Microbial biocatalysis spans biological platforms ranging from purified enzymes and multienzyme assemblies to electroenzymatic systems, whole-cell biocatalysts, and genetically programmable microbial cell factories. Yet despite their biological diversity, functional biocatalytic performance is often influenced by both catalytic activity and molecular accessibility. This recurring constraint highlights molecular accessibility as a common engineering consideration across microbial biocatalysis. Accordingly, this Review presents the concept of molecular access engineering as the rational control of molecular accessibility to improve functional biocatalytic performance across biological scales. The concept encompasses three complementary strategies governing molecular entry, intermediate transfer, and molecular exchange throughout biological systems. Examples from gas-converting enzymes, multienzyme assemblies, electroenzymatic systems, catalytic cascades, whole-cell biocatalysts, and microbial cell factories illustrate how engineering molecular accessibility can improve catalytic robustness, pathway efficiency, biological compatibility, and systems-level productivity. These examples therefore suggest that molecular access engineering has the potential to broaden the design space for microbial biocatalysis by complementing catalytic engineering.
Against the backdrop of emerging engineering education and in response to the discrepancy between rapid industrial growth and the shortage of innovative talent supply, the bioengineering program at Northwest University has systematically restructured its innovative talent cultivation model. Guided by industry development trends and regional industrial upgrading, the program integrates science with engineering through the outcome-based education (OBE) philosophy of student-centeredness, output-orientation, and continuous improvement. We have established a comprehensive training model oriented toward the biomanufacturing industrial chain and characterized by a three-level, four-module, and five-dimensional guidance framework. This model integrates hierarchical training (basic, comprehensive, and innovative), practical modules (basic skills, professional skills, innovative experiments, and social practice), and a five-dimensional mentorship system comprising counselors, class sponsors, academic tutors, entrepreneurship mentors, and enterprise mentors. Supported by a robust teaching quality assurance system, this initiative has fostered a new educational ecosystem that deeply incorporates research with teaching and integrates production, education, research, and application. This model provides a valuable reference for talent cultivation and professional development in local universities. 在新工科建设背景下，针对生物工程产业快速发展与创新型人才供给不足的矛盾，西北大学生物工程专业以人为本，以行业发展趋势为指引，紧密结合区域经济发展和产业转型升级需要，系统开展了创新人才培养模式的改革与实践。通过深化理工交叉融合，秉承“学生中心、产出导向、持续改进”的产出导向教育(outcome-based education, OBE)理念，构建了以生物制造全产业链为导向的创新人才培养模式。基于“基础型、综合型、创新型”三个层次，“基本技能、专业技能、创新实验、社会实践”四大模块，“辅导员、班主任、学业导师、创业竞赛导师、企业实践导师制”五个维度引导的培养机制，并辅以系统性的教学质量保障体系，建立了科研与教学深度融合、产学研用协同育人的新型教育生态。该模式为地方高校人才培养和专业发展提供了参考。.
Since its experimental realization in 2004, graphene has revolutionized materials science due to its extraordinary two-dimensional (2D) architecture and exceptional physicochemical properties. Graphene oxide (GO), a pivotal derivative of graphene, exhibits immense potential for multifunctional nanocomposites, attributed to its unique 2D framework, abundant surface functional groups, and excellent solution processability. This review establishes structural engineering as the foundational paradigm for designing graphene-based nanocomposites with integrated multifunctionality. We systematically examine how structural engineering governs multiscale architectures from atomic-level defect configurations to macroscopic assembly geometries and elucidate the underlying structure-property relationships through mechanistic frameworks including phonon transport theory, percolation theory, and composite micromechanics. In-depth analyses of multifunctional applications in mechanical engineering, electronics, energy storage, environmental remediation, and biomedicine are presented, with explicit attention to both demonstrated advantages and persistent limitations of each application category. Critically, we identify and analyze four key industrialization bottlenecks, including structural controllability, batch consistency, scale effects, and cost-effectiveness trade-offs that currently impede the transition from laboratory achievements to scalable manufacturing. By synthesizing existing research findings with industrialization considerations, this review offers a critical assessment of the field's current state and provides actionable theoretical guidance and technical pathways for the precise design and large-scale industrialization of graphene-based nanocomposites.
