IntroductionNanozymes have emerged as promising substitutes for natural enzymes in chemiluminescent immunoassays, offering distinct catalytic advantages and superior stability. Despite their potential, many conventional nanozymes are constrained by a strong dependence on pH, which limits their effectiveness in certain assay environments. This highlights the need for nanozymes that maintain robust catalytic activity under alkaline conditions and are compatible with luminol-based detection systems.MethodsIn this study, we synthesized platinum nanoparticle-modified Prussian blue cubes (PB@Pt) and evaluated their enzyme-mimicking activity. The catalytic performance of PB@Pt was assessed under both weakly acidic and alkaline conditions. Its ability to enhance the luminol-H2O2 chemiluminescence (CL) system was investigated, and the CL signals were compared to those generated by natural horseradish peroxidase (HRP). Based on these properties, a novel CL immunoassay utilizing PB@Pt was developed for the sensitive detection of vascular endothelial growth factor (VEGF).Results and DiscussionThe synthesized PB@Pt exhibited high catalase (CAT)-like activity across a broad pH range, including alkaline media. Remarkably, in alkaline conditions, PB@Pt catalyzed the luminol-H2O2 reaction, producing CL signals significantly stronger than those achieved with natural HRP. Leveraging this enhanced performance, the established PB@Pt-based CL immunoassay enabled a wide linear detection range, ultra-low detection limits, high specificity, and excellent stability for VEGF quantification. This work introduces a novel strategy for designing CAT-mimicking nanozyme probes, thereby broadening their utility in CL immunoassays and advancing the clinical translation of nanozyme-based diagnostics for applications such as biomarker screening and point-of-care testing (POCT).

Highly efficient detection and sterilization techniques for bioaerosol prevention and control are urgently needed. Herein, we present an AIE-active Janus air filter membrane (AIE-HAFM) that features water-dissolvable micro-nano porous network architecture and aggregation-induced emission (AIE) activity constructed by the asymmetrical surface modification with an amphiphilic AIE photosensitizer (MeOTTVP). The all-round AIE-HAFM can not only provide low pressure drop and high interception efficiency for bioaerosol sampling but also perfectly inherit the AIE functions of MeOTTVP, which allows for intensive near-infrared (NIR) emission and efficient production of reactive oxygen species. The airborne pathogens can be effectively captured, collected, transferred, and released by AIE-HAFM for subsequent quantitative detection with colony counting and ATP bioluminescence, as well as stained by the incorporated MeOTTVP for NIR fluorescence imaging-guided visual detection. Meanwhile, AIE-HAFM enables on-demand and surface-dependent photodynamic effects for reliable bacterial eradication under white light irradiation due to the surface-concentrated MeOTTVP, consequently achieving the smart prevention and control of bioaerosols both in the simulated and real-world bioaerosol environment. The versatility of AIE-HAFM in handling diverse airborne pathogens may bring about a transformative solution to address the bioaerosol contamination problems.

Mulberry (Morus nigra L.) is traditionally recognized for its bone-strengthening properties, yet its active constituents and underlying mechanisms remain incompletely understood. This study investigates the effects of maclurin, a key flavonoid from mulberry, on extracellular matrix (ECM) deposition and bone formation. In vitro, maclurin (5-20 μM) treatment enhanced ECM protein expression, including fibronectin (FN), laminin subunit gamma-2, and collagen alpha-1(I) chain (Col I) in MC3T3-E1 osteoblasts in a dose-dependent manner. Transcriptomic analysis suggested the involvement of PI3K/Akt signalling pathway, which was subsequently validated by increased Akt phosphorylation that was reversed by siAkt and PI3K inhibitor LY294002. In a subcutaneous ectopic bone formation model, oral maclurin administration (0.5-2.0 mg/kg) promoted Col I and FN expressions, improved collagen fibre organization, and increased calcium deposition in newly formed bone tissues. These results provide experimental evidence for osteogenic activity of maclurin and enhance our understanding of the bone-health benefits associated with mulberry.

