Short Retention Time Research Articles

Metal ion-induced multi-layer coatings improves gastrointestinal resistance of Lactiplantibacillus plantarum and biosafety evaluation

Probiotics provide numerous health benefits; however, their low survival rate in gastric acid and short retention time in the intestine are major obstacles to their effective utilization. Here, a simple yet effective novel probiotic multilayer coating consisting of Fe3+-protocatechuic acid (PCA) crosslinked network and Ca2+-induced sodium alginate (SA) for arming Lactiplantibacillus plantarum (LP) was developed. The Fe3+-PCA and SA coating process did not affect the normal growth of probiotics. Electron microscopy experiments confirmed the feasibility of this coating strategy. In vitro simulations of gastric acid and bile salt environments demonstrated that SA-PCA coating could enhance probiotics' resistance to gastrointestinal digestion and protect against damage from ethanol and antibiotics. In vivo survival experiments further showed that SA-PCA coating improved the probiotic survival rates. Biosafety experiments indicated that this coating strategy exhibited good biosafety. This study introduces a novel conservation strategy in probiotic delivery, providing effective protection for probiotics and offering theoretical references for developing innovative approaches to alleviate related diseases.

Injectable Hyaluronic Acid-Based Hydrogels for Rapid Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is a widely used procedure for the treatment of early and precancerous gastrointestinal lesions and has become the standard treatment. In this procedure, the commonly used materials have a short retention time and a limited lifting capacity, which will prolong the duration of the ESD procedure. Furthermore, these liquids tend to diffuse after ESD surgery, failing to adequately protect the wound. Therefore, we designed and developed injectable hydrogels based on hyaluronic acid. A series of oxidized hyaluronic acid (OHA) and hydrazide hyaluronic acid (AHA) were synthesized, and 16 kinds of injectable hydrogels were fabricated to investigate the effects of molecular structures on the properties of the hydrogels. Among these, the O1A3 hydrogel exhibited a suitable injection performance, gelation time, and mechanical properties, along with good blood and cell compatibility in vitro. Subsequently, in a porcine model of the ESD procedure, the results demonstrated that the O1A3 hydrogel exhibited a good retention time and lifting performance while also significantly reducing the operation time from 1-2 h to ∼10 min. Furthermore, the adhesive property of the O1A3 hydrogel on small bleeding spots and wounds could be observed, which was beneficial in protecting the wound from the complex environment of the gastrointestinal tract. The present work of injectable hyaluronic acid-based hydrogels could be promising to improve the efficiency of ESD surgery.

Hyaluronic acid-based nanoparticles loaded with curcumin and ranibizumab for treating keratitis and anti-neovascularization

ABSTRACT The facilitation of targeted drug delivery within the ocular region presents a formidable challenge owing to its intricate physiological structure, which confers a biological barrier. This barrier is characterised by short retention times, diminished drug accumulation, and suboptimal bioavailability. To overcome these limitations, this study aimed to develop a hyaluronic acid-based nanoparticulate system encapsulating curcumin (CUR) and ranibizumab (RAN), designated as CUR-RAN@NPs with a uniform distribution of particle size and exhibited the capacity for sustained release of both CUR and RAN. The evaluation of biosafety and biocompatibility using cytotoxicity assays indicated that CUR-RAN@NPs are non-toxic and biologically compatible. Consequently, the CUR-RAN@NPs have promising potential for the advancement of ocular drug delivery systems. Finally, CUR-RAN@NPs demonstrated exceptional antibacterial activity and inhibition of neovascularization, thereby underscoring their therapeutic potential in ophthalmic applications.

