese carbonate (a-FeMn-1) was synthesized via a facile co-precipitation method and evaluated as an efficient heterogeneous catalyst for the activation of peroxymonosulfate (PMS) in the degradation of Orange II. Among various Fe/Mn molar ratios, the 1:1 composition (a-FeMn-1) showed optimal catalytic activity, achieving 98% removal efficiency within 60 min under near-neutral pH conditions. Characterization results indicated that Fe doping effectively induced an amorphous structure and increased surface area and oxygen defects, promoting PMS activation. The system displayed broad pH applicability and resistance to Cl− and natural organic matter, while degradation was inhibited by HCO3− and PO43−. EPR and quenching experiments confirmed that surface-bound sulfate radicals (SO4•−), hydroxyl radicals (•OH), and singlet oxygen (1O2) were the primary reactive species. XPS analysis further revealed the redox cycling of Fe and Mn and the involvement of defect oxygen in the PMS activation process. The catalyst also demonstrated excellent reusability over five cycles without significant loss in efficiency. This work provides insights into the rational design of amorphous bimetallic materials for sulfate radical-based advanced oxidation processes.

Zygotic genome activation (ZGA) is the first transcription event in life 1 . However, it is unclear how RNA polymerase is engaged in initiating ZGA in mammals. Here, by developing small-scale Tn5-assisted chromatin cleavage with sequencing (Stacc–seq), we investigated the landscapes of RNA polymerase II (Pol II) binding in mouse embryos. We found that Pol II undergoes ‘loading’, ‘pre-configuration’, and ‘production’ during the transition from minor ZGA to major ZGA. After fertilization, Pol II is preferentially loaded to CG-rich promoters and accessible distal regions in one-cell embryos (loading), in part shaped by the inherited parental epigenome. Pol II then initiates relocation to future gene targets before genome activation (pre-configuration), where it later engages in full transcription elongation upon major ZGA (production). Pol II also maintains low poising at inactive promoters after major ZGA until the blastocyst stage, coinciding with the loss of promoter epigenetic silencing factors. Notably, inhibition of minor ZGA impairs the Pol II pre-configuration and embryonic development, accompanied by aberrant retention of Pol II and ectopic expression of one-cell targets upon major ZGA. Hence, stepwise transition of Pol II occurs when mammalian life begins, and minor ZGA has a key role in the pre-configuration of transcription machinery and chromatin for genome activation. Binding of RNA polymerase II during zygotic genome activation in mouse embryos is determined using the newly developed method Stacc–seq.

Arachidonic acid (ARA, 5, 8, 11, 14-cis-eicosatetraenoic acid) is a relevant ω-6 polyunsaturated fatty acid, which plays essential roles in human immune, cardiovascular, and nervous systems. It is widely used in medicine, cosmetics, nutrition, and other fields. Traditionally, ARA is obtained from animal tissues. However, due to the limitation and unsustainability of existing resources, microorganisms are a potential alternative resource for ARA production. In this regard, major efforts have been made on algae and filamentous fungi, among which Mortierella alpina is the most effective strain for industrial ARA production. In this review, we summarized the recent progress in enhancing M. alpina production by optimization of culture medium and fermentation process and genetic modification. In addition, we provided perspectives in synthetic biology methods and technologies to further increase ARA production.

Aurantiochytrium is a promising docosahexaenoic acid (DHA) production candidate due to its fast growth rate and high proportions of lipid and DHA content. In this study, high-throughput RNA sequencing technology was employed to explore the acclimatization of this DHA producer under cold stress at the transcriptional level. The overall de novo assembly of the cDNA sequence data generated 29,783 unigenes, with an average length of 1,200 bp. In total, 13,245 unigenes were annotated in at least one database. A comparative genomic analysis between normal conditions and cold stress revealed that 2,013 genes were differentially expressed during the growth stage, while 2,071 genes were differentially expressed during the lipid accumulation stage. Further functional categorization and analyses showed some differentially expressed genes were involved in processes crucial to cold acclimation, such as signal transduction, cellular component biogenesis and carbohydrate and lipid metabolism. A brief survey of the transcripts obtained in response to cold stress underlines the survival strategy of Aurantiochytrium ; of these transcripts, many directly or indirectly influence the lipid composition. This is the first study to perform a transcriptomic analysis of the Aurantiochytrium under low temperature conditions. Our results will help to enhance DHA production by Aurantiochytrium in the future.

Squalene is an important bioactive substance widely used in the food, pharmaceutical, and cosmetic industries. Microbial production of squalene has gained prominence in recent years due to its sustainability, safety, and environmental friendliness. In this study, a mutant strain, Pseudozyma sp. P4-22, with enhanced squalene-producing ability, was obtained through atmospheric and room temperature plasma mutagenesis of the previously screened squalene-producing yeast Pseudozyma sp. SD301. The P4-22 strain demonstrated the ability to produce squalene using various carbon and nitrogen sources. We optimized the culture conditions by employing cost-effective corn steep liquor as the nitrogen source, and the optimal pH and sea salt concentration of the medium were determined to be 5.5 and 5 g/L, respectively. Under optimal cultivation conditions, the biomass and squalene production reached 64.42 g/L and 2.06 g/L, respectively, in a 5 L fed-batch fermentation. This study highlights the potential of Pseudozyma sp. P4-22 as a promising strain for commercial-scale production of squalene.

Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial small molecules have been successfully used in enzyme engineering. The types of enzymatic reactions and metabolic pathways in cells can be expanded by the incorporation of these artificial small molecules either as cofactors or as building blocks of proteins and nucleic acids, which greatly promotes the development and application of biotechnology. In this review, we summarized research on artificial small molecules including biological metal cluster mimics, coenzyme analogs (mNADs), designer cofactors, non-natural nucleotides (XNAs), and non-natural amino acids (nnAAs), focusing on their design, synthesis, and applications as well as the current challenges in synthetic biology.

Bacterial σ I factors of the σ 70 -family are widespread in Bacilli and Clostridia and are involved in the heat shock response, iron metabolism, virulence, and carbohydrate sensing. A multiplicity of σ I paralogues in some cellulolytic bacteria have been shown to be responsible for the regulation of the cellulosome, a multienzyme complex that mediates efficient cellulose degradation. Here, we report two structures at 3.0 Å and 3.3 Å of two transcription open complexes formed by two σ I factors, SigI1 and SigI6, respectively, from the thermophilic, cellulolytic bacterium, Clostridium thermocellum . These structures reveal a unique, hitherto-unknown recognition mode of bacterial transcriptional promoters, both with respect to domain organization and binding to promoter DNA. The key characteristics that determine the specificities of the σ I paralogues were further revealed by comparison of the two structures. Consequently, the σ I factors represent a distinct set of the σ 70 -family σ factors, thus highlighting the diversity of bacterial transcription. Here the authors show that σ I factors encompass a unique, hitherto-unknown recognition mode of bacterial transcriptional promoters and represent a new distinctive class of σ 70 -family σ factors for bacterial transcription.