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Endometrial cancer continues to be the only gynecologic malignancy with a rising incidence and mortality, with both regional and global implications. Combination carboplatin and paclitaxel has been the recognized chemotherapy backbone for the treatment of advanced‐stage or recurrent disease, with modest clinical outcomes. Over the last year, significant advances were achieved in improving oncologic outcomes by capitalizing on the molecular characterization of this heterogenous disease. These advances include incorporation of immunotherapy, identification of effective hormonal approaches, the evolution of antibody drug conjugates, and utilization of alternate targeted therapies. Plain Language Summary: The molecular characterization of endometrial cancer has been critical in informing novel treatment strategies.Over the past year, significant gains have been made via the incorporation of immunotherapy, hormonal combinations as well as antibody drug conjugates. Advanced stage and recurrence endometrial cancer remains difficult to treat. Recently, significant gains have been achieved in identifying effective therapeutic strategies by capitalizing on the molecular characterization of this heterogeneous disease. [ABSTRACT FROM AUTHOR]

Summary: Synthetic biology has the potential to revolutionize biotechnology, public health, and agriculture. Recent studies have shown the enormous potential of plants as chassis for synthetic biology applications. However, tools to precisely manipulate metabolic pathways for bioproduction in plants are still needed.We used bacterial allosteric transcription factors (aTFs) that control gene expression in a ligand‐specific manner and tested their ability to repress semi‐synthetic promoters in plants. We also tested the modulation of their repression activity in response to specific plant metabolites, especially phenylpropanoid‐related molecules. Using these aTFs, we also designed synthetic genetic circuits capable of computing Boolean logic operations.Three aTFs, CouR, FapR, and TtgR, achieved c. 95% repression of their respective target promoters. For TtgR, a sixfold de‐repression could be triggered by inducing its ligand accumulation, showing its use as biosensor. Moreover, we designed synthetic genetic circuits that use AND, NAND, IMPLY, and NIMPLY Boolean logic operations and integrate metabolite levels as input to the circuit.We showed that biosensors can be implemented in plants to detect phenylpropanoid‐related metabolites and activate a genetic circuit that follows a predefined logic, demonstrating their potential as tools for exerting control over plant metabolic pathways and facilitating the bioproduction of natural products. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Treponema is a Gram‐negative anaerobic bacterium, among which the pathogenic Treponema can cause various diseases, such as venereal syphilis (Treponema pallidum), yaws (Treponema carateum), and oral diseases (Treponema denticola and Treponema medium). Although different from conventional lipopolysaccharides, the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development. Hence, we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L‐ornithine (L‐Orn) and D‐aspartic acid (D‐Asp) derivatives. The efficiency of non‐reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors. Our [3+1] glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group, thereby improving the efficiency of synthesizing the target tetrasaccharide. The L‐Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. Therefore, the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional‐group modifications have provided valuable insights for synthesizing other complex bacterial glycans. [ABSTRACT FROM AUTHOR]

SUMMARY: L‐Arabinose (L‐Ara) is a plant‐specific sugar found in cell wall polysaccharides, proteoglycans, glycoproteins, and small glycoconjugates, which play physiologically important roles in cell proliferation and other essential cellular processes. L‐Ara is synthesized as UDP‐L‐arabinose (UDP‐L‐Ara) from UDP‐xylose (UDP‐Xyl) by UDP‐Xyl 4‐epimerases (UXEs), a type of de novo synthesis of L‐Ara unique to plants. In Arabidopsis, the Golgi‐localized UXE AtMUR4 is the main contributor to UDP‐L‐Ara synthesis. However, cytosolic bifunctional UDP‐glucose 4‐epimerases (UGEs) with UXE activity, AtUGE1, and AtUGE3 also catalyze this reaction. For the present study, we first examined the physiological importance of bifunctional UGEs in Arabidopsis. The uge1 and uge3 mutants enhanced the dwarf phenotype of mur4 and further reduced the L‐Ara content in cell walls, suggesting that bifunctional UGEs contribute to UDP‐L‐Ara synthesis. Through the introduction of point mutations exchanging corresponding amino acid residues between AtUGE1 with high UXE activity and AtUGE2 with low UXE activity, two mutations that increase relative UXE activity of AtUGE2 were identified. The crystal structures of AtUGE2 in complex forms with NAD+ and NAD+/UDP revealed that the UDP‐binding domain of AtUGE2 has a more closed conformation and smaller sugar‐binding site than bacterial and mammalian UGEs, suggesting that plant UGEs have the appropriate size and shape for binding UDP‐Xyl and UDP‐L‐Ara to exhibit UXE activity. The presented results suggest that the capacity for cytosolic synthesis of UDP‐L‐Ara was acquired by the small sugar‐binding site and several mutations of UGEs, enabling diversified utilization of L‐Ara in seed plants. [ABSTRACT FROM AUTHOR]

