Glucose Oxidase-Immobilized Dually-Crosslinked Nanogels for Rapid-Responsive Insulin Delivery.

Despite the potential benefits of close-looped insulin delivery systems in regulating glycemic homeostasis and effectively alleviating diabetes, they still encounter challenges such as limited effectiveness in preventing low glycemic episodes due to sluggish glucose response, and issues with the instability of enzymes and carriers. In this study, dually-crosslinked and glucose oxidase (GOx)-immobilized insulin nanogels (DC-NGs@Ins) are developed for rapid-responsive and sustained hypoglycemic therapy. The DC-NGs@Ins with the phenylborate ester linker enabled the insulin release in a close-looped fashion, and moreover, immobilized GOx-generated hydrogen peroxide (HO) by consuming the glucose, which can further bind to phenylborate ester for enhancing glucose response and accelerating the insulin release.

Bioresponsive Nanoparticles Boost Starvation Therapy and Prevent Premetastatic Niche Formation for Pulmonary Metastasis Treatment.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition.

Photothermal-controlled NO-releasing Nanogels reverse epithelial-mesenchymal transition and restore immune surveillance against cancer metastasis.

Metastasis leads to high mortality among cancer patients. It is a complex, multi-step biological process that involves the dissemination of cancer cells from the primary tumor and their systemic spread throughout the body, primarily through the epithelial-mesenchymal transition (EMT) program and immune evasion mechanisms. It presents a challenge in how to comprehensively treat metastatic cancer cells throughout the entire stage of the metastatic cascade using a simple system.

ROS-responsive core-shell nano-inhibitor impedes pyruvate metabolism for reinforced photodynamic therapy and interrupted pre-metastatic niche formation.

The formation of pre-metastatic niche (PMN) in a hospitable organ derived from the primary tumor requires the communication between the tumor cells and the host environment. Pyruvate is a fundamental nutrient by which the tumor cells metabolically reshape the extracellular matrix in the lung to facilitate their own metastatic development. Here we report a combination regimen by integrating the photo-sensitizer and the mitochondrial pyruvate carrier (MPC) inhibitor in a dendritic polycarbonate core-hyaluronic acid shell nano-platform with multivalent reversible crosslinker embedded in it (DOH-NI+L) to reinforce photodynamic therapy (PDT) toward the primary tumor and interrupt PMN formation in the lung via impeding pyruvate uptake.

Recent developments in the fabrication of food microparticles and nanoparticles using microfluidic systems.

Microfluidics is revolutionizing the production of microparticles and nanoparticles, offering precise control over dimensions and internal structure. This technology facilitates the creation of colloidal delivery systems capable of encapsulating and releasing nutraceuticals. Nutraceuticals, often derived from food-grade ingredients, can be used for developing functional foods.

Design and performance analysis of a new inferior vena cava filter.

This study proposes a novel inferior vena cava filter (IVCF) design, "Lotus," aiming to enhance release stability and endothelialization. A catheter-filter-vessel model was established for IVCF property analysis, validated by comparing numerical simulations and in vitro tests. Lotus's mechanical properties were analyzed, and optimization suggestions are provided.

Ursodeoxycholic Acid-Decorated Zwitterionic Nanoparticles for Orally Liver-Targeted Close-Looped Insulin Delivery.

Oral insulin therapies targeting the liver and further simulating close-looped secretion face significant challenges due to multiple trans-epithelial barriers. Herein, ursodeoxycholic acid (UDCA)-decorated zwitterionic nanoparticles (NPs) (UC-CMs@ins) are designed to overcome these barriers, target the liver, and respond to glycemia, thereby achieving oral one-time-per-day therapy. UC-CMs@ins show excellent mucus permeability through the introduction of zwitterion (carboxy betaine, CB).

PVA-based bulk microneedles capable of high insulin loading and pH-triggered degradation for multi-responsive and sustained hypoglycemic therapy.

"Closed-loop" insulin-loaded microneedle patche shows great promise for improving therapeutic outcomes and life quality for diabetes patients. However, it is typically hampered by limited insulin loading capacity, random degradation, and intricate preparation procedures for the independence of the "closed-loop" bulk microneedles. In this study, we combined the solubility of microneedles and "closed-loop" systems and designed poly(vinyl alcohol)-based bulk microneedles (MNs@GI) through photopolymerization for multi-responsive and sustained hypoglycemic therapy, which significantly simplified the preparation process and improved insulin loading.

Super-small zwitterionic micelles enable the improvement of blood-brain barrier crossing for efficient orthotopic glioblastoma combinational therapy.