Green RP-HPLC method for the estimation of carfilzomib in bulk, protein nanocarriers and human plasma: Application of chemometrics and Monte-Carlo simulations

Carfilzomib is a tetrapeptide epoxyketone that has shown potential clinical outcomes in the treatment of multiple myeloma. However, inaccuracies in quantifying such peptide drug products have arisen due to poor stability, low solubility, time-consuming techniques, complex physicochemical properties, and use of non-green solvents with less recyclability. This provides a substantial urge to develop an ecological and sensitive analytical method for quantifying peptide drugs from matrix formulation and biological samples in early as well as lateral stages of product development in pharma industries. As a result, the study aimed to develop a robust ecological method for estimation of carfilzomib via Green RP-HPLC using analytical quality by design (AQbD) paradigms with specific application in protein nanoparticles and biological matrix. Initially, an appropriate wavelength for quantification of carfilzomib was chosen using principal component analysis (PCA) as a chemometric tool.Risk assessment followed by factor screening studies using 8-factor Placket-Burman Design aided in earmarking critical method parameters (CMPs) affecting critical analytical attributes (CAAs). Further, Central Composite Design (CCD) was employed for design space optimisation to demarcate optimum chromatographic conditions, which were corroborated for robustness using Monte-Carlo simulations. The method was validated as per ICH Q2 (R1), followed by quantifying the greenness of the method using Green Assessment tools. The method optimisation resulted in the optimal chromatographic conditions using Green RP-HPLC. The chromatographic system was equipped with a Phenomenex Aeris Peptide-XC C18 column (150 × 4.6 mm × 5 µm), and the mobile phase was composed of isopropanol:methanol:0.1 M PBS (pH 5.5 adjusted using 0.1 % formic acid) (35:45:20v/v), with a 1 ml/min flow rate at a 210 nm ʎmax. The optimised chromatographic conditions resulted in a short retention time (RT) of 4.95 mins, 0.87 tailing factor (TF), 4,875,122 peak area (PA), and 8995 theoretical plate count (TPC). The method demonstrated linearity in a wide range of concentrations (0.1–20 µg/ml) with a correlational coefficient of 0.997 and < 2 % RSD. The method unearthed a high precision rate with more than 95 % of drug recovery in protein nanoparticles and human plasma, thereby confirming the accuracy and sensitivity of the developed method. Chemometrics and Monte-Carlo simulations ratified the robustness and sensitivity of the developed analytical method of Carfilzomib with established greenness and a high degree of practical utility in protein-based nano formulations and human plasma matrix for life cycle product development.

Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with 213Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors.

Radiopharmaceutical therapies (RPTs) based on fibroblast activation protein (FAP) and FAP inhibitors (FAPIs) are a new option for progressive metastatic cancer in patients pretreated multiple times. To date, published in-human data refer to initial experiences with β-emitting 90Y- and 177Lu-based RPT. However, the short tumor retention time of FAPI ligands is considered a major limitation of FAPI RPT. Therefore, fractionated FAPI RPT with 213Bi, an α-emitter with a half-life of 46 min, appears to be a promising FAPI RPT regimen. Here, we report on our initial experiences with regard to the feasibility, tolerability, and response of fractionated 213Bi-FAPI-46 RPT. Methods: Six patients (4 women and 2 men) with progressive metastatic solid tumors (3 colon cancer, 1 anal cancer, 1 breast cancer, and 1 prostate cancer) aged 16-77 y were treated with a mean of 1,609 MBq of 213Bi-FAPI-46, fractionated into 53 single applications (range, 5-12 RPT applications per patient; mean, 8.8 applications) over a period of up to 107 h per patient. Of the 6 patients, 4 patients received adjuvant treatment with pembrolizumab. 18F-FDG (4 patients) and 68Ga-FAPI-46 (5 patients) PET/CT scans were performed before and after RPT. PET images were assessed visually and by calculating total lesion glycolysis and total lesion FAPI. Results: RPT with 213Bi-FAPI-46 was well tolerated without adverse side effects. In terms of visual response assessment, there was 1 partial response (16.7%), 1 patient with stable disease (16.7%), and 4 patients with progressive disease (66.7%). Concordantly, total lesion glycolysis and total lesion FAPI were decreased in the responding patient (not applicable and -24.3%, respectively), slightly decreased in the patient with stable disease (-10.6% and -5.9%, respectively), and increased in the 4 patients with progression (mean, +104.4% and +321.3%, respectively). Conclusion: Fractionated FAPI RPT with the short-half-life α-emitter 213Bi-FAPI-46 is a promising approach that matches the pharmacokinetics of FAPI-46 better than the 177Lu- or 90Y-labeled compounds. In this pilot project, fractionated RPT with 213Bi-FAPI-46 showed good clinical tolerability and even led to regressive or stable disease in the short term in 2 of 6 patients. Further studies with larger patient cohorts are required to evaluate the actual efficacy and long-term effects of this variant of FAPI RPT.

