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Camptothecin (CPT) is a highly cytotoxic molecule with excellent antitumor activity against various cancers. However, its clinical application is severely limited by poor water solubility, easy inactivation, and severe toxicity. Structural modifications and nanoformulations represent two crucial avenues for camptothecin's development. However, the potential for further structural modifications is limited, and camptothecin nanoparticles fabricated via physical loading have the drawbacks of low drug loading and leakage. Prodrug‐based CPT nanoformulations have shown unique advantages, including increased drug loading, reduced burst release, improved bioavailability, and minimal toxic side effects. Stimulus‐responsive CPT nano‐prodrugs that respond to various endogenous or exogenous stimuli by introducing various activatable linkers to achieve spatiotemporally responsive drug release at the tumor site. This review comprehensively summarizes the latest research advances in stimulus‐responsive CPT nano‐prodrugs, including preparation strategies, responsive release mechanisms, and their applications in cancer therapy. Special focus is placed on the release mechanisms and characteristics of various stimulus‐responsive CPT nano‐prodrugs and their application in cancer treatment. Furthermore, clinical applications of CPT prodrugs are discussed. Finally, challenges and future research directions for CPT nano‐prodrugs are discussed. This review to be valuable to readers engaged in prodrug research is expected. [ABSTRACT FROM AUTHOR]

Inflammation‐associated diseases are very common clinically with a high incidence; however, there is still a lack of effective treatments. Cell‐biomimetic nanoplatforms have led to many breakthroughs in the field of biomedicine, significantly improving the efficiency of drug delivery and its therapeutic implications especially for inflammation‐associated diseases. Macrophages are an important component of immune cells and play a critical role in the occurrence and progression of inflammation‐associated diseases while simultaneously maintaining homeostasis and modulating immune responses. Therefore, macrophage‐biomimetic nanoplatforms not only inherit the functions of macrophages including the inflammation tropism effect for targeted delivery of drugs and the neutralization effect of pro‐inflammatory cytokines and toxins via membrane surface receptors or proteins, but also maintain the functions of the inner nanoparticles. Macrophage‐biomimetic nanoplatforms are shown to have remarkable therapeutic efficacy and excellent application potential in inflammation‐associated diseases. In this review, inflammation‐associated diseases, the physiological functions of macrophages, and the classification and construction of macrophage‐biomimetic nanoplatforms are first introduced. Next, the latest applications of different macrophage‐biomimetic nanoplatforms for the treatment of inflammation‐associated diseases are summarized. Finally, challenges and opportunities for future biomedical applications are discussed. It is hoped that the review will provide new ideas for the further development of macrophage‐biomimetic nanoplatforms. [ABSTRACT FROM AUTHOR]

Antibacterial photocatalytic therapy (APCT) is one of the most promising non‐antibiotic treatment strategies for biofilm‐infected wounds and inflammation caused by drug‐resistant bacteria. However, it still faces issues such as inadequate single antibacterial capacity and lack of antioxidant capacity. In this study, a Z‐scheme heterojunction (Bi2S3‐X@PDA) is designed using a polydopamine (PDA) shell firmly anchored to the surface of sulfur vacancy‐rich bismuth sulfide nanorods (Bi2S3‐X NRs). Under near‐infrared light and hydrogen peroxide, Bi2S3‐X@PDA significantly improves the photocatalytic efficiency of reactive oxygen species generation and shows a nearly 100% broad‐spectrum antibacterial effect against multiple bacterial strains and bacterial biofilms in vitro. Interestingly, the antioxidant activity of the PDA shell in Bi2S3‐X@PDA remarkably downregulates the expression of pro‐inflammatory factors and promotes macrophage reprogramming toward the proregenerative M2 phenotype. In a mouse wound model of methicillin‐resistant Staphylococcus aureus biofilm infection, Bi2S3‐X@PDA effectively eliminates drug‐resistant bacterial biofilms through APCT/mild photothermal therapy, while reducing inflammation in normal tissues and regulating the immune microenvironment, thereby promoting rapid wound healing. Overall, this light‐controlled treatment strategy, which provides both antibacterial and anti‐inflammatory functions, is a reliable tool for combating biofilm infection and inflammation caused by drug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan‐based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti‐inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post‐MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation‐targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment. [ABSTRACT FROM AUTHOR]