Aims: This study aims to develop a generalized pharmacokinetic (PK) model for monomethyl auristatin E (MMAE)‐based antibody–drug conjugates (ADCs) that can simultaneously capture the PK of multiple ADC analytes commonly measured in the clinic. Methods: A comprehensive literature review was conducted to collect PK data on MMAE‐based ADCs from clinical trials. From each study, PK profiles of total antibody, the ADC, conjugated MMAE, and unconjugated MMAE, were extracted. These data were pooled and dose‐normalized to evaluate the generalizability of PK across various ADCs and dose levels. Upon confirming PK generalizability, a generalized PK model for MMAE‐based ADCs was developed using the entire dataset. Furthermore, exposure metrics (Cmax and AUC) reported across the range of doses were combined to establish linear relationships between dose and exposure metrics for MMAE‐based ADCs. Results: A total of 109 PK profiles from 18 distinct MMAE‐based ADCs were gathered. The dose‐normalized PK profiles supported the generalizability of PK for MMAE‐based ADCs. A generalized PK model was developed, which enabled capturing the PK data for 4 ADC analytes across all collected MMAE‐based ADCs. A linear relationship between dose and PK exposure metrics was established, enabling the prediction of typical exposure values across different doses for MMAE‐based ADCs. Conclusions: This study comprehensively analysed clinical PK data from different valine–citrulline (vc)‐MMAE‐based ADCs. The generalized PK model developed here serves as an important tool for a priori prediction of the PK for multiple ADC analytes in clinical settings and lays the foundation for establishing generalized exposure–response and exposure–toxicity correlations for MMAE‐based ADCs. [ABSTRACT FROM AUTHOR]

The objective of the REALight project is the development of a thermal process to produce lightweight aggregates in pilot scale and the implantation of a method to recover gypsum. Beside construction and demolition waste, various industrial by‐products are studied as raw materials. The raw materials have so far been unused or used in applications with lower quality requirements. To prove the performance of the lightweight aggregates, their technical properties are tested and their use in different applications is studied, e.g., for lightweight mortars as well as lightweight concretes. [ABSTRACT FROM AUTHOR]

Summary: Ensuring the freshness of fish is essential to guaranteeing safer products for consumers. A classification model was developed using the PEN3 electronic nose to predict fish freshness with its storage day. Frigate tuna (Auxis thazard) was used for odour sampling along with the total volatile base nitrogen (TVB‐N), at 4 °C for 14 days every other day. Random forest and support vector machine (SVM) were performed to develop freshness classification models based on PEN3 data and 100% and 99.8% accuracies were obtained, respectively, in distinguishing the eight storage day classes. The PEN3 sensors including W2S, W1S, W1W, W3S, and W6S were identified as key sensors for fish freshness. TVB‐N analysis advances the freshness prediction of e‐nose and three freshness levels were identified as 'Fresh', applicable from the 0th to the 6th day; 'Moderately fresh', lasting from the 7th to the 9th day; and 'Unsuitable for consumption', applicable from the 10th day onwards. [ABSTRACT FROM AUTHOR]

