Search Results (528)

The zinc finger protein 36 (ZFP36) family, including ZFP36/tristetraprolin (TTP), ZFP36 CCCH-type-like 1 (ZFP36L1), and ZFP36 CCCH-type-like 2 (ZFP36L2), consists of conserved CCCH-type tandem zinc-finger RNA-binding proteins. These proteins recognize AU-rich elements (AREs) in target mRNAs and promote deadenylation, decay, and translational repression. In this review, we use the term post-transcriptional immune checkpoint in a restricted conceptual sense: ZFP36 family proteins are intracellular, RNA-level negative regulators that tune the magnitude, duration, and resolution of immune effector programs, rather than classical receptor-ligand immune checkpoints such as programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). We summarize structural features, ARE-recognition mechanisms, mRNA decay pathways, translational repression mechanisms, and post-translational regulation of the ZFP36 family, while explicitly distinguishing mechanisms established for ZFP36 from those inferred for ZFP36L1 and ZFP36L2. We then review cell-type-specific roles in innate and adaptive immunity, including myeloid inflammatory responses, barrier tissue inflammation, innate lymphoid cell function, T cell activation and effector differentiation, regulatory T cell stability, B cell development, and antiviral immunity. In cancer, ZFP36 family members show context-dependent functions that should be separated into tumor-cell-intrinsic effects and immune-microenvironment-dependent effects. They suppress tumor progression by destabilizing pro-inflammatory, angiogenic, metabolic, and epithelial–mesenchymal transition (EMT)-associated transcripts, yet may also restrict antitumor immune responses or promote immune evasion in selected tumor contexts. Finally, we discuss autoimmune and inflammatory diseases, allergic disorders, transplant immunity, neuroimmune relevance, and therapeutic strategies, emphasizing the current evidentiary limits, preclinical status, and safety concerns of ZFP36 family modulation. Full article

Multi-effect evaporators are widely used in biomanufacturing to create concentrates of fermentation-derived products prior to or during crystallization, where the discharge concentration directly governs crystal product quality. However, bioprocess feed streams are subject to large and irregular disturbances arising from batch-to-batch fermentation variability and cell separation operations, making stable concentration control essential. In this study, a dynamic differential-algebraic model of a three-effect evaporator was developed, in which product composition evolves according to mass balance ordinary differential equations, while vapor and concentrate flows are determined algebraically from energy balances. Using this model, the discharge concentration was controlled against a representative feed composition disturbance scenario by comparing proportional–integral–derivative (PID) control with model predictive control (MPC). The PID controller failed to suppress the disturbance and exhibited sustained oscillations due to the large structural time delay and composition-dependent nonlinearity of the cascaded process. In contrast, the terminal-cost MPC predicted future behavior from the process model and compensated for disturbances preemptively, maintaining the discharge concentration almost exactly at its set point. The integrated absolute error decreased from 0.3872 for PID to 0.00145 for MPC with a 99.6% improvement. These results demonstrate that MPC enables robust product quality control in disturbance-rich biomanufacturing processes. Full article

Amino alcohols are a class of compounds bearing both amino and hydroxyl groups, ubiquitous in natural products and extensively utilized as key structural motifs in pharmaceuticals and functional materials. Owing to their structural diversity, inherent chirality, and high reactivity, they exhibit significant application value in the pharmaceutical field, materials industry, and organic synthesis. Compared with chemical synthesis, which suffers from limitations such as insufficient enantioselectivity, dependence on precious metal catalysts, and environmental concerns, biosynthesis offers core advantages of high stereoselectivity, mild reaction conditions, and environmental sustainability. This review systematically delineates the diverse applications of amino alcohols in the pharmaceutical field (e.g., anti-HIV, antimalarial, and antitumor drugs), materials industry (e.g., polymer modification and metal corrosion protection), and organic synthesis (e.g., chiral ligands and catalysts). Particular emphasis is placed on the biosynthetic strategies and pathways of representative amino alcohols, including ethanolamine, (2S,3R)-2-amino-1,3,4-butanetriol, (R)-3-amino-1-butanol, sphingosine, and metaraminol, as well as the metabolic engineering design principles and downstream processing technologies for amino alcohol biosynthesis. Although current biosynthetic approaches still face bottlenecks in enzyme catalytic efficiency, substrate tolerance, cofactor regeneration, product toxicity, and thermodynamic equilibrium, substantial improvements in synthetic efficiency and stereoselectivity have been achieved through protein engineering, metabolic engineering, in situ product removal, and multi-enzyme cascade optimization. This review aims to provide systematic theoretical references and technical insights for the green and efficient biomanufacturing of amino alcohols. Full article