Methicillin‐resistant Staphylococcus aureus (MRSA) biofilm infection, caused by impaired glucose metabolism in diabetic foot patients, poses a significant obstacle to the healing process and carries a high risk of being life‐threatening. Due to microvascular occlusion and the entrenchment of MRSA biofilms in diabetic foot, controlling and effectively treating MRSA infection remains challenging. Traditional hydrogels suffer from swelling‐related mechanical issues and inadequate drug release control, limiting their applications as biomimetic extracellular matrices for wound healing. Herein, a double‐network hydrogel composed of polyvinyl alcohol, sodium alginate, and gelatin (PSG) loaded with tea polyphenol self‐assembled magnesium nanoparticles (TP‐Mg NPs) with antibacterial and angiogenic properties for treating MRSA‐infected diabetic foot wounds under hyperglycemic conditions is constructed. TP‐Mg@PSG exhibits enhanced mechanical strength and toughness for wound attachment and recovery movement torsion. In the acidic infection microenvironment representative of MRSA‐infected wounds, the TP‐Mg@PSG hydrogel degrades to release TP‐Mg NPs, showing excellent anti‐MRSA biofilm effect and high biocompatibility. Such localized controlled release enhances the inhibition of MRSA infection and reduces the inflammatory response in rats, promoting cell proliferation and rapid wound repair. Therefore, this study presents a multifunctional biomaterial system for managing diabetic foot conditions, highlighting its potential for clinical applications. [ABSTRACT FROM AUTHOR]

Micro/nano drug delivery systems can provide ideal controlled drug release. Microfluidic chip technology plays an important role in the preparation of microspheres. Sodium alginate (SA) has been used to prepare microspheres as drug carriers owing to its good biosafety and easy preparation. However, these microspheres lack antimicrobial activity and drug loading efficiency, which prevent their application for infected wound repair. Although silver nanoparticles (AgNPs) possess broad-spectrum antibiotic activity, liquid mixtures of AgNPs and SA are too unstable to fabricate drug-loaded microspheres using microfluidic chip technology. In this study, AgNPs were coated with silk fibroin (SF) and then dispersed in SA solution to fabricate antibacterial microspheres (denoted SA-SF-Ag) using microfluidic chip technology. SA-SF-Ag effectively inhibited the growth of microorganisms and gradually released AgNPs. Moreover, in vivo results showed that SA-SF-Ag promoted infected wound healing and angiogenesis by killing Pseudomonas aeruginosa on the surface of infected skin wounds of mouse models. This study offers a new method to integrate AgNPs into organic polymeric microspheres for the treatment of infected wounds. [ABSTRACT FROM AUTHOR]

The traditional Chinese herb hawthorn is gaining attention for its potential to lower lipid levels due to its active components that positively influence lipid metabolism. Our meta-analysis of fourteen randomized controlled trials compared traditional Chinese medicine containing hawthorn with conventional lipid-lowering drugs for hyperlipidemia. Hawthorn-based medicine showed promise in reducing total cholesterol and triglycerides while increasing high-density lipoprotein cholesterol levels, albeit less effective than standard drugs in lowering low-density lipoprotein cholesterol. However, caution is needed due to methodological limitations in some trials, emphasizing the importance of further well-designed studies to clarify hawthorn's efficacy in managing hyperlipidemia. [ABSTRACT FROM AUTHOR]

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection. [ABSTRACT FROM AUTHOR]

With the incidence of neurodevelopmental disorders on the rise, it is imperative to screen and evaluate developmental neurotoxicity (DNT) compounds from a large number of environmental chemicals and understand their mechanisms. In this study, DNT qualitative structure-activity relationship (QSAR) study was carried out for the first time based on DNT data of mammals and structural characterization of DNT compounds was preliminarily illustrated. Five different classification algorithms and two feature selection methods were used to construct prediction models. The best model had good predictive ability on the external test set, but a small application domain (AD). Through combining of three different models, both MCC and AD values were improved. Furthermore, electronical properties, van der Waals volume-related properties and S, Cl or P containing substructure were found to be associated with DNT through modeling descriptors analysis and structure alerts (SAs) identification. This study lays a foundation for further DNT prediction of environmental exposures in human and contributes to the understanding of DNT mechanism. Graphical Abstract [ABSTRACT FROM AUTHOR]