Staphylococcus haemolyticus is an emerging multidrug-resistant nosocomial pathogen noted for robust biofilm formation and complex restriction-modification (RM) systems that hinder genetic manipulation. These barriers have severely limited mechanistic studies into its pathogenesis and immune evasion. Here, we report the development of a molecular toolbox that enables precise genomic engineering of clinical S. haemolyticus isolates. Using PacBio Single-Molecule Real-Time and bisulfite sequencing, we defined the complete genomes and methylomes of nine isolates, generating a functional readout of the active RM defences present in each strain. Among the RM systems identified, a Type II (PDLC03279) and a Type III (PDL3649/PDLC03643) system were significantly overrepresented in clinical isolates, suggesting a potential role in adaptation to host or hospital-associated environments. To bypass these RM barriers, we implemented a dual strategy: first, applying SyngenicDNA-based approaches to eliminate RM target motifs from genetic tools and second, engineering a surrogate Escherichia coli strain (JMC4) to mimic conserved S. haemolyticus methylation patterns. These tools significantly enhanced transformation efficiency and enabled targeted knockout of four putative virulence genes (sraP, secA2, capA and capI) as well as allelic exchange of the native capsule operon with the corresponding region from a non-encapsulated isolate. To our knowledge, this is the first report of precise genomic modifications in S. haemolyticus. The establishment of robust molecular tools for transformation and genome editing lays a foundation for future functional studies of virulence and host adaptation in this resilient opportunistic pathogen.
Aqueous zinc-ion batteries have broad application prospects in large-scale energy storage owing to their high safety, low cost, and environmental compatibility. However, Zn metal anodes still suffer from dendrite growth, hydrogen evolution, corrosion, and interfacial side reactions, which severely limit cycling stability. As a key component connecting the electrolyte and electrode interfaces, the separator has gradually evolved from a conventional physical barrier into a functional layer for regulating Zn2+ transport, water state, and interfacial reactions. Cellulose separators have attracted extensive attention in aqueous zinc-ion batteries because of their abundant resources, renewability, good hydrophilicity, tunable pore structure, and facile chemical modification. This review focuses on functional-group-engineered cellulose separators, highlighting the structural features, advantages, and potential limitations of hydroxyl-rich, carboxylated, sulfonated, and amino-functionalized cellulose separators. The interfacial regulation mechanisms involving Zn2+ coordination and flux homogenization, anion exclusion and selective transport, water-activity regulation, and side-reaction suppression are further discussed. Finally, future directions, including precise functional-group design, fast ion-channel construction, green scalable fabrication, and standardized device-level evaluation, are proposed to provide guidance for the design of highly stable separators for aqueous zinc-ion batteries.
Mesenchymal stem cell -derived exosomes (MSCs-EXO) have been increasingly studied due to their high biosafety and excellent drug delivery properties. The use of MSCs-EXO as drug carriers for the treatment of rheumatoid arthritis (RA) has been reported. However, conventional exosomes cannot target the damaged area, significantly reducing their therapeutic efficacy. Therefore, this study proposes a strategy for the rational design of exosomes derived from genetically engineered mesenchymal stem cells, enabling them to target the inflammatory storm in the affected limb, regulate the immune microenvironment, and release similar to superoxide dismutase (SOD-like) and similar to catalase (CAT-like) nanoparticles to eliminate Reactive Oxygen and Nitrogen Species (RONS). RA provides a therapeutic platform for disease repair. MSC transduced with a lentivirus and carrying the anchoring peptide IL-4Rα secrete exosomes containing this peptide (IL-4.EXO), which demonstrates excellent targeting ability. These exosomes encapsulate Prussian blue nanoparticles (PB@IL-4.EXO), forming a synergistic composite exosome delivery system targeting inflammation sites, antioxidant stress, and promoting cartilage joint repair. Micro-CT shows a reduction in cartilage damage. Proteomics confirmed that it inhibits inflammation by affecting the proteasomal pathway through suppression of the PSMD4 protein. This exosome combines regulation of inflammation and antioxidant stress, offering a new therapeutic strategy for RA.
As advanced electronic components become more miniaturized and integrated, the performance requirements for polymer dielectric films are becoming increasingly stringent. Although the aromatic polymer polyetherimide (PEI) exhibits excellent thermal stability, the π-π conjugated structures present in its main chain tend to enhance electron delocalization and intermolecular charge transfer, leading to a significant increase in conductance loss under high-temperature conditions, which limits further improvements in its energy storage performance. In contrast to the previously documented trap-modulation strategies, this study proposes an innovative dual-end synergistic modulation strategy that targets both the molecular backbone and terminal groups. The introduction of highly polar sulfone groups into the PEI backbone, in conjunction with 4-phenylacetylene phthalic anhydride (PEPA) into the terminal groups, resulted in the construction of a cross-linked network structure. This process has been shown to enhance the polarization response of the PEI film, whilst concomitantly creating deep-level charge traps. Surprisingly, at an elevated temperature of 150 °C, the characteristic breakdown field strength of SPEI 10%-PEPA was determined to be 575 MV m-1, representing a 15% increase in comparison with the uncross linked SPEI. Concurrently, an ultra-high energy storage density of 4.64 J cm-3 was attained, accompanied by a charge-discharge efficiency that surpassed 90%.
