Peptic ulcer disease (PUD), a common gastrointestinal disorder mainly treated with oral drug formulations, faces formidable therapeutic challenges, including poor drug targeting and superficial treatment. To address these limitations, a trajectory-modulating endoscope-actuated microneedle-based “bullet” (TEMB) was proposed and developed, which integrated expansible/penetrative microneedles, a shape-alterable multilayered protector, and a rifling-based trajectory-modulating sleeve, enabling deep drug delivery and precise targeting to ulcerative lesions. Notably, evaluations conducted in porcine stomachs and in an actual pathological ulcer model demonstrated the significant advantages of the TEMB system in localization accuracy, drug penetration, and formulation stability, effectively overcoming the limitations of conventional oral and liquid-based therapies. Collectively, the results of this study present a promising platform for PUD treatment, proposing an encouraging conceptual framework for the design of endoscopically interventional systems adapted to the complexities of the gastrointestinal environment.

Bacterial keratitis poses a significant global challenge due to rapid progression, antibiotic resistance, and corneal drug delivery difficulties. Facing the problems, we designed a mantis-forelimb-inspired bioabsorbable lens-like ocular therapeutic (BLOT) device with an oriented microneedle for treating bacterial keratitis. Microneedles arranged on the outer ring possess varying tilted angles, facilitating minimally invasive delivery of therapeutics to deeper corneal layers while reducing tissue damage. Additionally, sericin microspheres were engineered for in situ reduction of silver nanoparticles, which were then integrated in the oriented microneedles, demonstrating highly efficient antibacterial properties after penetrating the corneal epithelial layer. Notably, treatment with local BLOT produced a significantly thinner cornea (643.5 ± 5.3 μm) than levofloxacin eye drops (920.7 ± 5.7 μm) in a rabbit model of bacterial keratitis, demonstrating nearly 30% reduction in thickness. As a minimally invasive ocular drug delivery system, the BLOT device facilitates efficient and rapid corneal healing, offering a novel solution for bacterial keratitis treatment.

Dexmedetomidine, known as an exceptionally potent and highly selective α2-adrenergic receptor agonist, is widely used as a safe and effective intravenous sedative agent in both surgical and nonsurgical settings. As the need for an optimized sedative delivery system grows—one that is not only easy to apply but also demonstrates superior efficacy, particularly among pediatric patients and other groups with lower levels of cooperation—innovative delivery methods are increasingly sought. To address this need, we developed a caramelized amorphous sucrose-based lunging microneedle array (CALM), incorporating an advanced Kelvin cell lattice framework. This lattice improves the microneedle array’s surface contact with tissues, accelerating and enhancing the drug release process. Additionally, unlike conventional sucrose-based microneedles, which often crystallize and lose mechanical strength, the caramelization process reduces crystallinity, increasing both the stability and structural integrity of the system. These combined features make CALM a highly effective and patient-friendly option for administering dexmedetomidine. Preliminary trials in clinical simulations showed a rapid onset of sedation with minimal discomfort, highlighting its potential as a promising solution for vulnerable populations needing fast and secure sedation.

Probiotic-based biotherapy for colorectal cancer (CRC) faces significant challenges due to poor tumor-targeting and limited bioactivities within the complex tumor microenvironment. This study shows that Lactobacillus reuteri (L. reuteri)'s inherent bioactivities, including proliferation, metabolism, and colorectal colonization, can be enhanced by manganese, prompting the fabrication of a manganese-engineered strain (MnLR). Oral administration of MnLR with its metabolic substrate-glycerol (MnLR/Gly) promotes the enrichment of L. reuteri and its antitumor metabolites within colon tumors. Across multiple preclinical colon tumor models, MnLR/Gly alone achieves a 95.6% inhibition of orthotopic tumor growth, liver metastases reduction by 62.1%, and confers durable protection, with 75% of prophylactically treated mice remaining long-term tumor-free and 62.5% resisting tumor rechallenge. Mechanistically, MnLR/Gly induces both intratumoral and peripheral dendritic cell maturation, M1 macrophage polarization, and effector T-cell responses. In orthotopic CRC rabbit models, GlyMnLR enteric capsules demonstrate significant antitumor efficacy comparable to standard chemotherapy while exhibiting favorable safety. These findings highlight MnLR as an effective standalone probiotic therapy for CRC prevention and treatment.

