Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers.

Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (Papp) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.

A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway.

OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.

Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy.

Monoclonal antibodies (mAbs) have become the predominant treatment modality for various diseases due to their high affinity and specificity. Although antibodies also have great potential for neurological diseases, they couldn't fully meet the therapeutic requirements due to their high molecular weight and limitations in crossing the blood-brain barrier (BBB). Herein, an innovative strategy based on exosomes (Exos) platform was developed to enhance the delivery of cetuximab (CTX) into the brain, and in combination with doxorubicin (DOX) for the synergistic targeted therapy of glioblastoma (GBM). The in vitro/vivo experiments have shown that exosomes could effectively promote BBB penetration and increase the content of CTX in glioma cells and brain lesions. Cytotoxicity and wound healing experiments have shown that CTX-Exo-DOX could significantly inhibit the proliferation of tumor cells. Finally, in vivo results showed that CTX-Exo-DOX significantly prolonged the survival time of tumor-bearing rats to 28 days, which was 1.47 times that of the DOX group. In summary, exosomes could deliver more antibodies into the brain, and CTX-Exo-DOX is a promising co-delivery system for the treatment of GBM. The results of this study will also provide a prospective strategy for antibody drugs in the treatment of neurological diseases.

Investigating the anti-atherosclerotic effects and potential mechanism of Dalbergia odorifera in ApoE-deficient mice using network pharmacology combined with metabolomics.

Dalbergia odorifera (DO) is a precious rosewood species in Southern Asia, and its heartwood is used in China as an official plant for invigorating blood circulation and eliminating stasis. This study aims to evaluate the efficacy of DO on atherosclerosis (AS), and further explore its active components and potential mechanisms. The apolipoprotein-E (ApoE)-deficient mice fed a high-fat diet were used as model animals, and the pathological changes in mice with or without DO treatment were compared to evaluate the pharmacodynamics of DO on AS. The mechanisms were preliminarily expounded by combining with metabolomics and network pharmacology. Moreover, the bioactive components and targets were assessed by cell experiments and molecular docking, respectively. Our findings suggested that DO significantly modulated blood lipid levels and alleviated intimal hyperplasia in atherosclerotic-lesioned mice, and the mechanisms may involve the regulation of 18 metabolites that changed during the progression of AS, thus affecting 3 major metabolic pathways and 3 major signaling pathways. Moreover, the interactions between 16 compounds with anti-proliferative effect and hub targets in the 3 signaling pathways were verified using molecular docking. Collectively, our findings preliminarily support the therapeutic effect of DO in atherosclerosis, meanwhile explore the active constituents and potential pharmacological mechanisms, which is conducive to its reasonable exploitation and utilization.

Homotypic targeted nanoplatform enable efficient chemoimmunotherapy and reduced DOX cardiotoxicity in chemoresistant cancer via TGF-ß1 blockade.

Doxorubicin (DOX) with broad-spectrum antitumor activity has been reported to induce effective immunogenic cell death (ICD) effect. However, the serious cardiotoxicity and chemoresistance severely restrict the widely clinical application of DOX. Herein, for the first time, a bio-inspired nanoplatform via co-assembly of DOX-conjugated polyethyleneimine (PEI-DOX), cancer cell membrane (CCM) and TGF-ß1 siRNA (siTGF-ß1) was rationally designed, which can not only overcome the drawbacks of DOX but also display high capability to modulate the tumor microenvironment and prevent the tumor progressing and metastasis. Experimental studies confirmed the pH-sensitivity of PEI-DOX and the homotypic-targeting and immuno-escapable ability of CCM, resulting an enhanced accumulation of DOX and siTGF-ß1 in tumor sites. In addition to this, the bio-inspired nanoplatform could also improve the stability and facilitate the endosomal escape of siTGF-ß1. All these effects ensured the silence efficiency of siTGF-ß1 in tumor sites, which could further modulate the chemoresistant and immunosuppressive tumor microenvironment, resulting a synergistic effect with DOX to prevent tumor progressing and metastasis. Additionally, even trapped in cardiac tissues, siTGF-ß1 could inhibit the production of TGF-ß1 and ROS induced by DOX, resulting a reduced myocardial damage. Therefore, our newly designed bio-inspired nano-delivery system may be a promising nanoplatform with efficient chemoimmunotherapy to ameliorate DOX-induced cardiotoxicity and combat tumor growth and metastasis in chemoresistant cancer.