Aortic aneurysms, including thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA), represent a group of severe vascular lesions with insidious onset and high mortality. Currently, effective diagnostic markers and pharmacological interventions remain lacking in clinical practice. Extracellular vesicles (EVs), as key mediators of intercellular communication, have attracted increasing attention in the research on aortic aneurysms due to their high content of bioactive molecules, favorable biocompatibility, low immunogenicity, and inherent targeting capacity. This review systematically elaborated on the research progress on EVs in TAA and AAA, highlighting their significant role in the development and progression of aortic aneurysms. EVs play a crucial role by mediating core pathological processes, including endothelial dysfunction, phenotypic transformation of vascular smooth muscle cells, inflammatory immune responses, and extracellular matrix remodeling. Additionally, this review discussed the potential of disease-specific molecules carried by EVs as novel liquid biopsy markers for the early diagnosis of aortic aneurysms. Furthermore, this review evaluated the application prospects of EVs as natural drug delivery platforms and EV-based therapeutic strategies for aortic aneurysm through engineering modifications (such as targeting peptide modification and biomaterial integration). In particular, "cell-free" immunomodulatory therapies, which enhance targeting capacity to lesion sites through engineering modifications and focus strategically on regulating the phenotype and function of key immune cells (such as macrophages), are increasingly emerging as a cutting-edge direction with the greatest translational potential in this field. Despite challenges such as targeted delivery, the integration of engineering technologies with nanomedicine holds promise for opening new avenues for the precise prevention and treatment of aortic aneurysms through EV-based integrated diagnostic and therapeutic strategies. 主动脉瘤包括胸主动脉瘤(thoracic aortic aneurysm, TAA)和腹主动脉瘤(abdominal aortic aneurysm, AAA)，是一类发病隐匿且致死率高的严重血管病变，目前临床上尚缺乏有效的诊断标志物及药物干预手段。细胞外囊泡(extracellular vesicles, EVs)是细胞间通讯的关键介质，因其携带丰富的生物活性分子且具备良好的生物相容性、低免疫原性和天然靶向性，在主动脉瘤相关研究中日益受到关注。本文系统阐述了EVs在TAA和AAA中的研究进展，重点总结了EVs在主动脉瘤发生发展中的重要作用。EVs通过介导内皮功能障碍、血管平滑肌细胞表型转换、炎症免疫反应及细胞外基质重塑等核心病理过程发挥重要作用。同时，本文探讨了EVs携带的疾病特异性分子在主动脉瘤早期诊断中展现出作为新型液体活检标志物的潜力。此外，还评估了EVs作为天然药物递送平台及基于工程化修饰(如靶向肽修饰、生物材料结合)的主动脉瘤治疗策略的应用前景，尤其是通过工程化修饰增强其对病变部位的靶向能力，以调控关键免疫细胞(如巨噬细胞)表型与功能为策略核心的“无细胞”免疫调节疗法，日益成为该领域最具转化潜力的前沿方向。尽管面临靶向递送等挑战，但随着工程化技术与纳米医学的融合，基于EVs的诊疗一体化策略有望为主动脉瘤的精准防治开辟新路径。.
The applied courses at regional universities face common industry-education disconnect problems, including course contents lagging behind industrial technological advancements, mismatches between practical training and job competency requirements, and underdeveloped industry-education collaboration mechanisms. To address these problems, this study explores teaching reform practices driven by industry-education integration for Biotechnological Pharmaceutics. Focusing on the drug R&D and production process, we developed an education system featuring five-dimensional integration (concept-mechanism-structure-mode-process) that embeds industrial standards throughout the teaching process. For content restructuring, industrial elements such as engineered cell lines and production protocols were introduced and transformed into design of experiments (DOE)-based tasks, which effectively converted industrial requirements into teaching components. For teaching mode innovation, a "four-in-one" (online resources, offline instruction, laboratory centers, and enterprise platforms) teaching ecosystem was established to guide students through the "design-build-test-learn" engineering cycle via a "virtual-physical combination and university-enterprise alternation" approach. For assessment reform, a "dual-track (emphasizing both process and outcome evaluation), three-stage (before, in, and after class)" quantitative assessment system involving the participation of enterprise mentors was established to align assessment standards with talent demands. After the reform, the proportion of students with excellent and good grades increased significantly, and the interview success rate improved. A number of students were employed by partner enterprises. Moreover, students won multiple awards in provincial-level or higher discipline competitions. The results indicated that the course objective achievement was steadily enhanced. This practice provides an industry-education integration framework for biopharmaceutical courses and serves as an example for regional universities in cultivating talents for developing new quality productive forces. 针对地方高校应用型课程普遍存在的教学内容滞后于产业技术发展、实践环节与岗位能力要求不匹配、产学协同机制不健全等产教脱节问题，本文以“生物技术制药”课程为例，探索产教融合驱动的教学改革实践。课程以药品研发生产流程为教学主线，构建了涵盖“理念-机制-架构-模式-过程”这5个维度的融合育人体系，将产业标准贯穿于教学过程。在课程内容重构方面，引入工程细胞株与生产工艺等真实企业要素，并据此开展基于实验设计(design of experiments, DOE)理念的教学任务设计，实现产业要求向教学要素的系统转化;在教学模式创新方面，依托“四位一体”教学平台(线上资源库/线下教学/实验中心/企业平台)，采用“虚实结合、校企交替”的教学组织形式，引导学生实践“设计-构建-测试-学习”的工程循环;在考核评价改革方面，建立由企业导师深度参与的“双轨三阶”的量化评价机制(兼顾过程与结果评价，覆盖课前、课中、课后)，推动考核标准与用人需求的有效对接。实践结果表明，改革后学生成绩优良率显著提升，面试成功率较往届明显增长，多名学生入职合作企业，并在省级以上科创竞赛中屡获佳绩，课程目标达成度稳步提高。本实践为生物医药类课程提供了可推广的产教融合范式，对地方高校新质生产力人才培养具有参考价值。.