Cell-culture room provides an interference-free clean environment for sterilized experimental operation and pharmaceutical production with high standards. However, the recurrent bioaerosol contamination poses a serious threat to its normal operation. Trapping by the low concentration of airborne microbes in such clean rooms, the sampling and characterization of bioaerosol contamination are appealing yet significantly challenging tasks. Herein, inspired by the integrative advantages of green dissolvable filter (HAFM), the bioaerosol particles in cell-culture rooms were captured and systematically investigated by cultivated and non-cultivated methods. Benefiting from the higher interception efficiency and superior compatibility than the commonly used sampling strategies, the HAFM-captured bioaerosol samples can optionally perform colony cultivation, counting, microscopic observation, and high-resolution imaging. Importantly, the real composition and abundance of the microbial community in cell-culture rooms can be presented by combining filtered sampling with high-throughput sequencing. The shared bacterial genera of Pseudomonas (44.34 %), Aquabacterium (14.25 %), Dechloromonas (3.17 %), Tepidiphilus (3.02 %), and Fluviicola (2.72 %), and fungal genera of Aspergillus (17.39 %), Cladosporium (12.62 %), Apiotrichum (8.91 %), Epicoccum (6.82 %), and Alternaria (5.02 %), are responsible for the bioaerosol contamination in cell-culture rooms. This work provides a promising avenue to overcome incompetence in accurate bioaerosol detection and identification in clean rooms.

Human epidermal growth factor receptor-2 (HER2) is overexpressed in various solid tumor types, acting as an established therapeutic target. Over the last three decades, the fast-paced development of diverse HER2-targeted agents, notably marked by the introduction of the antibody-drug conjugate (ADC), yielding substantial improvements in survival rates. However, resistance to anti-HER2 treatments continues to pose formidable challenges. The complex structure and dynamic dimerization properties of HER2 create significant hurdles in the development of novel targeted therapeutics. In this review, we synthesize the latest insights into the structural intricacies of HER2 and present an unprecedented overview of the epitope characteristics of HER2-targeted antibodies and their derivatives. Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.

Articular cartilage injuries and osteochondral defects are a significant clinical challenge, as conventional treatments often have limited success. Articular cartilage has limited self-regeneration ability due to the absence of blood vessels, nerves, and lymphatic vessels, making it challenging to repair tissue defects and restore motor function in injured or aging populations. Additionally, the anatomical complexity and slow regeneration capacity of hyaline cartilage at the osteochondral interface pose significant problems in repairing osteochondral defects. Melt electrowriting, a novel technology particularly suitable for polycaprolactone (PCL) is expected to overcome the common limitations of 3D-printed scaffolds, such as poor tissue-porosity matching, low resolution, and inflexible shapes. In recent years, melt electrowriting (MEW) has become a promising strategy for repairing cartilage and osteochondral defects. However, there is still a lack of systematic understanding regarding the comparative characteristics and application value of MEW compared with commonly used 3D printing technologies such as extrusion printing, inkjet printing, and fusion deposition modeling. This review paper compares the characteristics and advantages of MEW and common 3D printing technologies, providing a comprehensive summary of the significant progress and applications of MEW for cartilage/osteochondral repair. Finally, the challenges and key directions for future research in MEW technology will also be discussed. In recent years, melt electrowriting (MEW) has emerged a promising approach for cartilage and osteochondral defect repair. Nevertheless, there remains a dearth of comprehensive comprehension concerning the relative attributes and applicative worth of MEW. This review article delivers an all-encompassing overview of the substantial advancements and applications of MEW in the realm of cartilage and osteochondral restoration.image

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy—a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells’ inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy’s efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT’s efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.

