Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

An evolutionary differential game for regulating the role of monoclonal antibodies in treating signalling pathways in oesophageal cancer.

This work presents a new framework for a competitive evolutionary game between monoclonal antibodies and signalling pathways in oesophageal cancer. The framework is based on a novel dynamical model that takes into account the dynamic progression of signalling pathways, resistance mechanisms and monoclonal antibody therapies. This game involves a scenario in which signalling pathways and monoclonal antibodies are the players competing against each other, where monoclonal antibodies use Brentuximab and Pembrolizumab dosages as strategies to counter the evolutionary resistance strategy implemented by the signalling pathways. Their interactions are described by the dynamical model, which serves as the game's playground. The analysis and computation of two game-theoretic strategies, Stackelberg and Nash equilibria, are conducted within this framework to ascertain the most favourable outcome for the patient. By comparing Stackelberg equilibria with Nash equilibria, numerical experiments show that the Stackelberg equilibria are superior for treating signalling pathways and are critical for the success of monoclonal antibodies in improving oesophageal cancer patient outcomes.

Synergistic anticancer immunity in metastatic triple-negative breast cancer through an in situ amplifying Peptide-Drug Conjugate.

Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvß3 and gets continuously activated by apoptosis. TPD1 facilitates the caspase-3-mediated in situ amplification that results in tumor-specific accumulation of doxorubicin. This local concentration of doxorubicin induces immunogenic cell death and promotes the recruitment of immune cells to the tumor site. Notably, the tumor-targeting capabilities of TPD1 help bypass the systemic immunotoxicity of doxorubicin. Consequently, this alters the tumor microenvironment, converting it into a 'hot' tumor that is more susceptible to immune checkpoint inhibition. We demonstrated the anti-metastatic and anti-cancer efficacy of this treatment using various xenograft and metastatic models. This study underscores the high potential of caspase-3 cleavable peptide-drug conjugates to be used in conjunction with anti-cancer immunotherapies.

Anti-tumor effect of antibody-drug conjugate targeting cell adhesion molecule 1 on GIST cells representing small intestinal GIST.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the alimentary tract. The prognosis depends on the primary site, and small intestinal GISTs have a worse prognosis than gastric GISTs. Molecularly targeted drugs to inhibit tyrosine kinase activity of KIT were used for unresectable or recurrent GISTs. However, secondary resistance to the drugs is often acquired, and treatments based on other mechanisms are needed. Previously, we reported that cell adhesion molecule 1 (CADM1) was highly expressed in most of small intestinal GISTs but not in most of gastric GISTs. In the present study, we examined whether the antibody-drug conjugate (ADC) with anti-CADM1 antibody and monomethyl auristatin E (anti-CAD-ADC) shows anti-tumor effect on CADM1-expressing human GIST cells. The ADC adhibited in this study was previously used for CADM1-expressing human mesothelioma cells and showed anti-tumor effect for them in vitro. GIST-T1 cell line of gastric origin which scarcely expresses CADM1 and GIST-T1 cells transfected with CADM1 cDNA (GIST-T1-CAD cells) which highly expresses CADM1 and represents small intestinal GIST were used. In vitro, anti-CAD-ADC showed remarkable cytotoxic activity on GIST-T1-CAD cells, but control ADC did not. Both anti-CAD-ADC and control ADC did not show anti-tumor effect on original GIST-T1 cells. When GIST-T1-CAD cells were subcutaneously injected to the nude mice, intravenous administration of anti-CAD-ADC showed inhibitory effect for tumor enlargement. Tumor of GIST-T1 cells grew even after anti-CAD-ADC injection. When GIST-T1-CAD cells were injected into peritoneal cavity of the SCID mice, intraperitoneal administration of anti-CAD-ADC showed reduction of the peritoneal tumor. On the other hand, peritoneal tumor grew after control ADC administration. Tissue and organ damage due to administration of anti-CAD-ADC was not apparent by macroscopic and histological examinations in mice. These results indicate that anti-CAD-ADC could have apparent anti-tumor effect on CADM1-expressing human GIST cells both in in vitro and in vivo mouse models.

Glycated nisin enhances nisin's cytotoxic effects on breast cancer cells.