The optical properties of quantum systems are fundamentally governed by their electromagnetic environment through the local density of optical states (LDOS), enabling powerful control over atomic, excitonic, and electronic transitions. However, the radiative properties of phonons have remained largely unexplored within this framework of environmental engineering. Here we demonstrate LDOS control of terahertz (THz) phonon emission in the van der Waals ferroelectric NbOI2 using a simple mirror geometry. By modifying the photonic environment, we achieve pronounced and reversible tuning of the phonon Q-factor, peak frequency, linewidth, and emission intensity, with modulation approaching an order of magnitude. The observed behavior arises from Purcell-like enhancement and suppression of the phonon radiative rate, revealing a near-unity radiative quantum efficiency in NbOI2. Our results establish radiative phonons as tunable quasiparticles governed by photonic boundary conditions, extending LDOS engineering from electronic to lattice excitations. This framework enables deterministic control of phonon lifetimes and emission spectra, opening new opportunities for compact tunable THz sources and phonon-based quantum and photonic technologies.
Antimicrobial resistance (AMR) is a global health crisis, and multidrug-resistant ESKAPE pathogens pose a significant threat to current treatments. Antibody therapy is a promising antibacterial strategy to combat AMR, but the inherent instability and limited functional diversity of biological antibacterial antibodies hinder the development of universal therapies. Here, we report the chemically engineered gold-based bifunctional antibody biomimetic (AuriFAB), which achieves universal antimicrobial therapy against all multidrug-resistant ESKAPE pathogens. By utilizing dithiocarbamate ligation, AuriFAB attains exceptional colloidal stability under harsh biological conditions and long-term storage stability exceeding one year in solution. Chemical epitope screening identifies a disulfiram-engineered AuriFAB that features a bispecific Fab-mimicking recognition mechanism, targeting FtsZ in Gram-positive bacteria and lipopolysaccharide in Gram-negative bacteria, unlocking picomolar binding affinity and enabling nanogram-per-milliliter antibacterial efficacy. AuriFAB demonstrates low toxicity, high selectivity, favorable pharmacokinetics, and in vivo metabolizable clearance. This chemical strategy addresses the stability and functionality limitations of biological antibacterial antibodies and provides a universal solution to combat AMR, demonstrating the therapeutic potential of chemistry-driven biologic mimics.
Inflammatory osteoporosis is a metabolic bone disease characterized by chronic inflammation-induced disruption of bone homeostasis, and its alleviation requires intervention strategies capable of effectively modulating the inflammation-associated bone microenvironment. This study employed genetic engineering techniques to construct recombinant Saccharomyces boulardii strains capable of secreting Hypophthalmichthys molitrix cystatin C (HmCys C), and preliminarily evaluated the efficacy of different dosages of strains in modulating inflammatory osteoporosis. Four recombinant plasmids, designated pSF-TEF1-αMF-HmCys C, pSF-TEF1-STA1-HmCys C, pSF-TDH3-SED1-HmCys C, and pSF-TDH3-CL-HmCys C, incorporating distinct promoter-signal peptide combinations, were designed. Following electroporation, four corresponding recombinant yeast strains (MC, TC, EC, and LC) were successfully constructed, as confirmed by PCR identification and sequencing analysis. Tricine-SDS-PAGE and Western blotting results demonstrated that strains MC and EC successfully secreted HmCys C with an apparent molecular weight of 12.44 kDa. The corresponding inhibitory activities were (56.07±3.82)% and (35.85±1.15)%, respectively. Relative quantification results indicated that the expressed HmCys C accounted for (24.31±0.40)% and (15.15±0.94)% of the total protein in strains MC and EC, respectively. Characterization of the in vitro characteristics of strains MC and EC revealed morphological