Despite the nascent stage of research into protocells and prototissues, their substantial potential has increasingly positioned them as a focal point in recent years. The bottom-up reconstruction of life systems is gradually garnering widespread attention. In this study, a type of protocells and corresponding prototissues based on polyphenol coacervate droplets were developed via hydrogen bond interactions. The droplets exhibited properties reminiscent of cytoplasm, enriching a wide range of substances. Upon further modification with lipid bilayers, the protocells not only achieved a structural resemblance to natural cells, but also effectively maintained the stability. Prototissues formed by the orderly aggregation of protocells can not only encapsulate living cells, but also maintain the structural integrity and function of both artificial and living cells. At the macroscopic level, the prototissues were injectable, customizable in shape, bioadhesive, and capable of long-term retention in vivo. Moreover, the prototissues showed no obvious inflammatory responses. Polyphenol-based protocells and tissues with unique characteristics may offer new insights for research and applications in organoids, transplantation, and medical devices.

Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Conventional drug delivery methods for chronic disease often suffer from low potency and poor patient compliance, while current advanced devices face limitations because of bulkiness, frequent implantation needs, inflammation risk, and lack of precise control. To overcome these challenges, we developed the SUSTAIN-a smart, ultra-long-lasting, sequentially triggerable, and artfully implantable nozzle system. The SUSTAIN integrates an osmotic pressure-triggered module, an airflow-generated T-pipe (AGT), and a drug infusion pump (DIP) for controlled subcutaneous drug release. The AGT enables tunable dosing by varying NaHCO3/KH2PO4 powder amounts, while shear thinning of the β-cyclodextrin/Pluronic F-127 hydrogel in the DIP ensures sustained drug infusion. In vivo studies show that the SUSTAIN delivers at least four doses of levothyroxine sodium over 10 days and three doses of semaglutide over 42 days, maintaining effective blood drug levels with minimal invasiveness. This system presents a highly promising solution for improving therapeutic outcomes and convenience in chronic disease management.

Cancer therapy based on extracellular vesicles faces several practical challenges, such as low production, inadequate stability, and inefficiency, making it difficult to achieve ideal therapeutic effects. To address these issues, a novel engineering technology of EVs was developed based on the autonomous "fusion-exocytosis" process. Specifically, membrane fusogenic liposomes (MFLs) with unique physical and chemical properties were engineered by tailoring the components, which could interact with cells to facilitate mutual fusion of lipid membranes and release fusogenic extracellular vesicles (FEVs). As an inducer of immunogenic cell death (ICD) and enhancer of EV production, monensin (Mon) was incorporated into MFLs. The synergistic action of MFLs and Mon not only increased the production of released FEVs but also significantly enhanced their immunogenicity, effectively promoting maturation of dendritic cells (DCs). Consequently, the obtained FEVs effectively inhibited tumor growth by activating anti-cancer immune responses. This engineering method of generating FEVs could substantially increase production and enhance immunogenicity, which would facilitate their clinical translation for cancer therapy.

BACKGROUND AND OBJECTIVE:Classical mycosis fungoides (CMF), the most common form of primary cutaneous T-cell lymphoma, shows marked heterogeneity in disease progression and prognosis, while reliable molecular prognostic markers remain scarce. This study aimed to evaluate the prognostic significance of GATA-binding protein 3 (GATA3) expression in early-stage CMF. METHODS:We retrospectively analyzed 106 patients with early-stage CMF diagnosed at West China Hospital, Sichuan University, between 2009 and 2021. Immunohistochemistry (IHC) was performed to assess GATA3 expression in dermal tumor cells. Associations with progression-free survival (PFS) and overall survival (OS) were examined using Cox regression models adjusted by inverse probability of treatment weighting (IPTW). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate predictive performance. RESULTS:High GATA3 expression (≥ 60%) was detected in 92.5% of cases. Elevated GATA3 levels were significantly associated with reduced PFS and OS. IPTW-adjusted Cox regression confirmed high GATA3 expression as an independent adverse prognostic factor. ROC curve analysis demonstrated strong predictive performance for CMF progression (AUC = 0.867), with an optimal cutoff of 57.5% (sensitivity 73.7%, specificity 94.3%). For clinical applicability, a 60% threshold was adopted. CONCLUSION:High GATA3 expression is an independent adverse prognostic biomarker in early-stage CMF. Incorporating GATA3 into risk stratification models may improve prognostic accuracy and guide personalized treatment strategies.