Triptorelin nanoparticle-loaded microneedles for use in assisted reproductive technology.

Triptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased ß-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.

Effects of water-soluble additive on the release profile and pharmacodynamics of triptorelin loaded in PLGA microspheres.

A satisfactory drug release profile for gonadotropin-releasing hormone (GnRH) agonist drugs is high initial release followed by small amount of drug release per day. In the present study, three water-soluble additives (NaCl, CaCl2 and glucose) were selected to improve the drug release profile of a model GnRH agonist drug-triptorelin from PLGA microspheres. The pore manufacturing efficiency of the three additives was similar. The effects of three additives on drug release were evaluated. Under the optimal initial porosity, the initial release amount of microspheres containing different additives was comparable, this ensured a good inhibitory effect on testosterone secretion in the early stage. For NaCl or CaCl2 containing microspheres, the drug remaining in the microsphere depleted rapidly after the initial release. The testosterone concentration gradually returned to an uncontrolled level. However, for glucose containing microspheres, it was found that the addition of glucose could not only increase the initial release of the drug but also assist in the subsequent controlled drug release. A good and long-time inhibitory effect on testosterone secretion was observed in this formulation. The underlying cause why the incorporation of glucose delayed the subsequent drug release was investigated. SEM results showed that considerable pores in glucose containing microspheres were healed during the microspheres incubation. After thermal analysis, an obvious glass transition temperature (Tg) depression was observed in this formulation. As Tg decreased, polymer chains are able to rearrange at lower temperatures. This, morphologic change was reflected in the gradual closure of the pores, and is the likely reason that drug release slowed down after the initial release.HIGHLIGHTSThe addition of glucose could not only increase the burst release of the drug but also delay the subsequent drug release.High initial burst and a sustained drug release helped obtain a good inhibitory effect on testosterone secretion.As Tg decreased, polymer chain was prone to rearrange. Morphologic change was reflected in the gradual closure of the pores. This was the reason that drug release slowed down after the initial burst.

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity.

Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy.

Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.

Facile Solution-Refluxing Synthesis and Photocatalytic Dye Degradation of a Dynamic Covalent Organic Framework.

Covalent organic frameworks (COFs), as a novel crystalline porous adsorbent, have been attracting significant attention for their synthesis and application exploration due to the advantages of designability, stability, and functionalization. Herein, through increasing the concentration of the acid catalyst, a facile solution-refluxing synthesis method was developed for the preparation of a three-dimensional dynamic COF material, COF-300, with high yields (>90%) and high space−time yields (>28 kg m−3 day−1). This synthesis method not only permits gram-scale synthesis, but also yields products that well maintain porosity and unique guest-dependent dynamic behavior. Moreover, the catalytic activity of COF-300 as a metal-free photocatalyst was explored for the first time. Under 365 nm ultra-violet light irradiation, COF-300 can effectively catalyze the dye degradation (>99%) in wastewater with good recyclability. By adding magnetic Fe3O4 nanoparticles into the solution-refluxing synthesis of COF-300, Fe3O4/COF-300 nanocomposites can be obtained and used as magnetically recyclable photocatalysts, demonstrating the superiority of this facile synthesis procedure. Our study provides new insights for the preparation of COF materials and a constructive exploration for their water treatment application.

Attitude and influencing factors of patients with schizophrenia toward long-acting injections: A community-based cross-sectional investigation in China.