Despite the tremendous progress in cancer treatment in recent decades, cancers often become resistant due to multiple mechanisms, such as intrinsic or acquired multidrug resistance, which leads to unsatisfactory treatment effects or accompanying metastasis and recurrence, ultimately to treatment failure. With a deeper understanding of the molecular mechanisms of tumors, researchers have realized that treatment designs targeting tumor resistance mechanisms would be a promising strategy to break the therapeutic deadlock. Nanodelivery systems have excellent physicochemical properties, including highly efficient tissue‐specific delivery, substantial specific surface area, and controllable surface chemistry, which endow nanodelivery systems with capabilities such as precise targeting, deep penetration, responsive drug release, multidrug codelivery, and multimodal synergy, which are currently widely used in biomedical researches and bring a new dawn for overcoming cancer resistance. Based on the mechanisms of tumor therapeutic resistance, this review summarizes the research progress of nanodelivery systems for overcoming tumor resistance to improve therapeutic efficacy in recent years and offers prospects and challenges of the application of nanodelivery systems for overcoming cancer resistance. [ABSTRACT FROM AUTHOR]

Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L‐lactide)‐poly (ethylene glycol)‐ poly (D, L‐lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol‐gel transition in situ. Res has a strong anti‐inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects. [ABSTRACT FROM AUTHOR]

Selenium (Se) and vitamin B2 (VitB2) all play essential roles in participating in hepatic lipid metabolism regulation. In this study, we aimed to identify whether Se combined with VitB2 could meliorate nonalcoholic fatty liver disease (NAFLD) caused by high‐fat (HF) diet in rats. To this end, 50 SD male rats were randomly allotted into five groups equally after receiving a HF diet for 2 weeks. Rats were fed high‐fat diets and gavaged daily with 0.83 or 8.33 µg kg–1 Se combined with 0.70 or 3.50 mg kg–1 VitB2 for 8 weeks. Another 10 rats were given a conventional diet as a control group. The result showed that Se combined with VitB2 decreased NAFLD activity score and liver lipid's levels, relieved hepatic steatosis and lipid deposition and promoted the balance of ApoA1/ApoB ratio. The hepatic 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase (HMGR) level was declined, and the serum HL level was increased in NAFLD rats through the combined intervention. In addition, Se and VitB2 regulated hepatic metabolism factor's (FAS, ACC, ACAT1, PPARγ, and SREBP‐1c) expression level. Taken together, the combined intervention of Se and VitB2 can alleviate HF‐diet‐induced NAFLD in rats. The molecular mechanism may be related to affecting the activities of lipid metabolic enzymes such as FAS, ACC, HMGR, ACAT1, and HL by inhibiting the expression of PPARγ and SREBP‐1c. Practical Applications: The present study showed that a combination of Se and VitB2 can effectively reduce hepatic lipid accumulations, exert hepatoprotective effects and regulate hepatic lipid metabolism in NAFLD rats caused by a high‐fat diet. The possible molecular mechanism may be related to affecting the activities of lipid metabolic enzymes such as FAS, ACC, HMGR, ACAT1, and HL, and inhibiting the expression of PPARγ and SREBP‐1c. Se and VitB2 cosupplementation may be a potential therapeutic strategy in overcoming hepatic lipid disorders' adverse effects beyond pharmacological interventions to ameliorate NAFLD. [ABSTRACT FROM AUTHOR]

Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first‐line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti‐tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications. [ABSTRACT FROM AUTHOR]

The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone‐regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue‐engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies. [ABSTRACT FROM AUTHOR]

The hypoxic tumor microenvironment (TME) significantly affects cancer treatment. Conventional chemotherapeutic agents cannot effectively target hypoxic tumor tissue, which decreases efficacy and results in severe toxic side effects. To alleviate this problem, a self‐driving biomotor is developed by functionalizing MCDP nanoparticles containing calcium peroxide and doxorubicin (DOX) loaded onto polydopamine‐coated metal–organic frameworks（MOF）, with the anaerobic Bifidobacterium infantis (Bif) for synergistic chemotherapy and chemodynamic therapy (CDT) against breast cancer. The materials of institute Lavoisier (MIL) frameworks + CaO2 + DOX + polydopamine (MCDP)@Bif biohybrid actively targets hypoxic regions of solid tumors via the inherent targeting ability of Bif. Once it has accumulated in the tumor tissue, MCDP generates hydroxyl radicals through the enhanced Fenton‐type reactions between Fe2+ and self‐generated hydrogen peroxide in the acidic TME. The disruption of Ca2+ homeostasis and resulting mitochondrial Ca2+ overload triggers apoptosis and enhances oxidative stress, promoting tumor cell death. The results found that the DOX concentration in MCDP@Bif‐treated tumors is 3.8 times higher than that in free‐DOX‐treated tumors, which significantly prolongs the median survival of the tumor‐bearing mice to 69 days and reduces the toxic side effects of DOX. Therefore, the novel bacteria‐driven drug delivery system is highly effective in achieving synergistic chemotherapy and CDT against solid tumors. [ABSTRACT FROM AUTHOR]