Cancer diagnosis and treatment remains challenging, with unresolved issues such as low targeting, drug resistance, and numerous adverse reactions from chemotherapy. Cell membrane biomimetic modified nanoparticles(CMBMNPs), wrapping cell membrane on nanoparticles can achieve homologous cell mimicry, so that it can obtain the functions and properties of the type of cell, with strong targeting ability, strong immune evasion ability, long in vivo circulation time, etc., which is getting more and more attention. This article describes the preparation process of CMBMNPs and the different clinical effects of different types of nanoparticles and mimicking cell membranes in order to select the right match for use. In addition, we list in detail several important features of CMBMNPs as well as the advantages of CMBMNPs in areas related to cancer diagnosis and therapy, and look forward to the future challenges and prospects of cell membrane-generating nanotechnology, which provides new insights into the application of CMBMNPs in cancer diagnosis and therapy.

Hypoxia serves as a critical determinant in the advancement of various intractable pathological conditions including oncological disorders and hypovascular wounds, which may profoundly attenuate the efficacy of pharmacological interventions and substantially inhibit the physiological recovery processes. Consequently, in an effort to mitigate the inherent constraints of conventional methodologies (e.g., exogenous oxygen delivery systems), a self-powered triboelectric nanogenerator (TENG)-based algae-integrated pliable and enveloped device (TAPED) operates as a wearable system to sustain oxygen generation. The TAPED system harnesses biomechanical energy generated through natural bodily movements to energize an integrated luminescent source, enabling controlled photosynthesis for sustained, on-demand oxygen production. The incorporation of TENG technology renders TAPED self-sufficient, eliminating the necessity for external recharging, reducing device mass, and improving convenience for continuous oxygen delivery. Additionally, its body-attachable design circumvents risks associated with direct algal implantation, such as immunogenic reactions and infections. Specifically, experimental application of TAPED has exhibited significant therapeutic efficacy in diverse pathological conditions, including diabetic chronic infected wounds, breast carcinoma tumors, and lactic acid accumulation consequent to strenuous exercise-induced fatigue. Collectively, the TAPED represents an advanced therapeutic approach, which holds substantial potential for translational application within clinical contexts, particularly for enhancing patient prognosis in hypoxic diseases such as oncology and wound management.

Chemotherapeutic drugs have low aggregation rates and short retention times in tumors, severely limiting their clinical application. Additionally, the development and spread of solid tumors is highly dependent on neovascularization. An RGD-modified acid-responsive peptide was designed to encapsulate the chemotherapeutic drug paclitaxel (PTX) and the antiangiogenic drug sorafenib (SF), enabling them to self-assemble into nanoparticles (NPs) in a physiological environment. In an acidic environment, the release of PTX and SF was achieved when the drug-loaded experimental peptide PS/Pep1 transformed from spherical NPs into aggregates containing nanofibers, which effectively prolonged the retention of the encapsulated drug and increased drug accumulation. Furthermore, in vivo experiments provided compelling evidence of the strong inhibitory effects of PS/Pep1 on tumor growth and metastasis, as well as its effective suppression of angiogenesis. This targeted NP system that undergoes a morphological shift in the tumor microenvironment holds promise for enhancing the efficacy of the combined administration of chemotherapeutic and antiangiogenic drugs to inhibit tumor growth and metastasis.