Traditional chemotherapy and immunotherapy are primary disease-treatment strategies. However, they face numerous challenges, including limited therapeutic benefits, off-target effects, serious adverse effects, drug resistance, long half-life time, poor oral bioavailability, and drugging undruggable proteins. Proteolytic targeted chimeras (PROTACs) were suggested to solve these problems. PROTACs are heterogeneous functional molecules linked by a chemical linker and contain a binding ligand for the protein of interest and a recruiting ligand for the E3 ligand. The binding of a PROTAC to a target protein brings the E3 ligand enzyme into proximity, initiating polyubiquitination of the target protein, followed by protease-mediated degradation. To date, PROTACs against dozens of immunological targets have been successfully developed, many of which have been clinically validated drug targets, and several have entered clinical trials for immune-related diseases. This article reviews the role of PROTACs-mediated degradation of critical proteins in immune disorders and cancer immunotherapy. Chemical structures, cellular and in vivo activities, and pharmacodynamics of these PROTACs are summarized. Lastly, we also discuss the prospects and potential limitations that PROTACs face.

Innate lymphoid cells (ILCs) are a recently discovered subset of immune cells that play a crucial role in preserving tissue health and combating infections. Among these, ILC3s are particularly vital in regulating mucosal immunity across multiple organs such as the gut, lungs, and skin. The purpose of this article is to present a comprehensive and detailed overview of current knowledge on ILC3s, with a specific emphasis on their intricate interactions with various components of the intestinal microenvironment. Recent research on the complex, bidirectional communication pathways between ILC3s and intestinal epithelial cells, stromal cells, immune cells, microbiota, their metabolites, and diet are highlighted. Furthermore, this review comprehensively examines the diverse functions of ILC3s, which include lymphoid tissue development, tissue repair, infection, inflammation, and metabolic diseases, as well as the effector molecules that facilitate these functions. Overall, this review provides valuable insights into the biological and functional aspects of ILC3s and underscores their potential for developing innovative therapies for immune-mediated disorders, while also acknowledging the remaining knowledge gaps and challenges that need to be addressed.

Despite the emergence of molecular targeted therapy and immune checkpoint inhibitors as standard first-line treatments for non-small cell lung cancer (NSCLC), their efficacy in some patients is limited by intrinsic and acquired resistance. Antibody-drug conjugates (ADCs), a revolutionary class of antitumor drugs, have displayed promising clinical outcomes in cancer treatment. In 2022, trastuzumab deruxtecan (Enhertu) was approved for treating HER2-mutated NSCLC, thereby underscoring the clinical value of ADCs in NSCLC treatment strategies. An increasing number of ADCs, focusing on NSCLC, are undergoing clinical trials, potentially positioning them as future treatment options. In this review, we encapsulate recent advancements in the clinical research of novel ADCs for treating NSCLC. Subsequently, we discuss the mechanisms of action, clinical efficacy, and associated limitations of these ADCs.

Colorectal cancer (CRC) is the most common malignancy-related cause of death worldwide. The prognosis of CRC patients is strongly correlated with elevated plasma copper. The quantitative detection of plasma copper is highly essential for the field of biomedicine, and our hypothesis was that plasma copper may be a therapeutic target for treating CRC. Here, we developed metformin-based carbon dots (MFCDs). MFCDs have strong photo-luminescence at 460 nm, which is quenched by Cu2+. Cu2+ concentration and the fluorescence emission intensity of MFCDs are significantly associated (linear range of 0.5-40 mu M with a detection limit of 0.30 mu M). Additionally, administration of MFCDs significantly inhibited the growth of CRC xenografts in mice caused by the existence of biguanide functional groups. MFCDs treatment led to the increase of reactive oxygen species and subsequent DNA damage and cell cycle arrest. This study showed that the biguanide functional groups of MFCDs chelate with Cu2+, resulting in the reduction of Cu/Zn-superoxide dismutase and glutathione, which eventually reduces antioxidant capacity and ultimately induces cell apoptosis. These results indicate that MFCDs provide a novel approach for anticancer therapy.