Antimicrobial peptides, such as nisin, are proposed as promising agents for cancer treatment. While glycation has been recognized as an effective method for enhancing various physicochemical properties of nisin, its anticancer effects remain unexplored. Therefore, we aimed to assess the anticancer potential of glycated nisin against MDA-MB-231 cells. The MDA-MB cells were treated with increasing concentrations of nisin and glycated nisin for 24, 48, and 72 h. The IC50 values for nisin were higher than those for glycated nisin. Glycated nisin at concentrations of 20 and 40 µg/mL decreased cell viability more than nisin at the same concentrations. The rate of apoptosis in the group treated with 20 µg/mL of nisin was lower compared to other treatment groups, and no significant difference in apoptosis rates was observed at different time points (p > 0.05). However, in the glycated nisin groups with concentrations of 10, 20, and 40 µg/mL, the level of apoptosis was very high after 24 h (73-81% of cells undergoing apoptosis). Overall, our study suggests that glycated nisin exhibits stronger cytotoxic effects on MDA-MB-231 cells, primarily involving the induction of apoptosis. This indicates its potential utilization as an alternative approach to address the issue of drug resistance in cancer cells.

Serotype distribution of invasive pneumococcal disease from countries of the WHO Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific regions: a systematic literature review from 2010 to 2021.

Background: Most publications on invasive pneumococcal disease (IPD) serotype distribution are from about 20 countries (Australia, Canada, China, European Union members, Japan, New Zealand, South Korea, and USA). Here, we reviewed the literature among underrepresented countries in the Americas (AMRO), Africa (AFRO), Eastern Mediterranean (EMRO), South-East Asia (SEARO), and Western Pacific (WPRO) WHO regions. Methods: We performed a systematic review of the most recent IPD serotype surveillance publications (from 01/01/2010 to 31/12/2021, Medline/Embase) in those WHO regions. Selection criteria were delineated by contemporality, within-country geographical scope, and number of samples. Reported serotype distributions for each country were stratified by age group, pneumococcal conjugate vaccine (PCV) serotype category (considering undifferentiated serotypes), and PCV program period (pre-PCV, intermediate, or PCVhv [higher valency PCV formulation]). Pre-PCV period pooled data estimated PCV serotype category distribution by age group across WHO regions, while for the PCVhv period, country-level dataset tables were prepared. Results: Of 2,793 publications screened, 107 were included (58 pediatric, 11 adult, 37 all ages, and one comprising every age group). One-third of eligible countries (51/135) published serotype distribution, ranging from 30 to 43% by WHO region. Considering number of samples per WHO region, a few countries prevailed: AMRO (Brazil), AFRO (South Africa, Malawi, and Burkina Faso), and WPRO (Taiwan). In the pre-PCV period, PCV13 formulation serotypes predominated: ranging from 74 to 85% in children and 58-86% in adults in the different WHO regions. The PCVhv period represented half of the most recent IPD surveillance by countries (26/51). Undifferentiated serotypes represented >20% of IPD from most countries (34/51). Conclusion: Ubiquity of undifferentiated serotypes among the publications could constrain estimates of PCV program impact and of serotype coverage for newer PCVhv formulations; consequently, we recommend that countries favor techniques that identify serotypes specifically and, rather than reporting PCV formulation serotype distributions, provide serotype results individually. Systematic review registration: The protocol has been prospectively registered at PROSPERO, identifier: CRD42021278501. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278501.

Mechanisms of action and resistance to anti-HER2 antibody-drug conjugates in breast cancer.

Human epidermal growth factor 2 (HER2)-positive breast cancer (BC) represents nearly 20% of all breast tumors. Historically, these patients had a high rate of relapse and dismal prognosis. The advent of HER2-targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. More recently, antibody-drug conjugates (ADCs) are now reshaping the treatment paradigm of solid tumors, especially breast cancer. Tratsuzumab emtansine (T-DM1) was one of the first ADC developed in oncology and was approved for the management of HER2-positive metastatic BC. In a head-to-head comparison, trastuzumab deruxtecan (T-DXd) defeated T-DM1 as a second-line treatment. The efficacy of ADCs is counterbalanced by the appearance of acquired resistance to these agents. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.

An approach for the intracellular delivery of IgG via enzymatic ligation with a cell-permeable attenuated cationic amphiphilic lytic peptide.