Pitaya-Inspired Metal-Organic Framework Nanozyme for Multimodal Imaging-Guided Synergistic Cuproptosis, Nanocatalytic Therapy, and Photothermal Therapy.

Nature often provides invaluable insights into technological innovation and the construction of nanomaterials. Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal-organic framework (MOF)-encapsulated CuS nanoparticles (NPs) is developed. This design effectively addresses the challenge of short retention time afforded by CuS NPs for therapeutic and imaging purposes. The MOF acts as the "pitaya pulp" protecting the internal CuS NPs ("pitaya seeds"), thereby increasing their retention time in vivo. This system exhibits triple-enzyme-mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging-guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis-related therapy. The exceptional enzyme-mimicking activities of superoxide dismutase, catalase, and peroxidase not only produce oxygen to alleviate hypoxia but also generate a reactive oxygen species (ROS) storm for effective tumor destruction. By combining these multienzymatic properties, superior photothermal performance, and Cu-induced cuproptosis, nanozyme-treated mice exhibited an 84% inhibition of tumor growth-approximately double the effect observed in mice treated with CuS NPs alone. This study presents a smart strategy for integrating imaging with therapeutic modalities, achieving exceptional outcomes for precise imaging-guided tumor therapy.

Use of embedding immobilized biofillers to improve hydrolysis acidification efficiency in domestic wastewater treatment

This study evaluated the effectiveness of embedding immobilization technology in wastewater treatment and its capacity to enhance the hydrolysis acidification process. Based on this technology, a stable anaerobic environment has been maintained. Results showed that the rates of dissolved organic nitrogen (DON) and dissolved organic phosphorus (DOP) conversion both exceeded 98 % under short hydraulic retention time (HRT = 2h) and ambient temperature. Notably, acetic acid and propionic acid comprised up to 90.9 % of the total volatile fatty acids in the effluent, providing suitable carbon sources for downstream denitrification. 16S rRNA gene sequencing indicated that biofillers effectively enriched and retained functional bacteria, causing norank_Anaerolineaceae (11.6 %-29.7 %) and norank_Bacteroidetes_vadinHA17 (10.8 %-14.9 %) as the dominant genera in the reactor, which were crucial for refractory organic matter degradation. Immobilized biofillers effectively improved wastewater biodegradability, supporting a stable microbial community with high DON and DOP conversion rates as well as increased VFA accumulation.

Ferric Iron/Shikonin Nanoparticle-Embedded Hydrogels with Robust Adhesion and Healing Functions for Treating Oral Ulcers in Diabetes.

Oral ulcers can be addressed using various biomaterials designed to deliver medications or cytokines. Nevertheless, the effectiveness of these substances is frequently limited in many patients due to poor adherence, short retention time in the mouth, and less-than-optimal drug efficacy. In this study, a new hydrogel patch (FSH3) made of a silk fibroin/hyaluronic acid matrix with light-sensitive adhesive qualities infused with ferric iron/shikonin nanoparticles to enhance healing effects is presented. Initially, this hydrogel forms an adhesive barrier over mucosal lesions through a straightforward local injection, solidifying when exposed to UV light. Subsequently, FSH3 demonstrates superior reactive oxygen species elimination and near-infrared photothermal bactericidal activity. These characteristics support bacterial elimination and regulate oxidative levels, promoting a wound's progression from inflammation to tissue regeneration. In a diabetic rat model mimicking oral ulcers, FSH3 significantly speeds up healing by adjusting the inflammatory environment of the injured tissue, maintaining balance in oral microbiota, and promoting faster re-epithelialization. Overall, the light-sensitive FSH3 hydrogel shows potential for rapid wound recovery and may transform therapeutic methods for managing oral ulcers in diabetes.