Dioctyl adipate (DOA) and dioctyl sebacate (DOS) are widely used cold-resistance plasticizers; however, their low molecular weight and weak polarity result in poor thermal stability and migration resistance. Here, we report the synthesis and performance of bio-based cold-resistance plasticizers derived from trans-aconitic acid with enhanced migration resistance. Tri-n-butyl trans-aconitate (TBTA), tri-n-hexyl trans-aconitate (THTA), and tri-n-octyl trans-aconitate (TOTA) were synthesized via one-step esterification with aliphatic alcohols and applied in poly(vinyl chloride) (PVC). Compared with commercial plasticizers di-(2-ethylhexyl) phthalate (DEHP), tributyl citrate (TBC) and DOA, the synthesized plasticizers demonstrated excellent thermal stability and cold-resistance. After freezing treatment, the $T_g$ values of TBTA/PVC (18.99 °C) and THTA/PVC (20.88 °C) were lower than those of DEHP/PVC (22.74 °C). The branched architecture was supposed to strengthen interactions between plasticizers and PVC, improving volatility resistance and solvent extraction resistance. Compared with DOA/PVC at 48 h, TBTA/PVC, THTA/PVC and TOTA/PVC displayed volatility mass loss reduction of ~1.5%, 4% and 7%, respectively. Their extraction mass loss in ethanol decreased by 5–6%, while in petroleum ether, TBTA/PVC and TOTA/PVC dropped by 11.95% and 2.63%, respectively. These bio-based plasticizers are promising alternatives to the poor migration resistance of conventional low-temperature plasticizers. Full article

Stem cells, with their self-renewal and multi-lineage differentiation potential, hold promise for tissue repair and intractable diseases treatment. Yet clinical translation of stem cell therapies has long been hindered by insufficient scalable stem cell manufacturing, stemness loss and functional decline in 2D expansion, and poor post-transplantation cell retention, unregulated fate control. Programmable microcarriers (MCs) paired with 3D dynamic culture offer an emerging strategy to address these bottlenecks and enable stem cell fate regulation. In this review, we systematically review advanced MC fabrication strategies for stem cell fate regulation, comparing features of emerging technologies (microfluidics, electrospraying, in-air microfluidics, integrated in situ functionalization) and their implications for programmable MC control and scalable manufacturing. We analyze how MCs modulate stem cell behaviors (adhesion, proliferation, stemness maintenance, differentiation) via synergistic static physicochemical cues and dynamic stimuli-responsive properties. We map the latest advances in functionalized MC-mediated stem cell therapy across osteochondral defects, autoimmune, skin, ophthalmic and neurodegenerative diseases. Finally, we pinpoint unresolved challenges for clinical translation of MC–stem cell system and outline key future research directions. This review offers a systematic roadmap for advancing programmable MC fabrication, clinical-grade stem cell biomanufacturing, and precise cell therapy development. Full article

Continuous cropping obstacles (CCOs) seriously constrain tomato yield and quality in facility agriculture, primarily due to rhizosphere microbial imbalance. Indigenous synthetic microbial communities (SynCom) offer superior colonization and stability compared to single strains. This study aimed at constructing a simplified SynCom from indigenous rhizobacteria in Northwest China to alleviate tomato CCOs. A total of 155 rhizobacterial strains (29 genera) were isolated. Sixteen strains with significant growth-promoting effects were selected through seedling assays. Based on the carbon source niche overlap index (NOI > 70%) with Ralstonia solanacearum QL-Rs1115, eight candidate strains were retained. Using the broken-stick model, 29 simplified SynComs were constructed. SynCom28, composed of six functionally complementary strains (Azospirillum brasilense, Massilia niabensis, Enterobacter hormaechei, Chryseobacterium sp., Priestia megaterium and Pseudomonas brassicacearum), showed the best performance. Pot experiments revealed that SynCom28 reduced the bacterial wilt disease index to 32.41, with a biocontrol efficacy of 41.72%. Greenhouse trials under continuous cropping demonstrated that SynCom28 significantly increased seedling Dickson quality index (DQI), stem diameter and biomass. Fruit yield increased by 12.98–15.30% across the 2nd to 4th cropping cycles (p < 0.05). Fruit quality parameters were also enhanced, with soluble sugar, lycopene, and vitamin C contents increasing by 47.22–65.07%, 33.07–81.71% and 80.56–166.67%, respectively. In conclusion, the indigenous simplified SynCom28 effectively alleviates tomato CCOs, enhancing growth, yield, and quality while suppressing bacterial wilt, providing a promising strategy for sustainable facility agriculture. Full article

