Mucus and Biofilm Penetrating Nanoplatform as an Ultrasound-Induced Free Radical Initiator for Targeted Treatment of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug-resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu3-PDA@AIPH@Fucoidan (PPAF), which consists of dopamine-modified inorganic sonosensitizers PtCu3, alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori, disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species and oxygen-independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori. In vivo experiments demonstrate that ultrasound-stimulated PPAF exhibited significant antibacterial efficacy against H. pylori. Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection.

Exosomal circMACF1 drives PI3K/AKT/mTOR-mediated autophagy suppression in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. The regulatory functions of circular RNAs (circRNAs) in cancers have been broadly reported. The hsa_circ_0011773 (circMACF1) is reported to be overexpressed in LSCC tissues, while its biological function in LSCC remains unclear. CircMACF1 expression in LSCC tissues and cells was assessed via RT-qPCR. Exosomes extracted from cells were identified by TEM and NTA. Autophagy-related proteins were tested by western blot. Confocal microscope was employed for analyzing LC3 expression. Cell proliferation, migration, and invasion were assessed by CCK-8 assay and transwell assay. The levels of main proteins on PI3K/AKT/mTOR were tested by western blot. We observed that circMACF1 was highly expressed in LSCC tissues and cells. Furthermore, circMACF1 expression was also upregulated in the exosomes derived from LSCC cells. CircMACF1 depletion promoted LC3 expression in cells. Additionally, we proved that circMACF1 knockdown suppressed LSCC cell proliferative, migratory and invasive capabilities via promoting autophagy. Exosomal circMACF1 was found to promote LSCC tumor growth. Then, we proved that circMACF1 could activate PI3K/AKT/mTOR pathway to regulate autophagy. Moreover, MACF1 was positively regulated by circMACF1 and its overexpression notably reversed the effects of circMACF1 depletion in LSCC progression. Exosomal circMACF1 can regulate PI3K/AKT/mTOR-mediated autophagy suppression to facilitate LSCC development.

2D nanomaterial-based 3D network hydrogels for anti-infection therapy.

Two-dimensional nanomaterials (2D NMs) refer to nanomaterials that possess a planar topography with a thickness of one or several atomic layers. Due to their large specific surface areas, atomic thickness, rough edges, and electron confinement in two dimensions, they have emerged as promising antimicrobial agents over antibiotics in combating bacterial infections. However, 2D NMs encounter issues such as low bio-safety, easy aggregation, and limited tissue penetration efficiency. To address these concerns, hydrogels with three-dimensional (3D) networks have been developed to encapsulate 2D NMs, aiming to enhance their biocompatibility, biodegradability, and ability to regulate and remodel the tissue microenvironment at the infected site. This review systematically summarizes the current studies on 2D NM-based antibacterial hydrogels with 3D network structures (named 2N3Hs). Firstly, we introduce the emerging types of 2N3Hs and describe their antibacterial actions. Subsequently, we discuss the applications of 2N3Hs in three biomedical fields, including wound dressing, cancer treatment, and bone regeneration. Finally, we conclude the review with current challenges and future developments for 2N3Hs, highlighting their potential as a promising choice for next-generation biomedical devices, particularly in the field of tissue engineering and regenerative medicine. This review aims to provide a comprehensive and panoramic overview of anti-infective 2N3Hs for various biomedical applications.

Reusable Zwitterionic Porous Organic Polymers for Bilirubin Removal in Serum.

Herein, we report a straightforward strategy to construct reusable, hemocompatible, and highly efficient bilirubin adsorbents by installing zwitterionic modules into a porous organic polymer (POP) for hemoperfusion application. Three types of zwitterions with different amounts are used to evaluate their impacts on the characteristics of POPs, including carboxybetaine methacrylate (CB), sulfobetaine methacrylate (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Results show that zwitterions can improve hemocompatibility, hydrophilicity, and bilirubin uptake of the POP. Among all zwitterionic POPs, POP-CB-40% exhibits the best bilirubin uptake, ∼46.5 times enhancement compared with the non-zwitterionic POP in 100% serum. This enhancement can be attributed to the improved hydrophilicity and protein resistance ability in biological solutions. More importantly, the reusability test shows that POP-CB-40% maintains ∼99% of bilirubin uptake capacity at fifth recycling in 100% serum. Findings in this work provide a guideline for the design of biocompatible and efficient POP-based bilirubin adsorbents for hemoperfusion therapy.