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer's disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and β-hydroxybutyrate (β-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aβ), amyloid precursor protein (APP), β-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aβ. [ABSTRACT FROM AUTHOR]

In the case of non-independent and identically distributed samples, we propose a new ueMC algorithm based on uniformly ergodic Markov samples, and study the generalization ability, the learning rate and convergence of the algorithm. We develop the ueMC algorithm to generate samples from given datasets, and present the numerical results for benchmark datasets. The numerical simulation shows that the logistic regression model with Markov sampling has better generalization ability on large training samples, and its performance is also better than that of classical machine learning algorithms, such as random forest and Adaboost. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a promising therapy for refractory cancer based on the cytotoxic reaction of 10B (n, α) 7Li. Although two BNCT agents are clinically available, they are quickly metabolized and show modest enrichment in tumor sites, partially limiting BNCT widespread application. Consequently, novel agents that perform active targeting and show good biocompatibility have to be developed. Herein, boronophenylalanine‐containing polydopamine (B‐PDA) nanoparticles are easily fabricated by encapsulating boronophenylalanine (BPA) in polydopamine via nitrogen‐boronate coordination. In this study, B‐PDA achieves increased tumor accumulation and prolonged retention effects in the tumor site and superior antitumor activity post neutron irradiation in the orthotopic xenograft glioma model. In brief, this study offers a novel strategy for BPA delivery and may broaden the perspective on nanomedicine design for BNCT. [ABSTRACT FROM AUTHOR]

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll‐like receptor agonists delivery system CPG@Au NRs/m‐R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m‐R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m‐R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor‐associated macrophage polarization, triggering DCs maturation and inducing ICD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. Methods: One hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 ± 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. Results: Complete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P =.026) and multivariate (OR 1.11, P =.021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P =.007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P <.1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. Conclusions: AE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response. [ABSTRACT FROM AUTHOR]

Burn wound infections cause serious problems for public health. More than 180,000 patients die from burns every year worldwide. In addition, the difficulty of healing wounds and wound infections caused by burns affects the mental health of patients. Therefore, it is very important to develop a wound dressing that can promote wound repair and exhibits good antibacterial effects. Here, we used oxidized konjac glucomannan (OKGM), γ-poly(glutamic acid) modified with dopamine and L-cysteine (γ-PGA-DA-Cys) and ε-polylysine (ε-PL) to produce an OKGM/γ-PGA-DA-Cys/ε-PL (OKPP) hydrogel. This hydrogel was produced by thiol-aldehyde addition and Schiff-base reactions and has the ability to be injected and self-heal. The results showed that the hydrogel exhibits good antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus and has antioxidant effects in vitro. Moreover, the hydrogel also exhibits good adhesion. In a burn wound infection model, the hydrogel promoted wound healing and reduced the production of inflammation. These results proved that the hydrogel has clinical potential as a wound dressing for burn wound infection. In this study, we prepared OKPP hydrogel constructed from, OKGM, ε-PL, and γ-PGA modified by dopamine and l-cysteine. OKPP hydrogel has the ability of injectable and self-healing through the thiol-aldehyde addition and schiff-base reactions, which can solve the problem of long time use and gel breaking. OKPP hydrogel has antioxidant properties and can scavenge free radicals. This hydrogel has good antibacterial effect on Pseudomonas aeruginosa and Staphylococcus aureus, and also has strong adhesion. In the burn wound infection model, OKPP hydrogel can promote wound healing and reduce the production of inflammatory factors. It is proved that this hydrogel has good clinical potential as a wound dressing for burn wound infection. [ABSTRACT FROM AUTHOR]