Global population growth and the demand for sustainable food systems have pushed microalgae into the spotlight as promising novel food resources. They are rich in protein, omega-3 fatty acids, and bioactive pigments including astaxanthin and phycocyanin. Unlike conventional farming, microalgae cultivation can be conducted on non-arable land and may reduce direct competition with conventional food crops for land resources, depending on the production system used. Regulatory progress in China, the European Union (EU), and the United States has resulted in the authorization or approval of several microalgal species and microalgae-derived ingredients for specific food and nutritional applications, including dietary supplements, infant nutrition products, and alternative protein ingredients. Despite these advances, broader commercial adoption remains constrained by several challenges, such as off-flavors and the dark green color, high production costs from closed photobioreactors and energy-intensive downstream purification, fragmented regulatory frameworks across jurisdictions and limited long-term data on bioavailability, allergenicity, safety, and dose–response relationships for some emerging strains. This review focuses on microalgae as novel food resources, covering regulatory approvals, strain selection, high-value utilization, and market translation, synthesizes evidence on nutritional evaluation, application scenarios, and global regulatory differences, analyzes key bottlenecks, and proposes pathways to bridge fundamental research with industrial practice. It also highlights unresolved knowledge gaps to guide future research and policy. Full article

Early-life microbial community assembly is important for gastrointestinal development, immune maturation, and feed utilization in young ruminants, but the maternal reservoirs associated with neonatal lamb gut microbial profiles remain insufficiently defined. This exploratory study characterized bacterial and archaeal communities in maternal vaginal secretions, amniotic fluid, and colostrum, together with rectal feces from Hu lambs at birth and at 5 days of age, using 16S rRNA gene amplicon sequencing in six matched ewe–lamb pairs. Alpha-diversity differences were evaluated using the Kruskal–Wallis test followed by pairwise Wilcoxon rank-sum tests where appropriate, beta-diversity was assessed by principal coordinate analysis based on Bray–Curtis distance, and discriminatory taxa were identified using LEfSe; statistical significance was defined as p < 0.05. Microbial community structure differed among sample types. Feces collected at birth showed low bacterial richness and a distinct community profile, whereas feces from 5-day-old lambs displayed higher bacterial richness and a more complex taxonomic composition. Shared-ASV and LEfSe analyses suggested that vaginal-associated taxa were more closely associated with the initial fecal microbiota at birth, while colostrum-associated taxa were more evident in day-5 feces. Archaeal communities showed weaker separation than bacterial communities, but methanogenic lineages became more distinguishable by day 5. These findings suggest that early gut microbial assembly in Hu lambs is associated with multiple maternal reservoirs and rapid postnatal ecological selection. However, due to the limited sample size, short observation period, lack of formal source-tracking analysis, and absence of low-biomass negative controls, the results should be interpreted cautiously as preliminary associations rather than definitive evidence of vertical transmission. Full article

The fast-growing cyanobacterium Synechococcus sp. PCC 11901 is emerging as a promising chassis for photosynthetic biomanufacturing. Here we report recombinant protein production in PCC 11901 via signal peptide-mediated secretion, enabling direct recovery of target proteins from the culture medium without cell disruption. Seven signal peptides spanning both Sec and Tat pathways are screened using eYFP as a reporter, with secretion quantified daily over seven days by fluorescence measurements. FutA, belonging to the Tat pathway from Synechocystis sp. PCC 6803, achieves 92.2% extracellular export by day 7, substantially outperforming all Sec candidates, including the best Sec signal peptide thermitase from Cyanobacterium aponinum PCC 10605 (55.7%). Signal peptide-bearing strains exhibit growth reductions of up to 26% relative to the wild-type, with FutA most affected, indicating a general metabolic cost correlated with secretion efficiency. The best-performing signal peptides from both pathways, FutA and thermitase, are validated with secretion of lichenase. Notably, the rank order of signal peptide performance is reversed for lichenase: thermitase demonstrates 2.6-fold higher extracellular activity than FutA, indicating that optimal signal peptide selection is cargo-dependent. These results establish PCC 11901 as a secretion-competent chassis and provide a rational framework for matching signal peptide pathways to target protein properties. Full article