Achieving effective intracellular delivery of therapeutic molecules such as antibodies (IgG) is a challenge in biomedical research and pharmaceutical development. Conjugation of IgG with a cell-penetrating peptide is a rational approach. Here, not only the efficacy of the conjugates in internalizing into cells, but also the physicochemical property of the conjugates allowing their solubilized states in solution without forming aggregates are critical. In this study, we have shown that the first requirement can be addressed using a cell-permeable attenuated cationic amphiphilic lytic (CP-ACAL) peptide, L17ER4. The second requirement can be addressed by ligation of IgG to L17ER4 using sortase A, where the use of a linker of appropriate chain length is also important. For evaluation, the intracellular delivery efficacy was studied using conjugate structures with different orientations and conjugation modes of L17ER4 in ligation to a model protein, green fluorescent protein fused to a nuclear localization signal (NLS-EGFP). The effect of tetraarginine positioning in the L17ER4 sequence was also investigated. Following these studies, an optimized peptide sequence containing L17ER4 was ligated to an anti-green fluorescent protein (GFP) IgG bearing a sortase A recognition sequence. Treatment of the cells with the conjugate of anti-GFP IgG and L17ER4 resulted in a high efficiency of cytosolic translocation of the conjugate and the binding to the target protein in the cell without significant aggregate formation. The feasibility of the d-form of L17ER4 as a CP-ACAL was also confirmed.

Current trends in development and manufacturing of higher-valent pneumococcal polysaccharide conjugate vaccine and its challenges.

Pneumococcal conjugate vaccines (PCVs) have been developed to protect against pneumococcal diseases caused by the more than 100 serotypes of the bacterium Streptococcus pneumoniae. PCVs primarily prevent pneumococcal infections such as sepsis, bacteraemia, meningitis, otitis media, pneumonia, septicaemia, and sinusitis among infants, adults, elderly, and immunocompromised individuals. The current available PCVs only cover a limited number of serotypes, and there is an immense need for developing higher-valent PCVs that can protect against non-vaccine serotypes to overcome challenges like serotype replacement and antibiotic resistance. The main challenges for developing higher valent PCVs are the complexity of the manufacturing process comprising polysaccharide fermentation, purification, modification or sizing of multiple polysaccharides and conjugation between polysaccharides and carrier proteins, the stability of the conjugates, and the immunogenicity of the vaccine. Different manufacturing processes have been explored to produce higher valent PCVs using different serotypes of S. pneumoniae and conjugation with different carrier proteins. The global coverage of higher valent PCVs are still low, mainly due to the high cost and limited supply of the vaccine. This review focuses on the existing and emerging manufacturing processes and challenges associated with higher-valent pneumococcal PCV development.

Ocular adverse events associated with antibody-drug conjugates for cancer: evidence and management strategies.

Antibody-drug conjugates (ADCs) are a fast-growing class of cancer drugs designed to selectively deliver cytotoxic payloads through antibody binding to cancer cells with high expression of the target antigen, thus reducing systemic exposure and minimizing off-target effects. However, ADCs are associated with various ocular adverse events (AEs) that may impact treatment administration and patient outcomes. In this review, we provide a summary of ocular AEs associated with approved and investigational ADCs, recommendations for the mitigation and management of ocular AEs, current guidelines and expert opinions, and recommendations for clinical practice. A literature search was performed, using PubMed and Google Scholar, for English-language articles published between January 1985 and January 2023 to identify studies reporting ocular AEs associated with ADC use. Search terms included generic and investigational names of all identified ADCs, and further searches were performed to identify strategies for managing ADC-associated ocular AEs. ADC-associated ocular AEs include symptoms such as blurred vision and foreign-body sensation and signs such as corneal fluorescein staining, corneal pseudomicrocysts, and conjunctivitis. Reported management strategies include ADC dose modification (eg, dose delay or reduction), cool compresses, artificial tears, topical vasoconstrictors, and topical steroids. Although ADC dose modification appears to be beneficial, the preventive and/or therapeutic benefits of the remaining interventions are unclear. Although the exact mechanisms are not fully understood, most ADC-associated ocular AEs are reversible with dose delay or dose reduction. Management of ocular AEs requires a multidisciplinary approach to minimize treatment discontinuation and optimize clinical outcomes.