Enzyme-responsive microgel with controlled drug release, lubrication and adhesion capability for osteoarthritis attenuation

The treatment of osteoarthritis (OA) remains challenging due to the narrow therapeutic window and rapid clearance of therapeutic agents, even with intra-articular administration, resulting in a low treatment index. Recent advancements in local drug delivery systems have yet to overcome the issues of uncontrolled burst release and short retention time, leading to suboptimal OA treatment outcome. Herein, we developed a methacrylate-crosslinking hyaluronic acid (HA) microgel (abbreviated as CXB-HA-CBP) that covalently conjugates the anti-inflammatory drug celecoxib (CXB) via a metalloproteinase-2 (MMP-2)-responsive peptide linker (GGPLGLAGGC) and a collagen II binding peptide (WYRGRLC). The GGPLGLAGGC linker is specifically cleaved by the overexpressed MMP-2 enzyme within the OA joint, enabling the sustained and on-demand release of CXB entity. The synergistic action of CXB and HA effectively inhibited macrophage activation and reduced the production of pro-inflammatory cytokines, protecting chondrocytes from damage. Furthermore, the collagen II peptide introduced on the microgel surface enabled a cartilage-binding function to form an artificial lubrication microgel layer on the cartilage surface to reduce cartilage wear. The CXB-HA-CBP microgel showed an extended retention time of up to 18 days in the affected joint, leading to an effective OA treatment in rats. This sophistically designed microgel, characterized by the prolonged retention time, sustained drug delivery, and enhanced lubrication, presents a promising biomedicine for OA treatment. Statement of significanceA new methacrylate-crosslinking hyaluronic acid (HA) microgel, covalently conjugated with the celecoxib (CXB)-GGPLGLAGGC and the collagen II binding peptide (CBP, peptide sequence: WYRGRLC), was developed. The overexpressed MMP-2 in OA joint cleaved the GGPLGLAGGC linker to trigger the CXB moiety release. Besides, the CBP on the surface of microgels enabled a cartilage-attaching ability, resulting in a prolonged retention time and an improved lubrication property in joint. This advanced drug-loading microgel remarkably reduced macrophage activation and pro-inflammation cytokine production, while protecting the chondrocytes via a dual action of CXB and HA. This study demonstrated that the enzyme-responsive drug-loading microgel could serve as an platform to efficiently attenuate osteoarthritis.

Why aphid virus retention needs more attention: Modelling aphid behaviour and virus manipulation in non-persistent plant virus transmission.

Plant viruses threaten food security and are often transmitted by insect vectors. Non-persistently transmitted (NPT) plant viruses are transmitted almost exclusively by aphids. Because virions attach to the aphid's stylet (mouthparts) and are acquired and inoculated via brief epidermal probes, the aphid-virus interaction is highly transient, with a very short aphid virus retention time. Many NPT viruses manipulate their host plant's phenotype to change aphid behaviour to optimise virus transmission. Epidemiological models of this have overlooked a key feature of aphid NPT virus retention: probing or feeding on a plant causes aphids to lose the virus. Furthermore, experimental studies suggest aphids could possibly inoculate multiple healthy plants within one infective period if they do not feed. Consequences of this for virus manipulation of host plant phenotype have not been explored. Our new compartmental epidemiological model includes both behaviour-based aphid dispersal and infectivity loss rates, and the ability of infective aphids to probe multiple plants before virus loss. We use our model to explore how NPT virus-induced host phenotypes affect epidemic outcomes, comparing these results to representative previous models. We find that previous models behave fundamentally differently and underestimate the benefit of an 'attract-and-deter' phenotype, where the virus induces increased aphid attraction to infected plants but deters them from prolonged feeding. Our results also highlight the importance of characterising NPT virus retention upon the aphid during probing. Allowing for multiple infective probes increases disease incidence and the effectiveness of virus manipulation, with implications for epidemic prediction and control.

