Hydroformylation is a pivotal industrial homogeneous catalytic process, mainly relying on rhodium-based organophosphorus catalytic systems. However, this system faces critical challenges: cumbersome product separation, severe leaching of precious rhodium, and a low n/i (normal/iso-aldehyde) ratio of target products, hampering its industrial efficiency. Porous organic ligand polymers (POLs)—endowed with excellent thermal stability and hierarchical pores—are ideal heterogeneous supports for rhodium catalysts, effectively suppressing metal leaching and showing great potential in high-carbon olefin hydroformylation. Herein, we designed a xanthene-based oxygen-containing diphosphine ligand, which was copolymerized with vinyltriphenylphosphine to prepare porous organic copolymer supports with different monomer ratios. Using these supports, we successfully constructed a supported single-atom rhodium catalyst. Experimental results show that the catalyst exhibits excellent thermal stability and long-term durability, achieving high substrate conversion and remarkable n-aldehyde selectivity in the hydroformylation of high-carbon olefins (e.g., 1-octene). Characterization further reveals that the copolymerization-enabled precise regulation of the ligand microenvironment, combined with the xanthene-based diphosphine's modulation of the electronic state and spatial configuration of rhodium active centers, forms a synergistic effect—this is the key to the catalyst's significantly improved n/i ratio. This work addresses core limitations of traditional rhodium catalytic systems, offering a promising heterogeneous catalyst for efficient industrial hydroformylation of high-carbon olefins.

Locally delivering mesenchymal stem cells (MSCs) has been recently demonstrated to be successful in the treatment of intrauterine adhesions (IUA) by taking advantage of the immunomodulatory, pro-angiogenic, and anti-fibrotic properties of MSCs to facilitate endometrial regeneration and restore uterine function. However, direct exposure of these donor cells to the detrimental pathological microenvironment in the uterine cavity invariably leads to a low cell survival rate, poor control over cell fates, and impaired cellular functionalities, which can significantly compromise the therapeutic efficacy. Herein, we proposed a gelatin-based, colloid-assembled self-healing (CASH) hydrogel to deliver and retain the donor MSCs locally in the uterine cavity. The shear-thinning and self-healing behavior of CASH gel served as delivery vehicles to enable minimally invasive implantation and as extracellular matrix (ECM)-mimicking scaffolds to adapt locally to the complicated and pathological intrauterine environment. Importantly, CASH gel supports the adhesion and proliferation of MSCs in a 3D environment. We revealed that CASH gel enhances MSCs' paracrine activity through the PI3K signaling pathway, thereby reversing IUA and improving fertility via a four-pronged strategy involving immune remodeling, fibrosis deconstruction, vascular remodeling, and endometrial regeneration. Overall, this study has provided important insights into how it enhances the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for IUA.

Orthokeratology (OK) lenses for myopia correction are susceptible to biofouling by tear-derived biomolecules, escalating the risks of ocular infection and inflammation. Prevailing studies that rely on end point protein quantification fail to capture the real-time kinetics of fouling formation. Here, we fabricated a UV pressure-assisted polymer-grafted quartz crystal microbalance with dissipation monitoring (QCM-D) sensor exhibiting exceptional stability, nanoscale smoothness (RMS roughness ≈2 nm), and interfacial peel resistance. This platform enables in situ tracking of adsorption/desorption kinetics for four critical tear components: native/denatured lysozyme and oxidized/native lecithin. Key findings reveal a flow-dependent fouling behavior, wherein low flow rates increase biomolecule adsorption by 37-80% compared with higher flows. We further identify denatured lysozyme and native lecithin as resilient contaminants characterized by a stronger deposition affinity and pronounced resistance to elution. Quantitative screening of multipurpose solutions (MPSs) demonstrates that MPS #2 achieves 20-100% elution rate across biomolecules, outperforming commercial benchmarks. By leveraging dissipation-frequency (D-F) analysis, we clarify the fundamental mechanisms of biofouling formation at the molecular level. Collectively, this work establishes three critical advances: (1) a real-time biofouling diagnostic platform for OK lens interfaces, (2) molecular design principles for antifouling materials based on adhesion remodeling theory, and (3) an accelerated MPS formulation screening paradigm for ocular device safety.