An Investigation into the In Vitro Targeted Killing of CD44-Expressing Triple-Negative Breast Cancer Cells Using Recombinant Photoimmunotherapeutics Compared to Auristatin-F-Based Antibody-Drug Conjugates.

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer with limited treatment options. The persistence of highly tumorigenic CD44-expressing subpopulation referred to as cancer stem cells (CSCs), endowed with the self-renewal capacity, has been associated with therapeutic resistance, hence clinical relapses. To mitigate these undesired events, targeted immunotherapies using antibody-photoconjugate (APC) or antibody-drug conjugate (ADC), were developed to specifically release cytotoxic payloads within targeted cells overexpressing cognate antigen receptors. Therefore, an αCD44(scFv)-SNAP-tag antibody fusion protein was engineered through genetic fusion of a single-chain antibody fragment (scFv) to a SNAPf-tag fusion protein, capable of self-conjugating with benzylguanine-modified light-sensitive near-infrared (NIR) phthalocyanine dye IRDye700DX (BG-IR700) or the small molecule toxin auristatin-F (BG-AURIF). Binding of the αCD44(scFv)-SNAPf-IR700 photoimmunoconjugate to antigen-positive cells was demonstrated by confocal microscopy and flow cytometry. By switching to NIR irradiation, CD44-expressing TNBC was selectively killed through induced phototoxic activities. Likewise, the αCD44(scFv)-SNAPf-AURIF immunoconjugate was able to selectively accumulate within targeted cells and significantly reduced cell viability through antimitotic activities at nano- to micromolar drug concentrations. This study provides an in vitro proof-of-concept for a future strategy to selectively destroy light-accessible superficial CD44-expressing TNBC tumors and their metastatic lesions which are inaccessible to therapeutic light.

Antibody-Drug Conjugates: A Review of Cutaneous Adverse Effects.

Antibody-drug conjugates are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. Antibody-drug conjugates cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving antibody-drug conjugates, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the antibody-drug conjugates that have been approved for use by the U.S. Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with antibody-drug conjugates, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by antibody-drug conjugates.

Temperature- and pH-induced dual-crosslinked methylcellulose/chitosan-gallol conjugate composite hydrogels with improved mechanical, tissue adhesive, and hemostatic properties.

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities.

Injectable Hydrogel of Chitosan-Octyl Itaconate Conjugate Modulates Inflammatory Response.

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (ß-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma.

INTRODUCTION: Epithelial ovarian cancer (EOC) is associated with the highest gynecologic cancer mortality. The development of novel, effective combinations of targeted therapeutics remains an unmet medical need. We evaluated the preclinical activity of datopotamab deruxtecan (Dato-Dxd), a novel TROP2 targeting antibody drug conjugate (ADC) in ovarian cancer cell lines and xenografts with variable TROP2 expression. METHODS: In vitro cell viability with Dato-DXd was assessed using flow-cytometry based assays against a panel of EOC primary cell lines with variable TROP2 expression. Fluorescent anti-phospho-histone H2A.X antibody was used to detect dsDNA breaks by flow-cytometry. The in vivo antitumor activity of Dato-DXd was tested in TROP2 overexpressing xenografts. RESULTS: TROP2 overexpressing (3+) and moderate (2+) expressing EOC cell lines demonstrated higher sensitivity to Dato-DXd when compared to TROP2 negative tumors. Dato-DXd exposed TROP2+ EOC demonstrated increased dsDNA breaks and Annexin-V positivity (a marker of apoptosis) when compared to tumor cells exposed to the non-binding conjugate (p = 0.001 and p = 0.016, respectively). Dato-DXd induced significant antibody-dependent cellular cytotoxicity (ADCC) in the presence of peripheral-blood-lymphocytes. While negligible activity was detected against EOC cell lines with low TROP2 expression, Dato-DXd demonstrated significant bystander killing against tumor cells with low/negligible TROP2 when such cells were admixed with TROP2 3+ tumor cells in vitro. Dato-DXd showed tumor growth suppression against EOC cell line derived xenograft models that overexpress TROP2 at 3+ levels, prolonging survival when compared to controls, with minimal toxicity. CONCLUSION: Dato-DXd shows promising preclinical activity against TROP2 overexpressing ovarian cancers. Future clinical trials in ovarian cancer patients are warranted.