As emerging pollutants, direct and indirect adverse impacts of micro(nano)plastics (MPs/NPs) are raising an increasing environmental concern in recent years due to their poor biodegradability and difficulty in recycling. MPs/NPs can act as carriers of bacteria, viruses, or pollutants (such as heavy metals and toxic organic compounds), and may potentially change the toxicity and bioavailability of pollutants. Ingested or attached MPs/NPs can also be transferred from low-trophic level organisms to high-nutrient organisms or even the human body through the food chain transfer process. This article reviews the emerging field of micro- and nanoplastics on organisms, including the separate toxicity and toxicity of compound after the adsorption of organic pollutants or heavy metals, as well as possible mechanism of toxicological effects and evaluate the nano- and microplastics potential adverse effects on human health. The inherent toxic effects MPs/NPs mainly include the following: physical injury, growth performance decrease and behavioral alteration, lipid metabolic disorder, induced gut microbiota dysbiosis and disruption of the gut's epithelial permeability, neurotoxicity, damage of reproductive system and offspring, oxidative stress, immunotoxicity, etc. Additionally, MPs/NPs may release harmful plastic additives and toxic monomers such as bisphenol A, phthalates, and toluene diisocyanate. The vectors' effect also points out the potential interaction of MPs/NPs with pollutants such as heavy metals, polycyclic aromatic hydrocarbons, organochlorine pesticides, polychlorinated biphenyls, perfluorinated compounds, pharmaceuticals, and polybrominated diphenyl ethers. Nevertheless, these potential consequences of MPs/NPs being vectors for contaminants are controversial. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second‐ranking malignancy in hematological tumors. The pathogenesis of MM is complex with high heterogeneity, and the development of the disease is a multistep process. Chromosomal translocations, aneuploidy, genetic mutations, and epigenetic aberrations are essential in disease initiation and progression. The correlation between MM cells and the bone marrow microenvironment is associated with the survival, progression, migration, and drug resistance of MM cells. In recent decades, there has been a significant change in the paradigm for the management of MM. With the development of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, chimeric antigen receptor T‐cell therapies, and novel agents, the survival of MM patients has been significantly improved. In addition, nanotechnology acts as both a nanocarrier and a treatment tool for MM. The properties and responsive conditions of nanomedicine can be tailored to reach different goals. Nanomedicine with a precise targeting property has offered great potential for drug delivery and assisted in tumor immunotherapy. In this review, we summarize the pathogenesis and current treatment options of MM, then overview recent advances in nanomedicine‐based systems, aiming to provide more insights into the treatment of MM. [ABSTRACT FROM AUTHOR]

Peptide‐drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5‐dihydroxybenzoic acid), a non‐steroidal anti‐inflammatory drug (i.e., ibuprofen, IPF), and a self‐assembled peptide motif (i.e., Gly‐Phe‐Phe‐Tyr‐Asp, GFFYD) are integrated to produce a peptide‐drug amphiphile, which self‐assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide‐activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL‐1β, IL‐6 and tumor necrosis factor‐α (i.e., TNF‐α)) compared with that of native IPF via the inhibition of nuclear factor‐κB (i.e., NF‐κB), janus kinase‐signal transducer and activator of transcription (i.e., JAK‐STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti‐inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch pacing (LBBP) is a new near‐physiological pacing modality. Distinguishing left ventricular septal only pacing (LVSP) from nonselective LBBP still needs clarification. This prospective study sought to establish a differentiation algorithm to confirm LBBP. Methods and Results: LBBP was attempted in consecutive patients. If direct LBB capture (LBBP) could not be confirmed, LVSP was considered to have been achieved. Intracardiac left ventricular (LV) activation sequence and activation time were analyzed using coronary sinus (CS) electrogram mapping. Electrophysiological parameters including S‐CSmax, S‐CSmin, LV lateral wall activation time, ΔLV, and LBB potential were compared between LBBP and LVSP. Stimulated LV activation time (S‐LVAT) and stimulated QRS duration (S‐QRSd) were also compared between the two groups. Multivariate logistic regression analysis was used to develop a prediction algorithm for LBBP. Of the 43 prospectively enrolled patients, 27 underwent LBBP and 16 underwent LVSP. All LBBP patients showed identical LV activation sequences to their intrinsic rhythm while no LVSP patients maintained their intrinsic sequence. S‐CSmax, ΔLV, LV lateral wall activation time, and S‐LVAT during LBBP were significantly shorter than those during LVSP. Combining LBB potential with S‐LVAT had the largest area under the curve (AUC) of 0.985 for confirming LBBP with a sensitivity of 95.2% and a specificity of 93.7%. Conclusions: Compared with LVSP, LBBP preserves a normal LV activation sequence and better electrical synchrony. A combination of LBB potential with S‐LVAT can be an effective and practical model to distinguish LBBP from LVSP during implantation in patients with normal LBB activation. [ABSTRACT FROM AUTHOR]

The immunosuppressive tumor microenvironment (TME) is crucial in the occurrence of tumorigenesis, metastasis, and drug resistance. Among all stromal cells, tumor-associated macrophages (TAMs) are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer immunotherapy. To date, nanoparticle (NP)-based drug delivery systems, as new technology platforms, have exhibited considerable advantages, such as targeted drug delivery at tumor sites, enhanced drug transport efficiency, and controllable drug release profiles, which provide new approaches for cancer therapy. Regarding TAM-targeting nanoparticles, various therapeutic strategies have been developed by varying their design, namely, by blocking TAM recruitment, promoting TAM transformation, and directly diminishing existing TAMs. In the current review, we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM targeting. Moreover, the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized. [ABSTRACT FROM AUTHOR]