A near-infrared fluorescent probe with assembly/aggregation-induced retention effect for specific diagnosis of metastasis and image-guided surgery in breast cancer

Image-guided surgery is crucial for achieving complete tumor resection, reducing postoperative recurrence and improving patient survival. However, current clinical near-infrared fluorescent probes, such as indocyanine green (ICG), face two main limitations: 1) lack of active tumor targeting, and 2) short retention time in tumors, which restricts real-time imaging during surgery. To address these issues, we developed a near-infrared fluorescent probe capable of in situ nanofiber formation within tumor lesions. This probe actively targets the integrin αvβ3 receptors overexpressed on breast cancer cells and exhibits assembly/aggregation-induced retention effects at the tumor site, significantly extending the imaging time window. Additionally, we found that the probe's fluorescence intensity can be enhanced under receptor induction. Due to its excellent tumor specificity and sensitivity, 1FCG-FFGRGD not only identifies primary breast cancer but also precisely locates smaller lymph node metastases and detects sub-millimeter peritoneal metastases. In summary, this near-infrared probe, leveraging assembly/aggregation-induced retention effects, holds substantial potential for various biomedical applications.

Antimicrobial Peptide Hydrogel with pH-Responsive and Controllable Drug Release Properties for the Efficient Treatment of Helicobacter pylori Infection.

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

In-situ hydrogen-generating injectable short fibers for osteoarthritis treatment by alleviating oxidative stress

Hydrogen (H₂) has great potential in the treatment of osteoarthritis, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study developed a short-fiber injectable material that can continuously generate hydrogen in situ to eliminate reactive oxygen species (ROS), alleviate oxidative stress and inflammation, and promote tissue repair. We prepared H–Si nanosheets with high hydrogen generation efficiency using a wet chemical exfoliation method and combined them with GelMA short fibers via electrospinning technology, achieving the in situ delivery of H–Si nanosheets and regulated hydrogen generation rate through the encapsulation and degradation of GelMA, ultimately achieving continuous and controlled hydrogen supply and stable therapeutic effects for osteoarthritis. In vitro and in vivo experiments confirmed the safety and efficacy of this material. The results showed that the material could continuously and efficiently generate hydrogen in simulated physiological environments (100 mg of material could generate 8.6 % hydrogen), effectively eliminate cellular reactive oxygen species (ROS positive rate reduced by 85.89 %), reduce cellular senescence and apoptosis (cell death rate decreased by 52 %, SA-βgal expression decreased by 78.3 %), promote normal chondrocyte function (Col II expression increased by 67.4 %, Ki67 expression increased by 87.5 %), and improve osteoarthritis in rats (OARSI score increased by 216 %). The in situ hydrogen generation and control system designed in this study provides a new method for the hydrogen's local and stable treatment of osteoarthritis. Statement of significanceHydrogen (H₂) has great potential in the treatment of osteoarthritis by alleviating oxidative stress, but its rapid diffusion and short retention time make it difficult to exert stable therapeutic effects. This study introduces an innovative injectable material combining H–Si nanosheets and GelMA short fibers to address this issue. By enabling continuous in situ hydrogen generation, this material effectively eliminates reactive oxygen species, reduces oxidative stress and inflammation, and promotes tissue repair. In vitro and in vivo experiments demonstrate its high hydrogen generation efficiency, safety, and therapeutic efficacy, offering a promising new approach for osteoarthritis management.

Study of resistive properties and neural response of ZrO2/TiO2 heterojunction nanowire array (NWA) RRAM