alterations-including cell collapse, surface roughness, and irregular contours-compared with the wild-type strain. However, the growth profiles showed minimal changes (P>0.05). The cell surface hydrophobicity of strain MC increased to (21.54±4.18)% (P<0.05), whereas the auto-aggregation of strain EC decreased to (49.72±2.91)% (P<0.05). Under various stress conditions (pH 1.0‒7.0, bile salt concentration of 0.1%‒2.0%, and 37‒60 ℃), both MC and EC strains exhibited excellent tolerance to acidic pH [survival rate≥(88.18±3.80)%] and bile salts [survival rate≥(86.95±0.39)%]. In contrast, their thermotolerance was comparatively lower, and strains MC and EC showed the survival rates of (37.50±1.91)% and (37.16±0.22)%, respectively, after exposure to 60 ℃. After sequential exposure to simulated salivary, gastric, and intestinal fluids, the survival rates of all the strains declined progressively but remained above (78.71±4.33)%, indicating robust tolerance to gastrointestinal stresses. Hemolysis assays confirmed that neither the recombinant strains secreting HmCys C nor the wild-type strain induced hemolytic activity. Finally, a murine model of lipopolysaccharide (LPS)-induced inflammatory osteoporosis was established. Oral gavage with strain MC at the medium dosage resulted in an increase in bone mineral density (P<0.05). In conclusion, this study successfully constructed S. boulardii strains secreting HmCys C and revealed their in vitro characteristics. The medium-dosage group demonstrated potential regulatory effects on inflammatory osteoporosis. These findings provide a foundation for further probing into the underlying mechanisms and efficacy, contributing experimental data towards developing probiotic-based intervention strategies for the prevention of osteoporosis. 炎症性骨质疏松是一种由慢性炎症导致骨稳态失衡的代谢性骨病，为开发能有效调节炎症相关骨微环境的干预策略，缓解疾病症状，本研究采用基因工程手段构建分泌鲢鱼cystatin C (HmCys C)的重组布拉迪酵母，并初步评估不同剂量酵母在炎症性骨质疏松调节中的效果。设计了含4种启动子-信号肽组合的重组质粒，即pSF-TEF1-αMF-HmCys C、pSF-TEF1-STA1-HmCys C、pSF-TDH3-SED1-HmCys C、pSF-TDH3-CL-HmCys C，经电转化、PCR鉴定、测序分析确定成功构建4株对应重组酵母菌株MC、TC、EC、LC。Tricine-SDS-PAGE及Western blotting分析表明，菌株MC、EC可分泌HmCys C蛋白，表观分子量为12.44 kDa，对应抑制活性分别为(56.07±3.82)%、(35.85±1.15)%;相对定量结果表明，MC、EC菌株表达的HmCys C蛋白占比分别为(24.31±0.40)%、(15.15±0.94)%。菌株MC、EC的体外特性分析结果显示，相较野生型，重组菌株呈现细胞塌陷、表面粗糙和轮廓不规则的形态学变化，但生长性能变化较小(P>0.05);菌株MC的细胞疏水性显著提升至[(21.54±4.18)%, P<0.05]，而EC的自聚性降至[(49.72±2.91)%, P<0.05]。在不同条件下(pH 1.0‒7.0、胆盐浓度0.1%‒2.0%、温度37‒60 ℃)，菌株MC、EC均表现出优异的pH [存活率≥(88.18±3.80)%]及胆盐[存活率≥(86.95±0.39)%]耐受性;而对高温的耐受性较低，在60 ℃时菌株MC、EC的存活率分别为(37.50±1.91)%、(37.16±0.22)%。经模拟唾液、胃液、肠液连续消化，各菌株存活率呈现下降趋势，但均保持在(78.71±4.33)%以上，具有较强胃肠道压力耐受能力。溶血实验证实分泌HmCys C蛋白的重组菌株及野生型酵母均无溶血效应。最后，构建脂多糖诱导的炎症性骨质疏松小鼠模型，经3种剂量的MC菌株灌胃后，中剂量组骨密度显著提升(P<0.05)。本研究成功构建了分泌HmCys C的布拉迪酵母并明确了其体外特性，中剂量组菌株在炎症性骨质疏松中表现出调控潜力，实验结果为后续深入探究调控效果及机制奠定基础，为建立预防骨质疏松的益生菌干预策略提供了实验依据。.
Pressure-sensitive adhesives (PSAs) underpin modern technologies, yet their sustainability is fundamentally constrained by the same molecular features that enable rapid bonding and durable adhesion. In particular, carbon-carbon-dominated backbones confer desirable viscoelastic properties but lead to persistent materials that are difficult to remove, recycle, or dismantle after use. Here, we review recent progress in PSA sustainability and frame it as a lifecycle design challenge, in which feedstock origin, polymer architecture, adhesive function, and end-of-life behavior must be considered together. We show that current approaches-bio-based materials, degradable structures, and debonding strategies-each address different stages of the adhesive lifecycle and exhibit distinct advantages and limitations when pursued independently. Emerging hybrid systems demonstrate that these functions can be integrated, enabling on-demand debonding and downstream transformation without compromising adhesive performance, even under stringent application constraints. This perspective suggests that sustainable PSAs should be designed not through single-axis optimization, but through lifecycle programmability, where bonding, release, and post-use fate are co-engineered according to the intended reuse, recycling, or recovery pathway.