Focal therapy, or partial gland ablation, represents the middle ground between active surveillance and definitive treatment strategies against localized prostate cancer (PCa), among which the ultrasound‐ and light‐mediated focal therapies are quite promising. Herein, for the first time in the literature, a novel polysaccharide‐based nanoprodrug is fabricated for synergistic sonodynamic therapy and phototherapy against localized PCa. Specifically, the cyanine dye IR806 is conjugated to chondroitin sulfate (CS) via disulfide linkages to obtain CS‐ss‐IR806 (CSR) conjugates, which then self‐assemble to form CSR nanoparticles (NPs) with properties of enhanced endocytosis, redox/hyaluronidase‐responsiveness, and mitochondria‐targeted ability. In contrast to free sensitizers, CSR NPs reveal dramatically enhanced water solubility, substantially lower dark toxicity, and superior biocompatibility. Encouragingly, favorable hyperthermia and high reactive oxygen species generation are observed on exposing CSR NPs to combined sono/photoirradiation. In a PCa tumor‐bearing mice model, intratumoral injection with a markedly low dose of CSR NPs followed by dual‐irradiation results in superior trimodal anticancer efficacy when compared with either monoirradiation strategy. Such synergistic antitumor efficacy is further demonstrated to be associated with the common and complementary mechanisms of sonotherapy and phototherapy. This work provides a promising approach as a next‐generation focal therapy strategy against localized PCa. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the therapeutic outcomes of cancer chemotherapy. Docetaxel (DTX) is used for breast cancer treatment and has gastrointestinal side effects, but the influence of DTX formulations on the intestinal barrier and intestinal microbiota remains unknown. Therefore, in this work, the influence of DTX injection (free DTX, commercial formulation) and DTX/methoxy poly(ethylene glycol)‐block‐poly(D,L‐lactide) (mPEG‐PDLLA) (DTX micelles, nanoformulation) on the integrity of the intestinal barrier and the intestinal microbiota is investigated. It is found that the free DTX causes significantly greater intestinal barrier damage than the DTX micelles. The diversity of the intestinal microbiota, and the relative abundance of Akkermansia muciniphila and Ruminococcus gnavus in the DTX micelle‐treated group is significantly higher than that in the free DTX‐treated group. Moreover, the tumor growth rate is elevated in antibiotic mixture‐pretreated mice, demonstrating that the diversity and composition of the intestinal microbiota may be associated with tumor progression. This work demonstrates that different formulations of chemotherapeutics have different effects on the integrity of the intestinal barrier and the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Aims Myocardial fibrosis is associated with clinical ventricular tachyarrhythmia (VTA) events in patients with non-ischaemic dilated cardiomyopathy (DCM). Subepicardial or mid-wall ring-like late gadolinium enhancement (LGE) has received increasing attention in recent years. The aim of this study was to investigate the relationship between ring-like LGE and VTAs in DCM. Methods and results Patients diagnosed with non-ischaemic DCM who underwent cardiac magnetic resonance with LGE imaging at baseline were investigated. The composite outcome was the occurrence of VTAs defined as sustained ventricular tachycardia, ventricular fibrillation/flutter, aborted sudden cardiac death (SCD), SCD, and appropriate implantable cardioverter-defibrillator intervention. The final cohort comprised 157 patients, including 36 (22.9%) in no LGE group, 48 (30.6%) in focal LGE group, 40 (25.5%) in multi-focal LGE group, and 33 (21%) in ring-like LGE group. Ring-like LGE group patients were younger compared to focal and multi-focal LGE group (P  <   0.001) with higher left ventricular ejection fraction (33.0% vs. 24.4% vs. 22.1%, P  <   0.001). After a median of 13 ± 7 months follow-up, compared to patients with no LGE, the hazard ratios (HRs) with 95% confidence intervals (CIs) for VTAs were 2.90 (0.56–15.06), 5.55 (1.21–25.44), and 11.75 (2.66–51.92) for patients with focal LGE, multi-focal LGE, and ring-like LGE, respectively. After multivariable adjustment, ring-like LGE group remained associated with increased risk of VTAs (adjusted HR 10.00, 95% CI 1.54–64.98; P  =   0.016) independent of the global LGE burden Conclusion The ring-like pattern of LGE is independently associated with an increased risk of VTAs in patients with non-ischaemic DCM. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch (LBB) pacing has emerged as a novel pacing modality. Left ventricular activation time (LVAT) was reported to be associated with the activation via LBB, but the value of LVAT for determining LBB pacing was unknown. We conducted a pilot study to determine if LVAT could define LBB capture by validating left ventricular (LV) mechanical synchrony. Methods: We analyzed LVAT in 68 bradycardia-indicated patients who received LBB pacing. LVAT was measured from the stimulus to R-wave peak in lead V5 and V6. LV mechanical synchrony assessed by SPECT MPI was compared according to the value of LVAT and the presence of LBB potential. Results: The mean LVAT was 75.4 ± 12.7 ms. LBB potential was recorded in 47 patients (69.1%). Patients with LVAT < 76 ms had better LV mechanical synchrony than those with LVAT ≥ 76 ms. Patients with LVAT < 76 ms or LBB potential had better mechanical synchrony than those with LVAT ≥ 76 ms and no potential. LVAT < 76 ms could predict the normal synchrony with a sensitivity of 88.9% and a specificity of 87.5%. Conclusion: A short LVAT indicated favorable mechanical synchrony in SPECT imaging. LVAT < 76 ms might be a practical parameter for defining LBB capture. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in humans. The inhibition of peptidyl‐prolyl cis/trans isomerase (Pin1) gene expression may have great potential in the treatment of HCC. N‐Acetylgalactosamine (GalNAc) was used to target the liver. Cholesterol‐modified antimicrobial peptide DP7 (DP7‐C) acts as a carrier, the GalNAc‐siRNA/DP7‐C complex increases the uptake of GalNAc‐siRNA and the escape of endosomes in hepatocytes. In addition, DP7‐C nanoparticles and hydrogel‐assisted GalNAc‐Pin1 siRNA delivery can effectively enhance the stability and prolong the silencing effects of Pin1 siRNA. In an orthotopic liver cancer model, the GalNAc‐Pin1 siRNA/DP7‐C/hydrogel complex can potentially regulate Pin1 expression in hepatocellular carcinoma cells and effectively inhibit tumor progression. Our study proves that Pin1 siRNA is an efficient method for the treatment of HCC and provides a sustainable and effective drug delivery system for the suppression of liver cancer. [ABSTRACT FROM AUTHOR]