Nowadays, the researcher has an eye on enhancing the performance of resistive random-access memory (RRAM) and exploring new demands and applications, particularly in the field of artificial intelligence and neural computing. It is crucially important for accurately replicating the observed plasticity within synapses to achieve superior RRAM performance in low-dimensional nanomaterials. In this work, we focus on addressing certainly unsatisfactory electrical properties of RRAM based on titanium oxide nanowire array (TiO2 NWA), for example, short retention time (∼103 s). Theoretically and experimentally, a novel and solution-based RRAM structure, namely ZrO2/TiO2(NWA), has been conducted. With the help of the ZrO2 insertion layer, the RRAM device shows impressive resistive switching characteristics, including 200 current–voltage(I-V) sweeps without degradation, increased cycling endurance (>105 cycles), and a long retention time (∼9 × 104 s). These findings hold significant implications for digital computing systems. Moreover, the successful implementation of the proposed device enables the emulation of fundamental synaptic biological features such as non-linear transmission properties, learning experiences behavior, short-term potentiation (STP) and long-term potentiation (LTP). This research provides evidence of the immense potential of the Ag/ZrO2/TiO2(NWA)/FTO RRAM device in bipolar non-volatile memory (NVM) and biomimetic neuromorphic systems.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. Statement of significanceOral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

Integrating enhanced biological phosphorus removal in adsorption-stage to treat real domestic sewage

Wastewater treatment innovation toward resource recovery facilities raises concerns about the adsorption and bio-degradation (A-B) process. This study integrated enhanced biological phosphorus removal (EBPR) into the A-stage for real domestic sewage treatment using the short sludge retention time (S-SRT) approach. The S-SRT approach resulted in outstanding phosphorus (over 90 %) and COD removal (approximately 88 %), increased sludge yield and organic matter content, and a 1.68-fold increase in energy recovery efficiency by sludge anaerobic digestion. The inhibition of nitrification relieved competition for carbon sources between denitrification and phosphorus removal, allowing for the enrichment of phosphorus-accumulating organisms (PAOs) such as Tetrasphaera and Halomonas, leading to enhanced phosphorus removal activities. Biological adsorption also plays a significant role in achieving steady phosphorus removal performance. This study demonstrates the potential of the S-SRT approach as an effective strategy for simultaneous carbon and phosphorus capture in the A-stage, contributing to energy and nutrient recovery from sewage.

Pericardial Delivery of Sodium Alginate-Infusible Extracellular Matrix Composite Hydrogel Promotes Angiogenesis and Intercellular Electrical Conduction after Myocardial Infarction.

Injectable extracellular matrix (iECM) is a versatile biological material with beneficial properties such as good degradability, promotion of cell survival, immunomodulation, and facilitation of vascular formation. However, intravenous injection of iECM faces challenges like a short retention time in vivo and low concentration at the lesion site. To address these issues, we prepared a composite hydrogel composed of sodium alginate and iECM and administered it via intrapericardial injection, forming a structure akin to cardiac patches within the pericardium. Compared with intramyocardial injection, intrapericardial injection avoids direct myocardial injury and ectopic tumor formation, offering less invasiveness and better biocompatibility. This study demonstrates that the sodium alginate/infusible extracellular matrix (SA/iECM) composite hydrogel can effectively prolong the local retention time of iECM in the heart, enhance electrical conduction between cardiomyocytes, promote angiogenesis at ischemic myocardial sites, inhibit apoptosis in the infarcted region, mitigate left ventricular remodeling postmyocardial infarction (MI), and improve cardiac function after infarction. Precise coordination of cardiomyocyte contraction and relaxation depends on the rhythmic occurrence of calcium-dependent action potentials. Cardiac dysfunction is partially attributed to the disruption of the excitation-contraction coupling (ECC) mechanism, which is associated with prolonged intracellular Ca2+ transients and alterations in contraction and relaxation Ca2+ levels. Our results show that the SA/iECM composite hydrogel improves electrical conduction, as evidenced by increased Cx43 expression and enhanced intercellular electrical connectivity. This research establishes that intrapericardial injection of a SA/iECM composite hydrogel is a safe and effective treatment modality, providing a theoretical basis for the use of biomaterials in MI therapy.

Matrix metalloproteinase 2-responsive dual-drug-loaded self-assembling peptides suppress tumor growth and enhance breast cancer therapy.

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self-assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP-2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP-2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor-associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.

Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·（m3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

A thiolated oxidized guar gum and sodium alginate dual-network microspheres with enhanced gastric acid resistance and mucoadhesion for delivery of probiotics

Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca2+ to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.