Validation of combined AFP, AFP-L3, and PIVKA II for diagnosis and monitoring of hepatocellular carcinoma in Chinese patients.

Background: In this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. Methods: In this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. Results: The AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. Conclusions: The AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

Black Phosphorus-Based Conductive Hydrogels Assisted by Electrical Stimulus for Skin Tissue Engineering.

Conductive hydrogels have shown great potential in wound healing and skin tissue engineering, owing to their electroactive, mechanical, and chemical properties. However, it still remains as a challenge to incorporate other functions into conductive hydrogels, such as antibacterial ability, controllable drug release, and biodegradability. In this study, a black phosphorus-based conductive hydrogel (HA-DA@BP) is prepared by an amidation reaction coupled with a coordination of Fe3+ -catechol. The hydrogel could be changed from the sol phase to the gel phase under electrical stimulus (ES). The results show that BP could be released under slight acidity, which is cell compatible but could achieve synergistic electrical antibacterial action and promote wound healing. This study proves that BP is a strong candidate for electroactive materials and provides a new insight for the development of BP-based biomedical materials in skin tissue engineering.

Functional carbohydrate-based hydrogels for diabetic wound therapy.

Diabetes wound are grave and universal complications of diabetes. Owing to poor treatment course, high amputation rate and mortality, diabetes wound treatment and care have become a global challenge. Wound dressings have received much attention due to their ease of use, good therapeutic effect, and low costs. Among them, carbohydrate-based hydrogels with excellent biocompatibility are considered to be the best candidates for wound dressings. Based on this, we first systematically summarized the problems and healing mechanism of diabetes wounds. Next, common treatment methods and wound dressings were discussed, and the application of various carbohydrate-based hydrogels and their corresponding functionalization (antibacterial, antioxidant, autoxidation and bioactive substance delivery) in the treatment of diabetes wounds were emphatically introduced. Ultimately, the future development of carbohydrate-based hydrogel dressings was proposed. This review aims to provide a deeper understanding of wound treatment and theoretical support for the design of hydrogel dressings.

Zwitterionic Biomaterials.

The term "zwitterionic polymers" refers to polymers that bear a pair of oppositely charged groups in their repeating units. When these oppositely charged groups are equally distributed at the molecular level, the molecules exhibit an overall neutral charge with a strong hydration effect via ionic solvation. The strong hydration effect constitutes the foundation of a series of exceptional properties of zwitterionic materials, including resistance to protein adsorption, lubrication at interfaces, promotion of protein stabilities, antifreezing in solutions, etc. As a result, zwitterionic materials have drawn great attention in biomedical and engineering applications in recent years. In this review, we give a comprehensive and panoramic overview of zwitterionic materials, covering the fundamentals of hydration and nonfouling behaviors, different types of zwitterionic surfaces and polymers, and their biomedical applications.

A balanced charged hydrogel with anti-biofouling and antioxidant properties for treatment of irradiation-induced skin injury.

Skin injury caused by large doses of ionizing radiation is the common and severe side effect of radiotherapy. However, its therapeutic efficacy is always hindered by early reactive oxygen species generation, repetitive inflammatory microenvironment and bacterial infection risk. Herein, we report an anti-biofouling hydrogel with anti-inflammation and anti-oxidative properties for the treatment of irradiation-induced skin injury. The anti-biofouling hydrogel can be achieved by balancing oppositely charged alginate, hyaluronic acid (HA) and polylysine (PLL) at the optimal ratio, which effectively resist protein and bacterial adhesion, and evades immune response. Moreover, curcumin and epigallocatechin gallate (EGCG) can be facially encapsulated and substantially released from the hydrogel. Results showed that the resulting AHP-Cur/EGCG hydrogel can significantly weaken the development of skin injury and accelerate its healing process by alleviating inflammation, scavenging ROS and promoting angiogenesis. Therefore, the findings presented in this work provide an effective strategy for clinical management and treatment of ionizing radiation-induced skin injury.