Background: Low prescription rates of antipsychotic long-acting injections (LAIs) may be a major challenge in the prevention and treatment of schizophrenia. However, there are few studies on the usage and attitude toward LAIs among community-based patients with schizophrenia. Methods: A large community-based cross-sectional investigation was conducted among 6,336 patients with schizophrenia from Shanghai, China from March 1 to June 30, 2021. The structured Attitude and Status toward Treatment of Community Patients with Schizophrenia Questionnaire (AST-CSQ) was used to investigate the attitude and influencing factors of community-dwelling patients with schizophrenia toward LAIs. Results: Among the 6,336 participants, the average age was 49.28 ± 11.23. The rate of agreement to LAI antipsychotics among participants was 3.16% (n = 200). The family financial resources, care ability, and disease course of the LAIs group were less than those of the non-LAIs group. However, the LAIs group had higher immediate family guardianship, social activity, previous hospitalization, number of hospitalization, outpatient adherence, previous antipsychotic use, antipsychotic adherence, and attitude toward oral antipsychotics than the non-LAIs group, with significant differences between the two groups (p < 0.05). Furthermore, age (ß = -0.036, OR 0.964, 95% CI 0.947-0.982), marital status (ß = 0.237, OR 1.267, 95% CI 1.002-1.602), care ability (ß = 0.709, OR 2.032, 95% CI 1.437-2.875), outpatient adherence (ß = -0.674, OR 0.510, 95% CI 0.358-0.725), antipsychotic adherence (ß = 0.920, OR 2.509, 95% CI 1.092-5.764), and attitude toward oral antipsychotics (ß = -1.357, OR 0.258, 95% CI 0.103-0.646) were significant predictors of attitude toward LAI antipsychotics (p < 0.05). Conclusions: The community-dwelling patients with schizophrenia in China had a low willingness to use LAIs. Patients of a younger age, more hospitalizations, and a shorter course of disease were prone to be more willing to accept LAIs. The patients' age, marital status, care ability, outpatient adherence, antipsychotic adherence, and attitude toward oral antipsychotics were important predictor of patients' attitudes toward LAIs. Under the global deinstitutionalized management model of mental disorders, these results highlight an urgent problems for public mental health service providers and policy-makers and provide more solutions for them.

Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis.

Background: To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Methods: Systematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I2 statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg's and Egger's tests. Results: This meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias. Conclusions: Women with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776).

Tanshinone IIA-Loaded Micelles Functionalized with Rosmarinic Acid: A Novel Synergistic Anti-Inflammatory Strategy for Treatment of Atherosclerosis.

Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis.

Hyaluronic acid-modified redox-sensitive hybrid nanocomplex loading with siRNA for non-small-cell lung carcinoma therapy.

A novel hyaluronic acid (HA)-modified hybrid nanocomplex HA-SeSe-COOH/siR-93C@PAMAM, which could efficiently deliver siRNA into tumor cells via a redox-mediated intracellular disassembly, was constructed for enhanced antitumor efficacy. Thereinto, siR-93C (siRNA) and positive PAMAM were firstly mixed into the electrostatic nano-intermediate, and then diselenide bond (-SeSe-)-modified HA was coved to shield excessive positive charges. This hybrid nanocomplex displayed uniform dynamic sizes, high stability, controlled zeta potential and narrow PDI distribution. Moreover, the -SeSe- linkage displayed GSH/ROS dual responsive properties, improving intracellular trafficking of siRNA. In vitro assays in A549 cell line presented that HA-SeSe-COOH/siR-93C@PAMAM has low cytotoxicity, rapid lysosomal escape and significant transfection efficiency; besides, an efficient proliferation inhibition ability and enhanced apoptosis. Furthermore, in animal studies, this negative-surfaced hybrid nanocomplex showed a prolonged circulation in blood and improved inhibition of tumor growth. All these results verified our hypothesis in this study that diselenide bonds-modified HA could promote not only stability and safety of nanoparticles in vivo but also intracellular behavior of siRNA via redox-dual sensitive properties; furthermore, this hybrid nanocomplex provided a visible potential approach for siRNA delivery in the antitumor field.

Thylakoid Membrane-Inspired Capsules with Fortified Cofactor Shuttling for Enzyme-Photocoupled Catalysis.