Nanozyme-based nanomotors have shown significant potential in biomedical applications, particularly in catalytic tumor therapy, due to their stability and autonomous propulsion capabilities. However, their therapeutic efficacy is limited by diffusion barriers within dense tumor tissues and low catalytic efficiency in the mild tumor microenvironment. Herein, Ag2S-decorated mesoporous silica-coated CeVO4-based near-infrared-powered nanorockets were designed and synthesized for enhanced-penetrating synergistic photothermal-catalytic tumor therapy. In this construct, the CeVO4 core acts as a redox-active chemical engine within the permeable silica shell, facilitating glutathione depletion and reactive oxygen species (ROS) generation from endogenous H2O2. The anchored Ag2S nanoparticles endow the nanorockets with the capability of NIR-driven self-propulsion behavior via active thermophoresis. Under NIR irradiation, the localized heat drives the nanorockets to overcome diffusion barriers and reach internal tumor reservoirs. Simultaneously, this thermal effect accelerates catalytic reaction kinetics, thereby establishing a self-sustaining therapeutic loop. This approach addresses the limitations of poor tissue penetration and low functional coupling, providing a motility-enhanced, self-amplifying anti-tumor strategy.
The precise construction of high-energy catalytic interfaces is often impeded by the thermal inertia of conventional synthesis, where thermodynamic equilibrium leads to the agglomeration of nanostructures and the relaxation of metastable active sites. Herein, we report a strategy of nano-interfacial engineering enabled by shape anisotropy-driven magnetothermal synergy to overcome these limitations. Unlike traditional heating techniques, we introduce NiCo2O4 nanoneedles as active magnetothermal antennas, leveraging their specific shape anisotropy to maximize magnetic coupling via enhanced Néel relaxation. This geometric design induces localized, ultrafast thermal shocks (heating rate ∼13.6 °C s-1) directly at the reaction interface. Consequently, the in situ grown nitride electrocatalysts achieve a kinetic locking of metastable Co3+ species and preserve the pristine nanostructured morphology, which are otherwise lost in equilibrium processing. The resulting catalyst delivers a superior oxygen evolution overpotential of 289 mV at 100 mA cm-2, significantly outperforming thermodynamic equilibrium-controlled counterparts. Additionally, the system demonstrates robust overall water splitting performance (1.66 V at 10 mA cm-2). This work fundamentally decouples material synthesis from global thermal constraints, presenting magnetic induction not merely as a heating tool, but as a novel field-matter interaction medium for the benign-by-design construction of advanced energy interfaces.
A bifunctional ether-ester additive (LMEO) is rationally engineered to simultaneously modulate the Zn2+ solvation structure and interfacial microenvironment in aqueous zinc batteries. the reconstructed interfacial chemistry effectively suppresses water-induced parasitic reactions, homogenizes Zn deposition behavior, and inhibits dendritic growth, enabling enhanced Zn reversibility and cycling durability over wide-temperature range.
Fatty acid synthase (FASN) is a key enzyme catalyzing the de novo biosynthesis of fatty acids. Its aberrant overexpression in multiple tumor types is closely correlated with tumor invasiveness and poor prognosis, making it a critical target for anti-cancer drug development. However, existing small-molecule inhibitors targeting the catalytic domains of FASN frequently encounter challenges such as high target homology and considerable off-target risk. To explore novel regulatory sites with higher specificity, this study targeted the highly dynamic acyl carrier protein (ACP) domain of FASN for nanobody selection, aiming to evaluate and validate its feasibility as a potential therapeutic target. Initially, utilizing a yeast surface-display nanobody library (with a capacity of 1×108), two rounds of magnetic-activated cell sorting (MACS) and one round of fluorescence-activated cell sorting (FACS) were performed, and 18 nanobodies targeting the ACP domain were obtained. Subsequently, their binding affinities were verified using surface plasmon resonance (SPR) assays. Finally, the inhibitory effects of these nanobodies on