Antifouling Fibrous Membrane Enables High Efficiency and High-Flux Microfiltration for Water Treatment.

Membrane biofouling has long been a major obstacle to highly efficient water treatment. The modification of the membrane surface with hydrophilic materials can effectively enhance biofouling resistance. However, the water flux of the membranes is often compromised for the improvement of antifouling properties. In this work, a composite membrane composed of a zwitterionic hydrogel and electrospinning fibers was prepared by a spin-coating and UV cross-linking process. At the optimum conditions, the composite membrane could effectively resist the biofouling contaminations, as well as purify polluted water containing bacteria or diatoms with a high flux (1349.2 ± 85.5 L m-2 h-1 for 106 CFU mL-1 of an Escherichia coli solution). Moreover, compared with the commercial poly(ether sulfone) (PES) membrane, the membrane displayed an outstanding long-term filtration performance with a lower water flux decline. Therefore, findings in this work provide an effective antifouling modification strategy for microfiltration membranes and hold great potential for developing antifouling membranes for water treatment.

Diagnostic value of combined serological markers in the detection of acute cerebral infarction.

ABSTRACT: To evaluate the value of the combination schemes of 10 serological markers in the clinical diagnosis of acute cerebral infarction.The level of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, homocysteine (HCY), lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were analyzed in 154 patients with acute ischemic cerebral infarction. The optimized diagnostic combination for acute cerebral infarction was explored by calculating the maximum area under the receiver operating characteristic curves (AUC).The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, HCY, lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were significantly higher in the patient vs the control group. Moreover, the positive rate of HCY reached 89.9%. The analysis of the receiver operating characteristic curve of each index and their combinations showed that the minimum AUC of HDL-C alone was 0.543, while the maximum AUC of HCY was 0.853. A multiple logistic regression analysis indicated that HDL-C was a slightly significant variate in the diagnosis of acute cerebral infarction.The value of individual serological markers in the diagnosis of acute cerebral infarction was slightly significant, while the combination of the markers significantly improved the efficiency of its diagnosis.

2D Black Phosphorus-Based Cytomembrane Mimics with Stimuli-Responsive Antibacterial Action Inspired by Endotoxin-Associated Toxic Behavior.

Biomimetic membrane materials have been widely explored and developed for drug loading and tissue engineering applications due to their excellent biocompatibility and abundant reaction sites. However, novel cytomembrane mimics have been lacking for a long time. In this study, black phosphorus (BP) was used as the foundation for a new generation of promising cytomembrane mimics due to its multiple similarities to cytomembranes. Inspired by the dual function of endotoxins on membranes, we prepared a BP-based cytomembrane mimic with controllable antibacterial ability via electrostatic interaction between BP and [1-pentyl-1-quaternary ammonium-3-vinyl-imidazole]Br ([PQVI]Br). The release of PQVI could be manipulated in different conditions by adjusting the electrostatic force, thereby achieving controllable antibacterial ability. This report confirms the possibility of using BP as a new material to mimic cytomembranes and provides a new concept of controllable antibacterial action based on endotoxins.

A near-infrared light-mediated antimicrobial based on Ag/Ti3C2Tx for effective synergetic antibacterial applications.

Designing antimicrobials with high efficiency and long-term antibacterial activity is an imperative issue. We found that the antimicrobial effect of Ti3C2Tx and Ag/Ti3C2Tx could be significantly strengthened upon near-infrared light exposure. The synergistic antibacterial mode of the photothermal bactericidal effect and intrinsic bacterial activity have been revealed, which confirms that the Ti3C2Tx MXene is an excellent near-infrared light-mediated nanoplatform for antibacterial applications. To further test the antibacterial effect in practical applications, Ag/Ti3C2Tx embedded hydrogels were used as wound dressings in a wound model experiment. They exhibit outstanding bacterial inhibition and wound healing performance with near-infrared light exposure. This work inspires us to explore the MXene-based photothermal platform in terms of antibacterial application.