This is an application of an improved remote infusion catheter in femoral artery veno-arterial extracorporeal membrane oxygenation (VA ECMO). VA ECMO is a critical technique for treating cardiogenic shock and cardiac arrest. However, acute limb ischemia has emerged as a severe complication of this treatment method, potentially significantly impacting patient prognosis and survival rates. We propose a modified remote infusion catheter method that utilizes a double male luer-lock connector to directly connect to the arterial sheath. This aims to address certain issues present in current methods, such as the absence of matching tubing in the kit.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24 weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Anastomotic leakage (AL) is a pervasive and risky postoperative complication that presently features inaccessible prevention, delayed diagnosis, and intractable remediation, resulting in distressing morbidity and mortality. Herein an interior/exterior collaboration-enhanced neoteric intestinal anastomosis (IECIA) is developed, which consists of an interior hydrogel-based protective barrier adhering to mucosa, and exterior synergistic leakage-prevention safeguard sutured to serosa, for multi-tiered leakage complication management. Noticeably, the hydrogel barrier protects anastomosis stoma against injurious stimulation from digestive liquid, consequently reducing leakage risk effectively and comfortably in place of painful gastric tube insertion. The exterior safeguard encompassing fluorescein-loaded hydrogel and electrospun film functions as a secondary defense, exhibiting critical leakage-prevention capability to refrain from lethal intra-abdominal infection. Meanwhile, fluorescein is released to the enteric cavity for following detection within the excrement in case anastomotic leakage occurs, achieving presymptomatic alarming in providing valuable prompts for timely clinical intervention. Importantly, IECIA has been investigated in realistic in vivo end-to-end intestinal anastomosis scenarios as well as simulated leakage models, which present satisfactory postoperative recovery of gastrointestinal functions and systematic indexes. Moreover, the IECIA system is endowed with guaranteed biocompatibility, effective durability, comprehensibility for surgical operation, comfort, and compliance for patients, which demonstrates precious value for clinical translation.

Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of H2O2. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.

The reasons for the high recurrence and metastasis after triple-negative breast cancer (TNBC) surgery are the potential presence of micrometastases and disseminated tumor cells in the circulation, as well as the immunosuppressive microenvironment caused by the surgery. To address these issues, this work proposed a platelets (PLTs) based hydrogel delivery system for immuno-chemotherapy, (IL-12+NPD-PLT)@dAlg. To utilize the targeting ability of PLTs toward tumor cells and maintain the activity of PLTs, doxorubicin-loaded nanoparticles (NPD) were attached on the surface of PTLs (NPD-PLT). Under the conditions of the post-surgical tumor microenvironment (TME), these PTLs responsively released small-sized drug-loaded vesicles (NPD-PMP) trapping metastatic tumor cells, inducing immunogenic cell death (ICD) of tumor cells. Additionally, immunomodulatory drugs, IL-12, was combined in the hydrogel to synergistically activate CD8+ T cells within the body and induce the polarization of tumor-associated macrophages (TAMs) toward M1 cells, thereby improving the immunosuppressive microenvironment post-surgery. In a 4T1 tumor recurrence and metastasis mouse model, (IL-12+NPD-PLT)@dAlg has shown effective inhibition of tumor recurrence and metastasis, reversing the tumor immune environment, and prolonging survival.

The β-type anti-Id (Ab2β) is considered to have potential for simulating the structure and function of the antigen. In this study, a β-type anti-Id (3A7 anti-I-GEAb) of the Cry1C toxin was captured from a GEAb library. Subsequently, a higher activity of mutant (3A7 mutant 8) was obtained from the mutagenesis library based on 3A7 anti-I-GEAb. The LD50 values of 3A7 anti-I-GEAb and 3A7 mutant 8 reach up to 38.9% and 46.8% of Cry1C toxin for P. xylostella and reach up to 32.9% and 37.4% of Cry1C toxin for H. armigera. Additionally, an IC-ELISA was established based on 3A7 mutant 8 (as the coated "antigen"), with an LOD value of 0.35 ng/mL, exhibiting good accuracy and stability for detecting Cry1C toxin in spiked samples. The present β-type anti-I-GEAb not only exhibits insecticidal activity similar to Cry1C toxin, offering potential for environmentally friendly pest management, but it can also replace the Cry1C toxin structure to establish a highly sensitive and specific IC-ELISA for monitoring Cry1C toxin.