Objective:Diabetic retinopathy (DR) is a primary contributor to vision loss worldwide and growing with an increase in the elderly population. Preventing or slowing DR progression remains a critical unmet need. Recognizing the significance of systemic and ocular chronic inflammation in the progression of DR, this study aimed to explore inflammatory factor profiles in plasma and tear samples to identify potential biomarkers and therapeutic targets. Methods:Using Olink's proximity extension assay, 92 inflammation-related proteins were measured in paired plasma and tear samples of 42 participants in type 2 diabetes mellitus (T2DM), DR and Diabetic Macular Edema (DME), followed by bioinformatic analysis for differentially expressed proteins (DEPs). Results:Different expression patterns of inflammatory proteins were observed between plasma and tear level. Plasma DEPs was mainly decreased during DR development, while tears DEPs mainly upregulated. DME had more differential cytokines than DR in both samples. By multi-comparison analyses, 23 inflammatory factors exhibited differential expression in the three compared groups (DR vs T2DM, DME vs T2DM and DME vs DR) in plasma level, and 30 differential inflammatory cytokines in tear samples. GO and KEGG analysis enriched pathways were primarily associated with extracellular region, cytokine activity, IL17 signaling pathway and JAK-STAT signaling pathway. Conclusion:Tears exhibit more DEPs than plasma during the progression of DR and DME, and the two sample types show opposite inflammatory factor expression trends. The DEPs in tears, especially the newly discovered inflammatory factors TNFSF14, CXCL11, IL6, CCL19, DNER and CXCL9 may serve as potential biomarkers for the diagnosis and progression monitoring of DR and DME.

The demand for corneal tissue healing and for the prevention of complications is growing. Conventional multi-drug eye drop therapy is significantly hampered by poor drug bioavailability and low patient compliance, which creates an urgent need for the development of drug co-delivery strategies. In this study, vitamin A palmitate (VAP) and prednisolone acetate (PA) were utilized to construct time-sequential drug-loaded bandage contact lenses (BCLs) to achieve the therapeutic requirements that address epithelial repair followed by stromal anti-inflammatory therapy. The solubility and drug-loading capacity of VAP and PA were enhanced by investigating cyclodextrin (CD) structures that encapsulate the two drugs. Subsequently, VAP pH-responsive films and PA sustained-release lenses were prepared separately and integrated into a "sandwich" structure. The fabricated dual-drug film BCLs achieved time-sequential delivery of VAP and PA over 144 h. In vitro release and permeation studies demonstrated the drug release behavior and release mechanisms of the film-based and BCLs-mediated drug delivery system. Comprehensive evaluations, including cytocompatibility assays, analysis of inflammatory cytokines, ocular irritation assessment, and alkali burn model studies, demonstrated the system's excellent biocompatibility, effective repair ability to promote corneal epithelial regeneration while significantly suppressing scar formation. This study not only achieved time-sequential drug release precisely tailored to the distinct healing requirements of different corneal injury stages but also elucidates the structure-release relationship of the BCLs system.

The enhancement of synthetic selectivity for immobilized Penicillin G acylase (PGA) is a key research objective in the industrial synthesis of antibiotics and the investigation of novel mechanisms against antibiotic-resistant bacteria. A hydrophilic microenvironment enhances the selectivity; however, the structure–function relationship and molecular mechanisms underlying the precise regulation of catalytic performance require urgent elucidation. In this study, we design and construct multiple zwitterionic multi-network alginate hydrogel systems for PGA immobilization. Using the synthesis of cephalexin as the model reaction, the catalytic activity, synthetic selectivity, and stability are evaluated. Compared to the free enzyme, the optimized zwitterionic immobilized enzyme system retains 84.9% relative activity and exhibit a 1.57-fold increase in selectivity. The influence of zwitterionic polymer on substrate adsorption capacity, affinity, and mass transfer efficiency during catalysis is systematically investigated, and the underlying molecular mechanisms are summarized. Furthermore, the hydrogel demonstrates excellent mechanical strength, printability, and resistance to enzyme aggregation. The 3D-printed hydrogel scaffolds show outstanding space-time yield, specific productivity, and long-term catalytic stability in continuous reactions. This work presents a robust immobilized enzyme carrier with high mass transfer efficiency and superior mechanical properties, and offers a novel strategy for developing high-performance, customizable biocatalytic systems.

The special structure of eyes and the existence of various physiological barriers make ocular drug delivery one of the most difficult problems in the pharmaceutical field. Considering the problems of patient compliance, local administration remains the preferred method of drug administration in the anterior part of eyes. However, local administration suffers from poor bioavailability, need for frequent administration, and systemic toxicity. Administration in the posterior part of the eye is more difficult, and intravitreal injection is often used. But intravitreal injection faces the problems of poor patient compliance and likely side effects after multiple injections. The development of nanocarrier technology provides an effective way to solve these problems. Among them, liposomes, as the most widely used carrier in clinical application, have the characteristics of amphiphilic nanostructure, easy surface modification, extended release time, good biocompatibility, etc. The liposomes are expected to overcome obstacles and effectively deliver drugs to the target site to improve ocular drug bioavailability. This review summarized the various controllable properties of liposomes for ocular delivery as well as the application and research progress of liposomes in various ocular diseases. In addition, we summarized the physiological barriers and routes of administration contained in eyes, as well as the prospects of liposomes in the treatment of ocular diseases.