Glioblastoma multiforme (GBM) remains incurable in clinical, nanotechnology-based drug delivery strategies show promising perspective in alleviating GBM, while limited blood-brain-barrier (BBB) permeation, short blood half-live accompanied by the poor tumor accumulation and penetration, significantly restrict the therapeutic outcomes. Herein, a versatile super-small zwitterionic nano-system (M(S)) based on carboxybetaine (CB) zwitterion functionalized hyperbranched polycarbonate (HP) is developed to overcome the brain delivery challenges. After grafting with amino-functionalized IR780 (free IR780), the ultimate paclitaxel (PTX)-encapsulated micelles (M(S)-IR@PTX) are precisely activated by near-infrared (NIR) for accelerated drug release and effective combinational GBM therapy.

Two-in-One Polymeric NO-Donor Prodrugs Mediate Precision and Synergistic Prostate Cancer Treatment.

Chemotherapy predominates in clinical treatment of prostate cancer (PCa), while irreversible resistance to chemotherapeutics and severe side effects hinder the therapeutic efficacy, especially in castration-resistant PCa (CRPC). Herein, a bombesin (BBN)-decorated two-in-one prodrug (T-NO/E-PMs) incorporating a polymeric nitric oxide (NO) donor and acetal-linked 17β-estradiol (E) in one backbone is developed, aiming to inhibit androgen receptor (AR) expression, reprogram the tumor microenvironment of CRPC, and enhance estradiol-mediated hypoxic CRPC therapy. Following efficient internalization mediated by BBN, T-NO/E-PMs releases estradiol and NO in response to the unique intracellular environments.

[Effect of early fluid balance on the prognosis in severe acute pancreatitis].

Objective: To observe the correlation between early fluid resuscitation and prognosis in patients with severe acute pancreatitis (SAP).

Methods: SAP patients admitted to the department of critical care medicine of the People's Hospital of Chuxiong Yi Autonomous Prefecture of Yunnan Province from June 2018 to December 2020 were enrolled and analyzed retrospectively. All patients were given the routine treatment according to their condition and relevant diagnostic According to their different prognosis, enrolled patients were divided into death group and survival group.

A glucose-responsive nitric oxide release hydrogel for infected diabetic wounds treatment.

Bacteria-infected chronic wound is one of the most serious complications of diabetes and characterized with high morbidity and risk of lower extremity amputation. Nitric oxide (NO) represents a promising strategy to accelerate wound healing through down-regulating inflammation, promoting angiogenesis and bacterial eradication. However, stimuli-responsive and control release of NO at the wound microenvironment remains a challenge.

Reversibly "double locked" hydroxycamptothecin prodrug nanoparticles for targeted chemotherapy of lung cancer.

Prodrug assembled nanoparticles integrate the merits of both prodrug and nanoparticle, which significantly improve pharmacokinetic parameters, enhance tumorous accumulation and decrease adverse effects, while they are challenged by disassembly upon dilution in blood, masking the superiority of nanoparticles (NPs). Herein, a reversibly "double locked" hydroxycamptothecin (HCPT) prodrug nanoparticle decorated with cyclic RGD peptide (cRGD) is developed for safe and efficient chemotherapy of orthotopic lung cancer in mice. HCPT prodrug is constructed from acetal (ace)-linked cRGD-PEG-ace-HCPT-ace-acrylate polymer, which is self-assembled into the nanoparticles with "the first lock" of HCPT.

Crosslinked zwitterionic microcapsules to overcome gastrointestinal barriers for oral insulin delivery.

Oral insulin delivery has been extensively considered to achieve great patient compliance and convenience as well as favourable glucose homeostasis. However, its application is highly limited by the low insulin bioavailability owing to gastrointestinal barriers. Herein, we developed crosslinked zwitterionic microcapsules (CB-MCs@INS) based on a carboxyl betaine (CB)-modified poly(acryloyl carbonate--caprolactone) copolymer the combination of microfluidics and UV-crosslinking to improve oral insulin delivery.

Residual Stress Redistribution Analysis in the Repair Welding of AA6082-T6 Aluminum Alloy Joints: Experiment and Simulation.

Residual stress has a three-dimensional scale effect (length, depth, and width) in the process of repair welding, which has a detrimental impact on the service of the aluminum alloy welded structures in high-speed trains. This paper aims to systematically analyze the effects of the repair welding dimension on the residual stress redistribution and obtain the optimal repair welding principles. A combination of blind-hole drilling method and stress linearization in BS7910 was adopted to investigate residual stress redistribution under various repair welding dimensions.

Treatment of pyogenic liver abscess by surgical incision and drainage combined with platelet-rich plasma: A case report.

Background: Pyogenic liver abscesses are insidious in the early stage. Some cases progress rapidly, and the patient's condition can worsen and even become life-threatening if timely treatment is not provided. Surgery and prolonged antibiotic treatment are often required if the abscess is large and liquefied and becomes separated within the lumen.

Black Phosphorus-Synergic Nitric Oxide Nanogasholder Spatiotemporally Regulates Tumor Microenvironments for Self-Amplifying Immunotherapy.