Tissue engineering and regenerative medicine (TERM) rely on advanced biomaterials and scaffolds that require strict sterilization without sacrificing their structural and functional properties. Conventional sterilization methods, including steam, ethylene oxide, and gamma irradiation, often compromise scaffold integrity, alter surface chemistry and/or leave toxic residues. Ozone (O₃) has emerged as a promising alternative sterilant because of its strong oxidizing potential, broad-spectrum antimicrobial activity, and residue-free decomposition. Importantly, ozone sterilization can preserve—and in some cases enhance—scaffold bioactivity by maintaining cytocompatibility and favorable surface chemistries that support cell adhesion and differentiation. This review critically evaluates the role of ozone sterilization in the context of TERM applications, focusing on its physicochemical properties, disinfection kinetics, material compatibility and regulatory perspectives. Evidence from studies on polymethyl methacrylate (PMMA) scaffolds, bone implants, and hydrogel-based systems suggests that, under optimized conditions, ozone can achieve high sterilization efficacy without significant degradation of mechanical or chemical properties. However, challenges related to process validation, health and safety considerations, and scalability remain. The review highlights opportunities for integrating ozone into automated biomanufacturing workflows and identifies key research gaps to support the broader adoption of ozone sterilization in TERM applications. Full article

Synthetic biology seeks to build predictable, programmable biological systems. We developed a blue-light-inducible T7RNAP system with dual-input regulation to enable precise spatiotemporal gene control, which is vital for biomanufacturing, therapy, and microbial engineering. We optimized it by replacing RBS sequences, testing tandem T7 promoters, and evaluating split-T7RNAP variants. Expression and bactericidal efficacy were assessed via fluorescent output and real-time growth curves under blue light. RBS variants caused up to 50-fold differences in expression. Three tandem T7 promoters provided the best balance between yield and fidelity. Integration of a benzoate-responsive module enabled 4.5-fold repression at 3 mM benzoate, demonstrating effective chemical off-switching without compromising light induction. This system combines blue light precision with environmental responsiveness, offering non-invasive, on-demand activation for antimicrobial therapy or spatial bioproduction. The benzoate-triggered off-switch is especially valuable for ecological applications such as biocontainment or bioremediation, where gene expression must shut down upon detection of pollutants, for example, aromatic hydrocarbons. Its orthogonal, modular design supports context-dependent control, making it ideal for environmental biosensors, programmable probiotics, and smart antimicrobial delivery in complex ecosystems. Full article

Glycosylation is a critical structural modification that shapes the pharmacological properties of bioactive ingredients from Traditional Chinese Medicine (TCM), and UDP-glycosyltransferases (UGTs) are the core rate-limiting biocatalysts mediating this process. Traditional plant extraction methods are constrained by resource scarcity, long growth cycles, low target content and high environmental costs, which cannot meet the large-scale industrial demand for high-value medicinal glycosides. This review systematically outlines the latest global advances in medicinal plant UGT research, covering family classification and physiological functions, multi-omics and AI-assisted gene mining, molecular basis of substrate recognition and catalytic specificity, protein engineering for performance optimization, and the construction of full-spectrum biomanufacturing systems including in vitro multi-enzyme cascades, microbial cell factories and plant suspension cell cultures. We further discuss the core challenges of industrial scale-up, regulatory compliance and clinical translation, as well as the significant economic and technical advantages of synthetic biology-based UGT biomanufacturing platforms. This work provides a complete technical framework for the engineering application of medicinal plant UGTs, to support the green and scalable production of rare natural therapeutic glycosides. Full article