A zwitterionic hydrogel coated titanium surface with high-efficiency endothelial cell selectivity for rapid re-endothelialization.

Coronary stent implantation is an effective procedure for percutaneous coronary intervention treatment. However, its long-term safety and efficacy are still hindered by the in-stent restenosis and late thrombus formation. Herein, an anti-biofouling and endothelial cell selective zwitterionic hydrogel coating was developed to simultaneously enhance the nonspecific resistance and rapid re-endothelialization of the titanium surface. An endothelial cell selective peptide, REDV, could be simply conjugated on the zwitterionic carboxybetaine (CB) hydrogel to prepare the REDV/CB coating. It was found that the REDV/CB hydrogel layer maintained antifouling properties, which could inhibit the protein adsorption, bacterial adhesion, platelet activation and aggregation, and smooth muscle cell proliferation. More importantly, the co-culture study confirmed that the conjugated REVD peptide could specifically capture endothelial cells and promote their migration and proliferation, and simultaneously decrease the adhesion and proliferation of smooth muscle cells. Therefore, the antifouling and endothelial cell selective coating proposed in this work provides a promising strategy to develop an intravascular stent for promoted re-endothelialization and inhibited neointimal hyperplasia in clinical applications.

MOF-Based Antibiofouling Hemoadsorbent for Highly Efficient Removal of Protein-Bound Bilirubin.

A metal-organic framework (MOF)-based antibiofouling hemoadsorbent (PCB-MIL101) was developed through a facile encapsulation of MIL-101(Cr) in zwitterionic poly carboxybetaine (PCB) hydrogel. PCB-MIL101 possessed strong mechanical strength and superior hemocompatibility, ensuring its safety in hemoperfusion applications. In addition, it showed efficient and effective adsorption toward bilirubin (BR), and its maximum adsorption capacity was ∼583 mg g-1. Moreover, due to the protection of antibiofouling PCB hydrogel, PCB-MIL101 showed ability to resist protein adsorption, thus working effectively to remove BR molecules from their binding albumin in biological solutions. The finding in this study provides a novel insight into developing MOF-based hemoadsorbents for the improvement of hemoperfusion therapies.

Influence of divalent cations on the biofouling behaviors of alginate hydrogels.

Alginate is one of the most favorable materials in many biomedical applications. The mechanical properties of alginate hydrogels can be easily tailored by adding different concentrations of divalent cations. In this work, we demonstrate that the method can also notably influence the biofouling behaviors of alginate hydrogels. A series of alginate hydrogels was prepared by tuning the concentrations of two types of divalent cation (Ca2+ or Ba2+). It was found that the biofouling behaviors of the hydrogels exhibited a 'U' curve tendency with the cation concentrations. Interestingly, we found that in optimal conditions ([Ca2+] = 0.9 mM or [Ba2+] = 0.54 mM), the resultant Ca0.9- and Ba0.54-alginate hydrogels were able to achieve negligible adhesion of the proteins and bacteria. Moreover, these two formulations were also able to prevent inflammatory responses at least 4 weeks after subcutaneous implantation in a mouse model. The findings in this work provide more insights into the design and development of appropriate alginate hydrogels for different applications.

Dimethyl Sulfoxide-Free Cryopreservation of Chondrocytes Based on Zwitterionic Molecule and Polymers.

Cartilage tissue engineering highly relies on the ability to store and transport chondrocytes in order to be clinically successful. Cryopreservation is a most reliable technology for chondrocyte storage, but it suffers from the intrinsic toxicity of current state-of-the-art cryoprotectant, dimethyl sulfoxide (DMSO). In this work, we used the first fully zwitterionic compound-based approach for effective chondrocyte cryopreservation. A zwitterionic molecule combined with zwitterionic polymers could balance intra/extracellular osmotic stress and prevent ice formation, which were the keys of successful cryopreservation. Moreover, this zwitterionic combination showed noncytotoxicity due to its high biocompatibility, superior to cytotoxic DMSO. On the basis of these performances, chondrocytes could be well cryopreserved (∼90% post-thaw survival efficiency) for a long time without any addition of DMSO, and the recovered cells could maintain their normal functionalities. In view of the association between polymer molecular weight and cryopreservation efficacy, further mechanism of cryoprotection provided by zwitterionic molecule/polymer was proposed. This work opens a new window of opportunity for DMSO-free cryopreservation using biocompatible zwitterionic materials.