The lack of tumor immunogenicity coupled with the presence of tumor immunosuppression severely hinders antitumor immunity, especially in the treatment of "immune cold" tumors. Here, we have developed a drug-free and NIR-enabled nitric oxide (NO)-releasing nanogasholder (NO@BP) composed of an outer cloak of nitrate-containing polymeric NO donor and an inner core of black phosphorus (BP) as the energy converter to spatiotemporally regulate NO-mediated tumor microenvironment remodeling and achieve multimodal therapy. Following NIR-irradiation, BP-induced photothermia and its intrinsic reducing property accelerate NO release from the outer cloak, by which the instantaneous NO burst concomitant with mild photothermia, on the one hand, induces immunogenic cell death (ICD), thereby provoking antitumor responses such as the maturation of dendritic cells (DCs) and the infiltration of cytotoxic T lymphocytes (CTLs); on the other hand, it reverses tumor immunosuppression via Treg inhibition, M2 macrophage restraint, and PD-L1 downregulation, further strengthening antitumor immunity.

Recent advances on next generation of polyzwitterion-based nano-vectors for targeted drug delivery.

Poly (ethylene glycol) (PEG)-based nanomedicines are perplexed by the challenges of oxidation damage, immune responses after repeated injections, and limited excretion from the body. As an alternative to PEG, bioinspired zwitterions bearing an identical number of positive and negative ions, exhibit exceptional hydrophilicity, excellent biomimetic nature and chemical malleability, endowing zwitterionic nano-vectors with biocompatibility, non-fouling feature, extended blood circulation and multifunctionality. In this review, we innovatively classify zwitterionic nano-vectors into linear, hyperbranched, crosslinked, and hybrid nanoparticles according to different chemical architectures in rational design of zwitterionic nano-vectors for enhanced drug delivery with an emphasis on zwitterionic engineering innovations as alternatives of PEG-based nanomedicines.

Cascade-Responsive Hierarchical Nanosystems for Multisite Specific Drug Exposure and Boosted Chemoimmunotherapy.

The precise delivery of multiple drugs to their distinct destinations plays a significant role in safe and efficient combination therapy; however, it is highly challenging to simultaneously realize the targets and overcome the intricate biological hindrances using an all-in-one nanosystem. Herein, a cascade-responsive hierarchical nanosystem containing checkpoint inhibitor anti-PD-L1 antibody (αPD-L1) and paclitaxel (PTX) is developed for spatially programed delivery of multiple drugs and simultaneously overcoming biological pathway barriers. The hierarchical nanoparticles (MPH-NP@A) are composed of pH-sensitive hyaluronic acid-acetal-PTX prodrugs (HA--PTX(SH)) chaperoned by αPD-L1 and metalloproteinase-9 (MMP-9)-responsive outer shells, which could be fast cleaved to release αPD-L1 in the tumor microenvironment (TME).

Multi-functional polymeric micelles for chemotherapy-based combined cancer therapy.

Currently, the therapeutic performance of traditional mono-chemotherapy on cancers remains unsatisfactory because of the tumor heterogeneity and multidrug resistance. In light of intricate tumor structures and distinct tumor microenvironments (TMEs), combinational therapeutic strategies with multiple anticancer drugs from different mechanisms can synergistically optimize the outcomes and concomitantly minimize the adverse effects during the therapy process. Extensive research on polymeric micelles (PMs) for biomedical applications has revealed the growing importance of nanomedicines for cancer therapy in the recent decade.

The optimal structural analysis of cobalt-chromium alloy (L-605) coronary stents.

A coronary stent is a conventional medical device used in percutaneous coronary intervention (PCI), and its mechanical properties have become one of the critical factors to determine the effect of surgical treatment. Based on the existing cobalt-chromium (CO-Cr) alloy L605 coronary stent, this paper established an integrated finite element model of the stent-balloon-compression shell to simulate the stent bundle expansion test and crush resistance test with parallel plates. We verified the accuracy of the analytical model by comparing the simulation results with experimental results.

Synthesis of monodisperse spherical AgNPs by ultrasound-intensified Lee-Meisel method, and quick evaluation via machine learning.

Due to the high reactivity of Ag and uncontrolled growth process, the AgNPs produced by conventional Lee-Meisel method always exhibited larger particle size (30-200 nm) and polydisperse morphology (including spherical, triangular, and rod-like shape). An ultrasound-intensified Lee-Meisel (UILM) method is developed in this study to environmental-friendly and controllable synthesize monodisperse spherical AgNPs (~3.7 nm).

Salt Effect on the Isobaric Vapor-Liquid Equilibrium Study of Binary Mixtures HO-NMP (-Methyl-2-pyrrolidone).

To study the salt effect of recovering -methyl-2-pyrrolidone (NMP) from the waste liquid produced in the polyphenylene sulfide (PPS) synthesis process, this study presents vapor-liquid equilibrium (VLE) measurement and correlation for water + NMP, water + NMP + lithium chloride, and water + NMP + sodium chloride at = 101.3 kPa. The salt effect is discussed and the salts follow the order of lithium chloride > sodium chloride.