Background: Several studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT.Methods: We searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV).Results: The study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47]; p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92]; p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, - 12.46 [95% CI, - 18.89 to - 6.03]; p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70]; p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08]; p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29]; p = 0.24, respectively).Conclusions: This meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate. [ABSTRACT FROM AUTHOR]

The interaction of nanoparticles (NPs) with proteins and the formation of protein corona in the biological fluids are of great interest and significance for drug delivery. In the past decade, the corona formation in the blood and its impacts on the in vitro and in vivo fate of NPs has been well investigated and reviewed. Recently, more and more attention is paid to the nano–protein interactions taking place in the gastrointestinal tract (GIT) between the orally administered NPs and the digestive enzymes. The enzyme corona formed in the GIT can significantly affect the properties, gastrointestinal transit, and oral absorption of NPs. Since oral delivery is the most preferred delivery route, comprehensively understanding the corona formation in the GIT and its impacts on oral delivery NPs are of great importance. Herein, we aim to summarize the recent updates on the nano–protein interactions between NPs and digestive enzymes, and launch an interesting discussion on the potentials of using the digestive enzyme corona for the colon targeted delivery. [ABSTRACT FROM AUTHOR]

The diagnosis of malignant tumors is essential for informing clinical decisions regarding therapeutic options. Current imaging and pathological diagnostic methods do not provide quantitative molecular information that is important in tumor identification. Moreover, pathological tissue analysis is dependent on unevenly distributed pathological features. The tumor microenvironment has been documented to have hydrogen peroxide (H2O2). This study presents a biologically sensitive and efficient H2O2 electrochemical sensor based on PtNi nanoparticle‐doped N‐reduced graphene oxide (PtNi‐N‐rGO) with a low detection limit (2.8 × 10–9m), a fast response time (<6 s) and desirable anti‐interference characteristics. Herein, H2O2 is used as molecular biomarker. The sensor successfully captures H2O2 from cancer cells. In addition, it efficiently detects tumor tissues, adjacent tissues, and normal tissues. This study demonstrates the H2O2 sensor potential to rapidly detect tumor tissues. This technique provides a complementary method for pathological tumor diagnosis that is independent of the traditional pathology labs. [ABSTRACT FROM AUTHOR]