The tumor microenvironment usually exhibits immunosuppressive characteristics, and pyroptosis is an effective method to stimulate antitumor immune responses. However, the current metal-ion-overload strategy to induce pyroptosis is hindered by the ion buffering system within the cell, which inhibits the release of exogenous ions. Herein, a biodegradable manganese-doped hydroxyapatite (Mn-HAP) with ultrasound (US) triggered continuous reactive oxygen species (ROS) modulation is proposed. Mn-HAP is defined as a sonoimmune stimulator because it functions as both a sonosensitizer and an immune agent. Before degradation, Mn-HAP exhibits an enhanced sonodynamic antitumor effect through the Mn-doping oxygen vacancies. Moreover, the built-in electric field induced by US activates the cell membrane-related ion channels and induces Ca2+ influx. Following the degradation of Mn-HAP in the slightly acidic tumor microenvironment, the released Ca2+ and ROS produced in sonodynamic therapy promote pyroptosis, while Mn2+ activates the cGAS-STING pathway, triggering innate immunity and further enhancing the effect of pyroptosis-induced immunotherapy. This work provides a promising strategy for engineering biodegradable materials for the sonodynamic immunotherapy of solid tumors.

Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

Carbodiimide reactions are widely employed for protein immobilization. Although coupling to primary amines is theoretically random, the charge on carbodiimide reactive intermediates can induce a preferential orientation of proteins during immobilization. The phenomenon of epitope bias has been observed during the screening of high-affinity antibodies using such immobilized proteins.

Immobilized enzyme packed bed reactors have contributed significantly to green and sustainable chemistry, yet design strategies at both molecular and system levels are needed. In this study, polylactic acid scaffolds were printed using 3D printing. The microporous scaffold with a high specific surface area was obtained through an etching-activation process. The enzyme sources and polymer microenvironments of site-specific immobilized His-tagged penicillin G acylase were screened. The polysulfobetaine methacrylate microenvironment displayed better relative activities, affinity, storage stability, and thermal and pH tolerance of enzyme compared to the PEG microenvironments. Packed bed reactors were constructed using scaffolds with different pore sizes, and the space-time yields were investigated. The internal flow behavior was studied using flow-field simulation and average residence time distribution. This study not only provides a robust multi-level design strategy for immobilized enzyme packed bed reactors but also presents new protocols for medical wastewater treatment and penicillin production.

PURPOSE. To characterize Zeb1 regulation of nitrogen mustard (NM)-induced acute corneal epithelial damage and its recovery in mice. METHODS. This study utilized topical fluorescein staining and section immunohistochemistry to evaluate NM-induced acute corneal epithelial damage and its recovery in both Zeb1 wild-type and heterozygous knockout mice, as well as real-time quantitative PCR and chromatin immunoprecipitation to delineate the mechanism underlying Zeb1 regulation of such corneal epithelial damage and recovery. RESULTS. Topical application of NM on the central cornea causes an immediate reduction of Zeb1 expression, followed by de-epithelization and epithelial cell death, along with cell proliferation resulting in epithelial recovery. Monoallelic knockout of Zeb1 decreased NM-induced acute epithelial damage but delayed the recovery from the damage. CONCLUSIONS. Zeb1 facilitates NM-induced corneal epithelial wound healing by maintaining epithelial renewability and thus is a potential therapeutic target to reduce acute mustard gas keratopathy in early ocular pathogenesis.

Corneal injury is a major cause of inflammation, scarring, and even vision loss. The main treatment for corneal injury is local administration of eye drops. However, due to the limitation of the protective barrier of the eyes, conventional eye drops have the disadvantages of low bioavailability, high side effects, and limited efficacy. In this study, the anti-inflammatory agent dipotassium glycyrrhizate (DG) and the antifibrotic agent ginsenoside Rg3 were incorporated into a thermosensitive hydrogel in order to develop a multifunctional hybrid hydrogel eye drops (RDTG) for the synergistic treatment of corneal alkali burn. The hydrogel network was formed by thiolated chitosan and β-glycerophosphate through both physical and chemical crosslinking. DG was distributed in free state in the hydrogel, while Rg3 was incorporated into the hydrogel in the form of liposomes. Furthermore, RDTG showed the characteristic of sequential drug-release. In vivo studies using a mouse model of corneal alkali burn have confirmed that RDTG could effectively reduce inflammation, promote corneal wound healing, and inhibit corneal scar. Therefore, the efficient delivery of RDTG eye drops provided a promising approach for the treatment of corneal alkali burn.