Objectives The aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation. Methods Localized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set ( n = 49), the validation set ( n = 7), and the test set ( n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework. Results With the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples. Conclusions For the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

Trophoblast cell surface antigen 2 (Trop2) exhibits limited expression in normal tissues but is over-expressed across various solid tumors. The effectiveness of anti-Trop2 antibody-drug conjugate (ADC) in managing breast cancer validates Trop2 as a promising therapeutic target for cancer treatment. However, excessive toxicity and a low response rate of ADCs pose ongoing challenges. Safer and more effective strategies should be developed for Trop2-positive cancers. The dynamic structural attributes and the oligomeric assembly of Trop2 present formidable obstacles to the progression of innovative targeted therapeutics. In this review, we summarize recent advancements in understanding Trop2’s structure and provide an overview of the epitope characteristics of Trop2-targeted agents. Furthermore, we discuss the correlation between anti-Trop2 agents’ epitopes and their respective functions, particularly emphasizing their efficacy and specificity in targeted therapies.

Cholesterol levels are an initiating risk factor for atherosclerosis.Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2.Especially, HMGCR, SQLE, FDFT1, LSS, FDPS, CYP51, and EBP are promising therapeutic targets for drug development due to many drugs have been approved and entered into clinical research by targeting these genes.However, new targets and drugs still need to be discovered.Interestingly, many small nucleic acid drugs and vaccines were approved for the market, including Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran.However, these agents are all linear RNA agents.Circular RNAs (circRNAs) may have longer half-lives, higher stability, lower immunogenicity, lower production costs, and higher delivery efficiency than these agents due to their covalently closed structures.CircRNA agents are developed by several companies, including Orna Therapeutics, Laronde, and CirCode, Therorna.Many studies have shown that circRNAs regulate cholesterol synthesis by regulating HMGCR, SQLE, HMGCS1, ACS, YWHAG, PTEN, DHCR24, SREBP-2, and PMK expression.MiRNAs are essential for circRNA-mediated cholesterol biosynthesis.Notable, the phase II trial for inhibiting miR-122 with nucleic acid drugs has been completed.Suppressing HMGCR, SQLE, and miR-122 with circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, and circFOXO3 are the promising therapeutic target for drug development, specifically the circFOXO3.This review focuses on the role and mechanism of the circRNA/miRNA axis in cholesterol synthesis in the hope of providing knowledge to identify new targets.

Phytopharmaceuticals have attracted a lot of attention due to their multicomponent and multiple targets. The natural phenolic chemicals known as flavonoids are found in a wide variety of plants, fruits, vegetables, and herbs. Recently, they have been found to have modulatory effects on anxiety disorders, with current research focusing on the modulation of neurotransmitters. There has not yet been a review of the various natural flavonoid monomer compounds and total plant flavonoids that have been found to have anxiolytic effects. The study on the anti-anxiety effects of plant-derived flavonoids on neurotransmitters was reviewed in this paper. We, therefore, anticipate that further study on the conformational interaction underlying flavonoids' anti-anxiety effects will offer a theoretical framework for the creation of pertinent treatments.

Aims: To develop more potent drugs that eradicate persister bacteria and cure persistent urinary tract infections (rUTIs). Methods and results: We synthesized eight novel clinifloxacin analogs and measured minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), the time-kill curves in uropathogenic Escherichia coli (UPEC) UTI89, and applied the candidate drugs and combinations against biofilm bacteria in vitro and in mice. Transcriptomic analysis was performed for UPEC after candidate drug treatment to shed light on potential mechanism of action. We identified Compound 2, named Qingdafloxacin (QDF), which was more potent than clinafloxacin and clinically used levofloxacin and moxifloxacin, with an MIC of < 0.04 mu g ml(-1) and an MBC of 0.08 similar to 0.16 mu g ml(-1). In drug combination studies, QDF + gentamicin + nitrofuran combination but not single drugs completely eradicated all stationary phase bacteria containing persisters and biofilm bacteria, and all bacteria in a persistent UTI mouse model. Transcriptome analysis revealed that the unique antipersister activity of QDF was associated with downregulation of genes involved in bacterial stress response, DNA repair, protein misfolding repair, pyrimidine metabolism, glutamate, and glutathione metabolism, and efflux. Conclusions: QDF has high antipersister activity and its drug combinations proved highly effective against biofilm bacteria in vitro and persistent UTIs in mice, which may have implications for treating rUTIs.