Acquired chemoresistance presents a major clinical impediment, which is an urgent problem to be solved. Interestingly, myeloma cell leukemia‐1 (MCL‐1) and folate receptor expression levels are higher in chemotherapy‐resistant patients than in pretreatment patients. In this study, a multifunctional folic acid (FA)‐targeting core–shell structure is presented for simultaneous delivery of shMCL‐1 and paclitaxel (PTX). The transfection efficiency of shMCL‐1 with the FA‐targeting delivery system is higher than with a nontargeting delivery system in Skov3 and A2780T cells. The FA‐targeting system significantly inhibits cell growth, blocks cell cycles, and promotes apoptosis of cancer cells in vitro. The mechanisms involved in inhibiting growth are related to Bcl‐2/Bax and cdc2/Cyclin B1 pathways. An analysis of RNA sequencing suggests that shMCL‐1 reverses chemoresistance through regulating genes such as regulator of chromosome condensation 2 (RCC2). The synergetic effect of shMCL‐1 and PTX effectively inhibits tumor growth in both PTX‐resistant and normal cancer models by inducing tumor apoptosis, inhibiting proliferation, and limiting tumor angiogenesis. The study results indicate that a FA‐targeting delivery system combining shMCL‐1 with PTX can simultaneously target tumor sites and restore the sensitivity of chemotherapy‐resistant cancer to PTX. These findings have important implications for patients with normal or PTX‐resistant cancer. [ABSTRACT FROM AUTHOR]

Background. The study was aimed at exploring the electrophysiological characteristics (EPS) of the optimal ablation site and its relationship with electroanatomic voltage mapping (EVM) in idiopathic premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT). Methods. A total of 28 patients with idiopathic RVOT PVCs underwent successful ablation and EVM using a 3D electroanatomical mapping (CARTO) system. Results. Both bipolar and unipolar EVM showed a similar band-like lower-voltage area (LVA) under the pulmonary valve in all the patients; 21.4% of the targets were located in the band-like LVA. 42.9% of the targets were at the border of the band-like LVA on the bipolar voltage map, but unipolar mapping showed that 53.6% of the targets were located in the band-like LVA, and 35.7% of the targets at the border of the band-like LVA. A significant difference was found in both unipolar and bipolar voltage values between the regions within 0-5 mm above the optimal ablation site and the other regions. A similar difference was observed only in unipolar voltage values below the optimal ablation site. At the ablation site, there were frequent occurrences of a fragmented wave and voltage reversion in the bipolar electrograms, frustrated falling limbs, W bottom, and a QS configuration width > 150 ms in the unipolar electrograms. Conclusions. EVM showed that the band-like LVA was an interesting area for the search of the optimal ablation sites of idiopathic RVOT-PVCs, especially the border area. There was focal microscarring around the ablation targets; some characteristics of EPS proved significant for successful ablation. [ABSTRACT FROM AUTHOR]

Objectives: Using ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), we sought to develop and validate a new method to recommend left ventricular (LV) lead positions in order to improve volumetric response and long-term prognosis after cardiac resynchronization therapy (CRT).Methods: Seventy-nine patients received gated SPECT MPI at baseline, and echocardiography at baseline and follow-up. The volumetric response referred to a reduction of ≥ 15% in LV end-systolic volume 6 months after CRT. After excluding apical, septal, and scarred segments, there were three levels of recommended segments: (1) the optimal recommendation: the latest contracting viable segment; (2) the 2nd recommendation: the late contracting viable segments whose contraction delays were within 10° of the optimal recommendation; and (3) the 3rd recommendation: the viable segments adjacent to the optimal recommendation when there was no late contracting viable segment.Results: After excluding 11 patients whose LV lead was placed in apical or scarred segments, 75.6% of the patients concordant to recommended LV segments (n = 41) responded to CRT while 51.9% of those with non-recommended LV lead locations (n = 27) were responders (P = .043). Response rates were 76.9%, 76.9% , and 73.3% (P = .967), respectively, when LV lead was implanted in the optimal recommendation (n = 13), the 2nd recommendation (n = 13), and the 3rd recommendation (n = 15). LV leads placed at recommended segments reduced composite events of all-cause mortality or heart failure (HF) rehospitalization compared with pacing at non-recommended segments (log-rank χ2 = 5.623, P = .018).Conclusions: Pacing in the recommended LV lead segments identified on gated SPECT MPI was associated with improved volumetric response to CRT and long-term prognosis. [ABSTRACT FROM AUTHOR]