NaYF4:Er/Yb nanorods, colloidal crystal (CC) and Ag nanoparticles were obtained by solvothermal, self-assembly and hydrothermal methods, respectively. The hybrid structure of NaYF4:Er/Yb nanorods-colloidal crystal-Ag film (Ag-CC-NaYF4:Er/Yb) with low cost and large area was prepared for upconversion luminescence (UCL). The UCL enhancement was achieved by synergistic use of local reflection of incident light by colloidal crystal and reflection of incident light by Ag film. Compare with that of NaYF4:Er/Yb nanorods, the UCL intensity of Ag-CC-NaYF4:Er/Yb was increased by 33.2-folds. The UCL enhancement mechanism in Ag-CC-NaYF4:Er/Yb was investigated systematically. Our work has certain guiding value for promoting the application of upconversion nanocrystals in the fields of anti-counterfeiting, biological imaging, display and so on.

The control over enzyme immobilization and its microenvironment at the molecular level is deemed crucial. In this study, a "preblocking" method was performed through the use of natural polymer agarose resins after activation by phenyl-, methyl-, and ethyl-vinyl sulfones combined with divinyl sulfones prior to the specific immobilization of a his-tag fused recombinant nitrile hydratase (ReNHase). This technique primarily allows for the establishment of a hydrophobic microenvironment to enhance the immobilization and mass transfer and avoid inactivation caused by traditional backfilling. The purified ReNHase showed specific activity and regioselectivity of adiponitrile in an aqueous solution as 28.43 Umg-1 and 90.2%, respectively. Increasing the density of hydrophobic groups promotes the adsorption extent and immobilization yield of ReNHase. Optimized DVS:PVS 1:4 hydrophobic microenvironment could finish immobilization in 4h. Eminent expressed activity and regioselectivity of 94.6% and 93.9% was exhibited, respectively. The approach demonstrated exceptional selectivity in the biotransformation at the molecular level. Furthermore, the method was found to preserve enzymatic activity over seven cycles and exhibited significantly enhanced resilience to variations in the temperature and substrate concentration. The ReNHase@DVS:PVS 1:4 still retained 98% of the maximum activity, while ReNHase only retained 64% of activity at 55 degrees C. The ReNHase@DVS:PVS 1:4 still retained 55% of the maximum activity, while ReNHase was completely inactive at 200 mM adiponitrile. A packed-bed reactor was constructed, where the biotransformation of 5.64 g of 5-cyanovaleramide was carried out continuously for 48 h at a flow rate of 0.60 mL/min, achieving a peak space-time yield reported to be 0.93 molh(-1)L-1. The "preblocking" technique developed in this study is anticipated to provide new methodology in the catalysis of hydrophobic substrates.

为了制备高性能的改性沥青,以胺基修饰微纳米SiO2(粒径10 μm和20 nm)对基质沥青进行化学改性.首先,以偶氮二异丁腈为引发剂,使用马来酸酐对基质沥青进行化学改性制备活化沥青(MQL),再利用接枝了聚乙烯亚胺的 SiO2(PEI-SiO2)进行熔融共混改性得到改性沥青(PEI-SiO2-MQL).采用 FTIR、SEM 对PEI-SiO2-MQL 进行了表征,对其软化点、流变和老化性能进行了测试.结果表明,相比于纯 SiO2 物理改性沥青,PEI-SiO2 在沥青中分散性更佳.PEI-SiO2与沥青之间既有化学作用还有物理作用.PEI-SiO2-MQL的高温稳定性、抗车辙和抗老化性能均得到改善.

为改善医用材料的生物相容性并赋予材料表面一定的生物学功能,本文以单宁酸(TA)和聚醚胺ED900为组装单元,通过层层自组装的方法制备了复合涂层.采用纳米粒度仪、Zeta电位分析仪、紫外分光光度计、红外光谱、石英晶体微天平(QCM-D)、扫描电子显微镜等仪器对ED900-TA复合溶液行为及复合涂层的理化性质进行表征.通过细胞实验考察了涂层对细胞行为的影响.利用1,1-二苯基-2-三硝基苯肼(DPPH)法和总抗氧化能力检测试剂盒(FRAP)法评价了涂层的抗氧化性.最后,分别通过琼脂糖插入实验和细胞培养液浸泡研究涂层的稳定性.结果表明:ED900-TA涂层具有良好的细胞相容性和抗氧化性,表面的微结构呈现调控亲/憎细胞的能力.此外,涂层在模拟植入的过程未出现脱落.并在细胞培养条件下,涂层形貌在21天的评价周期内无显著变化.该复合涂层为生物材料表面多功能化提供了新思路.