Enzyme-photocoupled catalytic systems (EPCSs), combining the natural enzyme with a library of semiconductor photocatalysts, may break the constraint of natural evolution, realizing sustainable solar-to-chemical conversion and non-natural reactivity of the enzyme. The overall efficiency of EPCSs strongly relies on the shuttling of energy-carrying molecules, e.g., NAD+/NADH cofactor, between active centers of enzyme and photocatalyst. However, few efforts have been devoted to NAD+/NADH shuttling. Herein, we propose a strategy of constructing a thylakoid membrane-inspired capsule (TMC) with fortified and tunable NAD+/NADH shuttling to boost the enzyme-photocoupled catalytic process. The apparent shuttling number (ASN) of NAD+/NADH for TMC could reach 17.1, ∼8 times as high as that of non-integrated EPCS. Accordingly, our TMC exhibits a turnover frequency (TOF) of 38 000 ± 365 h-1 with a solar-to-chemical efficiency (STC) of 0.69 ± 0.12%, ∼6 times higher than that of non-integrated EPCS.

General framework for enzyme-photo-coupled catalytic system toward carbon dioxide conversion.

High emission of carbon dioxide (CO2) has aroused global concern due to the 'greenhouse effect'. The conversion of CO2 to valuable chemicals/materials is an indispensable route toward 'carbon neutrality'. Enzyme-photo-coupled catalytic systems (EPCCSs), integrating synthetic library of semiconductor photocatalyst and natural database of enzyme, have emerged as a green and powerful platform toward CO2 conversion. Herein, we discuss the recent progress in design and application of EPCCSs for CO2 conversion from the perspective of pathway engineering, reaction engineering and system engineering. We firstly summarize the explored pathways of EPCCSs for converting CO2 to C1 and C2+ products. Secondly, we discuss the matching of kinetics between photocatalytic and enzymatic reactions in EPCCSs. Thirdly, we unveil the complex interplay between photocatalytic and enzymatic modules, and further demonstrate the strategy of compartmentalization to eliminate the negative interactions. Lastly, we conclude with the perspective on the opportunities and challenges of EPCCSs for CO2 conversion.

Silk fibroin double-layer microneedles for the encapsulation and controlled release of triptorelin.

A double-layer silk fibroin microneedles (SF-MNs) was proposed for the transdermal delivery of triptorelin. Two-step pouring and centrifugation were employed to prepare SF-MNs. Triptorelin was wrapped in MNs in the form of microcrystals with a size of ∼1 µm. ß-sheet nanocrystals (the secondary structure of silk fibroin) were adjusted in content by methanol-vapor treatment to manipulate the characteristics of SF-MNs prepared with two concentrations of silk fibroin. The mechanical strength of MNs was measured and analyzed in proportion to the ß-sheet content. The triptorelin in MNs could be released sustainedly in phosphate-buffered saline for 168 h, and the release amount decreased with increasing ß-sheet content. The Ritger-Peppas equation was employed to fit the release data. A linear decreasing relationship was observed between the diffusion coefficient and increased ß-sheet content. After administration to rats, SF-MNs exhibited long-term testosterone inhibition and maintained castration levels for ≥7 d. Manipulable mechanical properties and release behavior combined with biocompatibility and biodegradability render SF-MNs as viable long-term transdermal delivery devices for triptorelin.

Enzyme-photo-coupled catalytic systems.

Efficient chemical transformation in a green, low-carbon way is crucial for the sustainable development of modern society. Enzyme-photo-coupled catalytic systems (EPCS) that integrate the exceptional selectivity of enzyme catalysis and the unique reactivity of photocatalysis hold great promise in solar-driven 'molecular editing'. However, the involvement of multiple components and catalytic processes challenged the design of efficient and stable EPCS. To show a clear picture of the complex catalytic system, in this review, we analyze EPCS from the perspective of system engineering. First, we disintegrate the complex system into four elementary components, and reorganize these components into biocatalytic and photocatalytic ensembles (BE and PE). By resolving current accessible systems, we identify that connectivity and compatibility between BE and PE are two crucial factors that govern the performance of EPCS. Then, we discuss the origin of undesirable connectivity and low compatibility, and deduce the possible solutions. Based on these understandings, we propose the designing principles of EPCS. Lastly, we provide a future perspective of EPCS.