Polymer Conjugate as the New Promising Drug Delivery System for Combination Therapy against Cancer.

This review highlights the advantages of combination therapy using polymer conjugates as drug delivery systems for cancer treatment. In this review, the specific structures and materials of polymer conjugates, as well as the different types of combination chemotherapy strategies, are discussed. Specific targeting strategies, such as monoclonal antibody therapy and small molecule ligands, are also explored. Additionally, self-assembled polymer micelles and overcoming multidrug resistance are described as potential strategies for combination therapy. The assessment of combinational therapeutic efficacy and the challenges associated with polymer conjugates are also addressed. The future outlook aims to overcome these challenges and improve the effectiveness of drug delivery systems for combination therapy. The conclusion emphasizes the potential of polymer conjugates in combination therapy while acknowledging the need for further research and development in this field.

Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

Enhancing Performance of Organic Pollutant Degradation via Building Heterojunctions with ZnO Nanowires and Na Doped Conjugated 2,4,6-Triaminopyrimidin-g-C3N4.

Organic pollutants were one of the main sources of environmental pollutants. The degradation of organic pollutants through photocatalytic technology was one of the effective solutions. By preparing zinc oxide(ZnO) nanowires modified with sodium-doped conjugated 2,4,6-triaminopyrimidin-g-C3N4 (NaTCN) heterojunction (ZnO/NaTCN), the photocatalytic performance of NaTCN modified with different ratios of ZnO was systematically studied. The photocatalytic performance was studied through the degradation performance of methyl blue (MB) dye. The results showed that 22.5 wt% ZnO/NaTCN had the best degradation effect on MB dye. The degradation rate of MB reached 98.54% in 70 min. After three cycles, it shows good cycling stability (degradation rate is 96.99%) for dye degradation. It was found that there are two types of active species: ·OH and h+, of which h+ is the main active species produced by photocatalytic degradation of dyes. The excellent degradation performance was attributed to the fact that ZnO facilitated the extraction and transport of photogenerated carriers. The doping of sodium facilitated charge transfer. The NaTCN conjugated system promoted the extraction and transfer of photogenerated carriers. It provided guidance for designing efficient composite catalysts for use in other renewable energy fields.

Transition Metal-Catalyzed Transformations of Chalcones.

Chalcones are a class of naturally occurring flavonoid compounds associated to a variety of biological and pharmacological properties. Several reviews have been published describing the synthesis and biological properties of a vast array of analogues. However, overviews on the reactivity of chalcones has only been explored in a few accounts. To fill this gap, a systematic survey on the most recent developments in the transition metal-catalyzed transformation of chalcones was performed. The chemistry of copper, palladium, zinc, iron, manganese, nickel, ruthenium, cobalt, rhodium, iridium, silver, indium, gold, titanium, platinum, among others, as versatile catalysts will be highlighted, covering the literature from year 2000 to 2023, in more than 380 publications.

Utilising a 1,8-naphthalimide probe for the ratiometric fluorescent visualisation of caspase-3.

The development of selective and sensitive probes for monitoring caspase-3 activity-a critical enzyme involved in apoptosis-remains an area of significant interest in biomedical research. Herein, we report the synthesis and characterisation of a novel ratiometric fluorescent probe, Ac-DEVD-PABC-Naph, designed to detect caspase-3 activity. The probe utilises a 1,8-naphthalimide fluorophore covalently linked to a peptide sequence via a self-immolative p-aminobenzyl alcohol (PABA) linker. Upon enzymatic cleavage by caspase-3, the probe undergoes spontaneous degradation, releasing the free naphthalimide fluorophore, resulting in a ratiometric change in fluorescence emission. Spectroscopic studies revealed a time-dependent ratiometric fluorescent response, demonstrating the probe's ability to visualise caspase-3 activity with high sensitivity. Enzyme kinetics such as K m (Michaelis constant), k cat (turnover number), and LOD (Limit of Detection) were obtained, suggesting that the probe possesses comparable kinetic data to other probes in literature, but with the added benefits of ratiometric detection. Selectivity studies also demonstrated the probe's specificity for caspase-3 over other endogenous species and enzymes. Ac-DEVD-PABC-Naph may be a promising tool for the quantitative detection and fluorescent visualisation of caspase-3 activity in biological systems, with potential applications in apoptosis research and drug development.