Much effort in resource recycling and recovery has been devoted to developing durable materials for separation, but their versatility for emulsions and immiscible oil/water mixtures was far from ideal. In this work, a superhydrophobic sponge (MS-EP-APT) was developed using asphaltene (APT), melamine sponges (MS) and polyethyleneimine (PEI) for demulsification and water-oil mixture separation. These three easily obtained materials came from either oil refinement residue or low cost chemicals. The surface wettability, chemical stability, and mechanical durability of the sponge were analyzed to determine its separation potential. This sponge exhibited great separation efficiency for immiscible oil/water mixtures (> 96.0%), surfactant stabilized water-in-oil (W/O) emulsions (> 96.0%) and anionic surfactant-stabilized oil-in-water (O/W) emulsions (> 98.0%). It demonstrated good reusability and salt tolerance even in seawater. The separation mechanisms were proposed to be related to the hydrophobicity, positive charge, and torturous channels of the sponge. These superior performances make our sponge a strong candidate for green manufacturing and engineering in resource recovery and environmental remediation.

Injectable granular gels consisting of densely packed microgels serving as scaffolding biomaterial have re-cently shown great potential for applications in tissue regeneration, which allow administration via mini-mally invasive surgery, on-target cargo delivery, and high efficiency in nutrient/waste exchange. However, limitations such as insufficient mechanical strength, structural integrity, and uncontrollable differentiation of the encapsulated cells in the scaffolds hamper their further applications in the biomedical field. Herein, we developed a new class of granular gels via bottom-up assembly of cell-laden microgels via photo -triggered imine-crosslinking (PIC) chemistry based on the microfluidic technique. The particulate nature of the granular gels rendered them with shear-thinning and self-healing behavior, thereby functioning as an injectable and adaptable cellularized scaffold for bone tissue regeneration. Specifically, single cell -laden, monodisperse microgels composed of methacrylate-and o-nitrobenzene-functionalized hyaluronic acid and gelatin were prepared using a high-throughput microfluidic technique with a production rate up to 3.7 x 10 8 microgels/hr, wherein the PIC chemistry alleviated the oxygen inhibition on free-radical polymerization and facilitated enhanced fabrication accuracy, accelerated gelation rate, and improved net-work strength. Further in vitro and in vivo studies demonstrated that the microgels can serve as carriers to support the activity of the encapsulated mesenchymal stem cells; these cell-laden microgels can also be used as cellularized bone fillers to induce the regeneration of bone tissues as evidenced by the in vivo experiment using the rat femoral condyle defect model. In general, these results represent a significant step toward the precise fabrication of engineered tissue mimics with single-cell resolution and high cell -density and can potentially offer a powerful tool for the design and applications of a next generation of tissue engineering strategy.

Conventional manufacturing techniques to fabricate microfluidic chips, such as soft lithography and hot embossing process, have limitations that include difficulty in preparing multiple-layered structures, cost- and labor-consuming fabrication process, and low productivity. Digital light processing (DLP) technology has recently emerged as a cost-efficient microfabrication approach for the 3D printing of microfluidic chips; however, the fabrication resolution for microchannels is still limited to sub-100 microns at best. Here, we developed an innovative DLP printing strategy for high resolution and scalable microchannel fabrication by dosing- and zoning-controlled vat photopolymerization (DZC-VPP). Specifically, we proposed a modified mathematical model to precisely predict the accumulated UV irradiance for resin photopolymerization, thereby providing guidance for the fabrication of microchannels with enhanced resolution. By fine-tuning the printing parameters, including optical irradiance, exposure time, projection region, and step distance, we can precisely tailor the penetration irradiance stemming from the photopolymerization of the neighboring resin layers, thereby preventing channel blockage due to UV overexposure or compromised bonding stability owing to insufficient resin curing. Remarkably, this strategy can allow the preparation of microchannels with cross-sectional dimensions of 20 μm × 20 μm using a commercial printer with a pixel size of 10 μm × 10 μm; this is significantly higher resolution than previous reports. In addition, this method can enable the scalable and biocompatible fabrication of microfluidic drop-maker units that can be used for cell encapsulation. In general, the current DZC-VPP method can enable major advances in precise and scalable microchannel fabrication and represents a significant step forward for widespread applications of microfluidics-based techniques in biomedical fields.