FASN activity were further characterized using both cell-free and cell-based activity assays, combined with fusion to the cell-penetrating peptide TAT. The results demonstrated that several nanobodies exhibited distinct binding activity to the target protein, with affinities reaching the nanomolar range. Among them, NbB-11 exhibited the most potent inhibitory activity toward FASN, achieving a 28.2% inhibition rate of FASN in vitro activity at a concentration of 3 μmol/L. Furthermore, the TAT-NbB-11 fusion protein, constructed by linking NbB-11 with the cell-penetrating peptide TAT, was successfully delivered across the membrane and demonstrated a 22.0% cell proliferation inhibition rate at a concentration of 4 μmol/L. In conclusion, this study successfully selected high-affinity nanobodies targeting FASN and preliminarily validated the feasibility of the ACP domain as a regulatory target for FASN activity. These findings provide fundamental lead molecules for subsequent nanobody engineering and in vivo validation. 脂肪酸合成酶(fatty acid synthase, FASN)是催化脂肪酸从头合成的关键酶，其在多种肿瘤中的异常高表达与肿瘤侵袭性及不良预后密切相关，是抗肿瘤药物开发的重要靶点。然而，现有针对FASN催化结构域的小分子抑制剂常面临靶点同源性高、潜在脱靶风险大等挑战。为寻找更具特异性的新型调控位点，本研究以FASN高度动态的酰基载体蛋白(acyl carrier protein, ACP)结构域为靶标开展纳米抗体筛选，旨在评估并验证其作为潜在调控靶点的可行性。首先，利用纳米抗体酵母表面展示库(库容量1×108)进行2轮磁珠分选和1轮流式筛选，筛选并获得了18种靶向ACP的纳米抗体。其次，使用表面等离子共振实验验证其结合能力。最后，使用细胞内外活性检测方法并通过与穿膜肽TAT融合，进一步表征纳米抗体对FASN活性的抑制效果。结果表明，多株纳米抗体与靶蛋白具有明确的结合活性，亲和力达纳摩尔级别。其中，NbB-11对FASN抑制活性表现最佳，在3 μmol/L浓度下对FASN体外活性的抑制率为28.2%。此外，通过与穿膜肽TAT融合构建的TAT-NbB-11蛋白成功实现了跨膜递送，在4 μmol/L浓度下表现出22.0%的细胞增殖抑制率。本研究成功淘选出靶向FASN的高亲和力纳米抗体，初步验证了ACP结构域作为FASN活性调控靶点的可行性，为后续的纳米抗体工程化改造及体内验证提供了基础先导分子。.
Thaumatin is a natural sweet-tasting protein derived from the plant Thaumatococcus daniellii, renowned for its high sweetness intensity, low caloric value, and favorable thermal and pH stability. As it can be degraded into natural amino acids, thaumatin represents a potentially safer alternative sweetener. However, plant-based extraction of this protein is constrained by low endogenous content, as well as geographical and seasonal limitations. Meanwhile, existing microbial cell factories often struggle to simultaneously achieve high expression levels and ensure high product purity with natural conformation. To address this bottleneck, this study designed and constructed a thaumatin precursor protein (pThaumatin) incorporating an affinity purification tag and a traceless cleavage site. Using Pichia pastoris as the expression host, the folding and secretory expression efficiency of this precursor protein was enhanced through engineering of the protein folding and secretion pathways in the cell factory, combined with fed-batch fermentation. Following affinity chromatography purification, 126 mg of high-purity thaumatin precursor protein was obtained per liter of fermentation broth. Subsequent downstream processing using residue-free protease cleavage enabled the removal of the fusion tag, yielding mature thaumatin (mThaumatin) with a sequence identical to that of the native protein, achieving a conversion efficiency of nearly 100%. The resulting protein exhibited secondary structure consistent with that of native thaumatin. Circular dichroism spectroscopy revealed that the thaumatin protein released by enzymatic cleavage exhibited high consistency in secondary structure with native thaumatin. Preliminary sensory evaluation confirmed that the protein displayed a pronounced sweet taste, indicating function integrity. This study establishes a technical pipeline encompassing "precursor protein design-cell factory secretory expression-traceless enzymatic post-processing" for the production of high-purity, native-conformation thaumatin via microbial fermentation. This study provides a reference for achieving high-purity expression and the restoration of the native conformation of sweet-tasting proteins. 索马甜(thaumatin)是一种源于植物丹尼尔奇异果(Thaumatococcus daniellii)的天然甜味蛋白，具有高甜度、低热量、较好的热稳定性与pH稳定性。索马甜可降解为天然氨基酸，是更安全的潜在甜味剂。植物提取该蛋白质面临含量低、作物区域及季节限制等问题，现有微生物细胞工厂通常难以在提高表达量的同时，保证产物的高纯度与天然构象。为解决这一问题，本研究设计并构建了一种融合亲和纯化标签与无痕切除位点的索马甜前体(pThaumatin)蛋白。以毕赤酵母作为表达宿主，通过改造细胞工厂折叠分泌蛋白质的过程与分批补料发酵，提升前体蛋白的折叠与分泌表达效率。经过亲和层析纯化，每升发酵液获得了126 mg高纯度索马甜前体蛋白。随后通过下游无残留蛋白酶切处理去除融合标签，获得与天然序列完全一致的成熟索马甜蛋白(mThaumatin)，转化率接近100%。圆二色谱分析表明，酶切释放所得的索马甜蛋白在二级结构上与天然索马甜高度一致。初步感官评估证实该蛋白甜味显著，功能正常。本研究建立了一条“蛋白质前体设计-细胞工厂分泌表达-无痕酶切后处理”的技术路线，实现了基于微生物发酵的高纯度、天然构象索马甜的制备，为实现甜味蛋白的高纯度表达及天然构象恢复提供了参考。.