Vascular–osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises efficient bone repair. Gelatin methacryloyl (GelMA) hydrogels, which combine extracellular matrix-like bioactivity, adjustable mechanical properties, and compatibility with three-dimensional biomanufacturing, have become a widely used material platform for vascularized bone regeneration. From the perspective of vascular–osteogenic coupling, this review reframes and synthesizes GelMA-based approaches for vascularized bone regeneration, grouping existing strategies into three categories: (i) intrinsic material design, in which pore architecture, microchannels, dynamic networks, and interfacial functionalization are used to guide vascular ingrowth; (ii) exogenous bioactive delivery, involving growth factors, extracellular vesicles, cells, and inorganic ions to enhance vascularization; and (iii) smart responsive strategies, including ROS/pH-responsive systems, sequential release, and external stimulation, which aim to recapitulate the evolving microenvironment during bone repair. This review further compares these strategies in terms of evidence level, reproducibility, and translational potential. Exogenous delivery systems currently have the strongest preclinical support, but issues related to dose standardization, burst release, and long-term safety remain unresolved. Intrinsic material programming is less extensively studied, yet may be more compatible with manufacturing consistency, sterilization, and engineering translation. Most stimuli-responsive systems, by contrast, remain largely at the small-animal or proof-of-concept stage. Future GelMA-based systems should therefore shift from increasing functional complexity toward improving predictability, reproducibility, and clinical feasibility. Compositionally defined and structurally controllable GelMA composites that integrate vascular regulation with mechanical support may provide a more realistic path for vascularized bone regeneration. Full article

Background: Adenovirus-vectored vaccines played an important role in the global response to SARS-CoV-2. Adenovirus platforms have many advantages including a simple and readily transferred manufacturing process, low cost, and thermostability. Speed of production of an initial Good Manufacturing Practice (GMP)-compliant batch has, however, been viewed as a limitation of adenovirus vectors relative to mRNA platforms. Production of the initial viral starting material and release testing are key rate-limiting steps. Methods: Production of viral starting material from DNA, and release testing in accordance with regulatory expectations, for first-in-human trials of adenovirus-vectored vaccines. Results: We describe experience of these stages in the production of the first GMP batches for multiple adenovirus-vectored candidates and the adaptations made for ChAdOx1 nCoV-19 (the Oxford COVID-19 vaccine) in early 2020. We also report development of a streamlined approach to starting material generation, enabling initial GMP batch availability within c. 60 days of publication of a new pathogen sequence. Using a New World arenavirus vaccine construct as a proof of concept, we demonstrate reproducible execution of this pipeline, maintaining acceptable infectivity and other quality attributes. Conclusions: We discuss opportunities for additional time savings in the future. This work demonstrates suitability of an adenovirus platform to contribute to the “100 Days Mission” for vaccines against “Disease X”. Full article

Lignocellulosic biorefineries are limited by the high cost of cellulolytic enzymes. Consolidated bioprocessing (CBP), which integrates saccharification and fermentation in one step, offers a solution to this challenge. In this study, a cellulase-hyperproducing mutant of Talaromyces pinophilus, Y117, was generated from the parental strain TP117 via sequential ultraviolet irradiation and NTG (N-methyl-N′-nitro-N-nitrosoguanidine) mutagenesis. Enzymatic secretion and lignocellulose degradation capacities were evaluated, focusing on agricultural residues, particularly corncob. Y117’s performance was compared with TP117 and Trichoderma reesei Rut-C30 (TR30) under high-solids fermentation. Furthermore, the lactate dehydrogenase A (ldhA) gene from Rhizopus oryzae was heterologously expressed in Y117 to direct hydrolyzed sugars toward lactic acid (LA). Y117 exhibited significantly enhanced enzymatic secretion, achieving FPase activity of 8.9 IU/mL and a substrate utilization rate of 72.2% at 125 g/L corncob solids. Y117 outperformed TP117 and TR30 in cellulase, xylanase, and CMCase activities, as well as growth under high-solids fermentation conditions. In the LA fermentation process, Y117 produced 14.20 g/L LA, a notable improvement compared to TP117 (5.33 g/L) and TR30 (2.71 g/L). While LA productivity and yield currently remain below bacterial benchmarks, the unique CBP capability of Y117 provides a foundation for further metabolic engineering toward industrial viability. The engineered T. pinophilus Y117 demonstrates promising potential as a CBP platform for efficient straw-to-LA conversion, providing a sustainable approach for third-generation biobased materials production. Full article