Beetle-Inspired Hierarchical Antibacterial Interface for Reliable Fog Harvesting.

The microdroplets in fog flow have been considered as an important resource for supplying fresh drinking water. Most of the reported works of fog collection focus on the water-collecting ability rather than the environmental reliability of selected materials. In this work, a beetle-inspired hierarchical fog-collecting interface based on the antibacterial needle-array (ABN) and hydrophilic/hydrophobic cooperative structure is displayed. The hydrophilic ABN is coated with zwitterionic carboxybetaine (CB) brushes that endow the fog collector with a long-term cleaning in harsh environment. Due to its strong affinity to water molecules, the tilted needles with a CB coating can facilitate the capture of fog and the rapid delivery of condensed water driven by gravity. After being transported to the connected hydrophobic sheet, the collected droplets can be rapidly detached and stored in the container, achieving a high fog-harvesting rate. Furthermore, CB-patterned channels are integrated on the hydrophobic sheet for the pathway-controlled water delivery. The CB coating is able to efficiently resist bacterial adhesion and contamination during fog harvesting, protecting the device from microbiological corrosion. The current design provides a promising method to incorporate antibacterial ability into fog collectors, which offer great opportunity to develop water harvesters for real-world applications.

Hemocompatible hemoadsorbent for effective removal of protein-bound toxin in serum.

Resin hemoperfusion is a life-saving treatment for drug intoxication or hepatic failure of patients. However, current resin adsorbents exhibit a limited hemocompatibility or low adsorption efficiency, representing a major roadblock to successful clinical applications. In this work, we developed a hemocompatible and effective hemoadsorbent based on polystyrene resin (H103) microparticles encapsulated in anti-biofouling zwitterionic poly(carboxybetaine) (PCB) hydrogels. Apart from a strong mechanical stability, this PCB-based adsorbent (PCB-H103) exhibited excellent hemocompatibility (hemolysis ratio was ∼0.64%), which was attributed to the anti-biofouling property of PCB hydrogel. In addition, it can efficiently adsorb both small and middle molecular weight molecules in phosphate-buffered saline, and the efficiencies were significantly higher than poly(ethylene glycol) methacrylate-based and poly(2-hydroxyethyl methacrylate)-based adsorbent counterparts, indicating the favorable permeability of PCB hydrogel coating. More importantly, PCB-H103 could effectively remove protein-bound toxins including phenol red and bilirubin in bovine serum albumin solution or even in 100% fetal bovine serum (FBS). In 100% FBS, the adsorption capacity of PCB-H103 towards bilirubin was 8.3 times higher than that of pristine clinical-scale resin beads. Findings in this work may provide a new strategy for the development of modern resin hemoperfusion technology.

A Robust Cotton Textile-Based Material for High-Flux Oil-Water Separation.

PDMS-based materials have been extensively studied in oil-water separation. However, their successful application is commonly limited by low efficiency, vulnerability to acid/alkali, complex processing procedures, incapability for emulsion separation, etc. Here, a highly durable and robust separation material is developed by coating PDMS-based copolymers on cotton textiles with a facile sol-gel approach. Solely driven by gravity, this new material not only can enable effective separation of oil-water mixture with a flux as high as ∼7500 L m-2 h-1 but also can separate surfactant-stabilized water-in-oil emulsion. Moreover, it remains fully functional even in the environments with high concentrations of acid, alkali, or salt. This novel and versatile strategy holds great promise to be widely used in practical applications of oil-water separation, including oil/chemical spill accidents and industrial sewage emission.