Complex energy electrocatalytic reactions, such as CO2 reduction, nitrogen conversion reactions, and C-N coupling, are promising pathways for sustainable energy conversion and green chemical synthesis. However, their efficiency and selectivity are fundamentally limited by adsorption-energy scaling relationships and functional constraints of conventional single-site catalysts. Inspired by biological enzyme systems, this review summarizes the emerging "decoupling-integration" strategy for addressing these challenges. By constructing spatially separated yet functionally interconnected active sites within heterointerfaced nanostructures, complex reaction pathways can be divided into independently optimized elementary steps while maintaining efficient communication between spatially separated catalytic functions. Such architectures enable tandem catalysis, local microenvironment regulation, interfacial charge redistribution, and cooperative pathway control, thereby significantly enhancing catalytic activity, selectivity, and stability. Representative heterointerfaced architectures, including Janus nanostructures, core-shell systems, supported heterojunctions, and hierarchically integrated composite heterostructures, are systematically discussed. Their structural characteristics, catalytic mechanisms, and advantages in regulating intermediate adsorption, accumulation, transport, and conversion are highlighted through representative studies of CO2 reduction, nitrogen conversion, C-N coupling, and related multistep electrocatalytic reactions. Particular emphasis is placed on how interfacial engineering and spatial functional compartmentalization help overcome kinetic mismatches, suppress side reactions, and break scaling-relation limitations. Finally, current challenges and future perspectives are discussed, including operando mechanistic characterization, atomic-level interfacial regulation, catalyst stability under industrial conditions, data-driven catalyst design, and expansion toward other complex electrosynthetic reactions.
Radiotherapy can reshape the tumor microenvironment by promoting the polarization of tumor-associated macrophages (TAMs) toward either an antitumor (M1-like) phenotype or an immunosuppressive (M2-like) phenotype that facilitates tumor progression. To evaluate the modulatory effects of the fusion antioxidant enzyme GS1XR on macrophage polarization under radiotherapy-associated conditions, we used hydrogen peroxide (H2O2) to establish an oxidative stress model in RAW264.7 macrophages. The cytotoxicity, intracellular reactive oxygen species (ROS) scavenging capacity, and cellular uptake efficiency were compared among GS1, GS1R, and GS1XR. Subsequently, two macrophage polarization reporter cell lines-RAW-PNos2-P (for M1-like polarization) and RAW-PArg1-P (for M2-like polarization)-were employed to assess the effects of the three fusion antioxidant enzymes, as well as N-acetylcysteine (NAC), on macrophage polarization induced by H2O2, transforming growth factor beta 1 and conditioned medium from irradiated nasopharyngeal carcinoma cells. The results showed that 200 μmol/L H2O2 significantly increased intracellular ROS levels with minimal impact on cell viability. GS1R and GS1XR exhibited stronger membrane permeability than GS1, and none of the three enzymes showed notable cytotoxicity at the working concentrations. Across all the three polarization-inducing models, antioxidant pretreatment consistently demonstrated a dual regulatory effect of enhancing or maintaining M1-like polarization while suppressing M2-like polarization. GS1R, GS1XR, and NAC were more effective overall than GS1, with GS1XR-featuring both membrane-penetrating and enzyme-responsive functionalities-showing particular promise as a radiotherapy adjuvant. This study reveals the bidirectional regulatory role of antioxidant treatment on macrophage polarization and provides a novel strategy for radiotherapy targeting macrophage plasticity. 放射治疗可重塑肿瘤微环境，既能促进肿瘤相关巨噬细胞向抗肿瘤表型(M1样)极化，也可诱导免疫抑制表型(M2样)促进肿瘤进展。为评估融合抗氧化酶GS1XR在放疗相关条件下对巨噬细胞极化的干预作用，本研究建立了过氧化氢(hydrogen peroxide, H2O2)对巨噬细胞RAW264.7的氧化应激模型，分析比较了GS1、GS1R和GS1XR对该细胞的细胞毒性、胞内ROS清除能力与细胞摄取能力，之后通过巨噬细胞M1样和M2样极化报告细胞(RAW-PNos2-P和RAW-PArg1-P细胞)检测了3种融合抗氧化酶与N-乙酰半胱氨酸(N-acetylcysteine, NAC)对H2O2、转化生长因子β1及受照鼻咽癌细胞的条件培养基诱导的巨噬细胞极化的干预效果。结果表明，200 μmol/L H2O2显著升高胞内活性氧(reactive oxygen species, ROS)，而对细胞活力影响较小;GS1R、GS1XR跨膜进入巨噬细胞的能力强于GS1，三者在使用剂量下均未显示明显毒性;不同抗氧化预处理在3种巨噬细胞极化诱导模型中均呈现出“增强/维持M1样、抑制M2样”的一致趋势，且GS1R、GS1XR与NAC效果整体优于GS1，其中兼具跨膜与酶切响应设计的GS1XR具备作为放疗辅助分子的应用前景。本研究揭示了抗氧化处理对巨噬细胞极化的双向调节作用，为靶向巨噬细胞极化的放疗辅助策略提供了新的思路与策略。.