Glycans, carbohydrates, and glycoconjugates are involved in many crucial biological processes, such as disease development, immune responses, and cell–cell recognition. Glycans and carbohydrates are known for the large number of isomeric features associated with their structures, making analysis challenging compared with other biomolecules. Mass spectrometry has become the primary method of structural characterization for carbohydrates, glycans, and glycoconjugates. Metal adduction is especially important for the mass spectrometric analysis of carbohydrates and glycans. Metal‐ion adduction to carbohydrates and glycoconjugates affects ion formation and the three‐dimensional, gas‐phase structures. Herein, we discuss how metal‐ion adduction impacts ionization, ion mobility, ion activation and dissociation, and hydrogen/deuterium exchange for carbohydrates and glycoconjugates. We also compare the use of different metals for these various techniques and highlight the value in using metals as charge carriers for these analyses. Finally, we provide recommendations for selecting a metal for analysis of carbohydrate adducts and describe areas for continued research. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Protein‐protein interactions (PPIs) play a crucial role in drug discovery and disease treatment. However, the development of effective drugs targeting PPIs remains challenging due to limited methodologies for probing their spatiotemporal anisotropy. Here, we propose a single‐molecule approach using a unique force circuit to investigate PPI dynamics and anisotropy under mechanical forces. Unlike conventional techniques, this approach enables the manipulation and real‐time monitoring of individual proteins at specific amino acids with defined geometry, offering insights into molecular mechanisms at the single‐molecule level. The DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques, facilitating orthogonal conjugation between proteins and nucleic acids. The SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force circuit. With the use of atomic force microscopy and magnetic tweezers, optimized assembly procedures were developed. The DNA force circuit provides an exceptional platform for studying the anisotropy of PPIs and holds promise for advancing drug discovery research targeted at PPIs. [ABSTRACT FROM AUTHOR]

The novel XOR, OR, and NAND optical logic gates have been investigated using GaAs‐based Hot Electron Light Emission and Lasing in Semiconductor Heterostructures (HELLISH) devices. The HELLISH devices are fabricated in the Top Hat‐HELLISH (TH‐HELLISH) geometry to achieve a nonlinear potential distribution at the p–n junction, which consists of a 13 nm thick GaAs quantum well placed on the n‐side of the junction. Logic gates whose input part is designed as an electric field output beam incorporate four independent contacts to the p‐ and n‐type layers. Electroluminescence measurements of the output beam are performed by applying a pulsed voltage of ≈150 V with a pulse width of 200 ns and a frequency of 20 kHz to the contacts of the TH‐HELLISH device. At room temperature, the primary emission wavelength of the optical logic gates is around 840 ± 1 nm. It is expected that optical logic gates obtained using this type of GaAs semiconductor structure have crucial potential to be components for high‐speed optical communication technology due to their simplicity, polarity‐independent operation, and emission wavelength. [ABSTRACT FROM AUTHOR]

The intrinsic quantum nature of molecules opens exciting opportunities for developing the field of quantum information science. In this context, porphyrins stand out as ideal building blocks for quantum technologies thanks to their unique optical and electrical properties as well as their capacity to accommodate metal atoms and ions. This review bridges the chemistry and physics of porphyrins, providing an overview of recent advances in porphyrin‐based molecular qubits. Starting from qubits, the review explores the potential of porphyrin units to combine, leading to the formation of quantum logic gates and hierarchical higher‐dimensional structures. Next, the exploitation of porphyrins' unique photophysical properties for realizing long‐lived high spin states is examined. These states are promising for the photogeneration of multi‐level systems and the optical initialization and control of molecular qubits. With a critical eye on the current state‐of‐the‐art, the review elucidates the future perspectives of porphyrins for advancing quantum technologies. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion To evaluate relationships between plasma concentrations of belantamab mafodotin, total monoclonal antibody, and its payload and changes in electrocardiogram (ECG) parameters in patients with relapsed or refractory multiple myeloma from the DREAMM‐1 and DREAMM‐2 studies.Hysteresis plots and linear regression analyses of pharmacokinetic (PK) analyte (belantamab mafodotin, total monoclonal antibody, and cytotoxic cysteine‐maleimidocaproyl monomethyl auristatin F payload) concentrations vs. time‐matched ECG parameters (absolute/change from baseline in QT interval corrected for RR interval [QTc/ΔQTc] and QT interval corrected for heart rate by Fridericia's formula [QTcF/ΔQTcF]) were performed. Concentrations of PK analyte required for a 10‐ms increase in QTc in DREAMM‐2 were calculated via simulation, as was the probability of ΔQTc/ΔQTcF exceeding 10 ms for the expected Cmax of PK analyte concentrations associated with the doses (2.5 and 3.4 mg/kg) administered in DREAMM‐2.Time‐matched PK and ECG data from 290 patients (DREAMM‐1, n = 73; DREAMM‐2, n = 217) were analysed. Hysteresis plots did not clearly indicate any concentration‐related prolongation in QTc or QTcF; regression analyses indicated a very small rate of increase in ΔQTc and ΔQTcF with increasing concentrations of PK analytes. Calculated concentrations of PK analyte required for a 10‐ms prolongation in QTc were higher than the maximum analyte concentrations observed following treatment with belantamab mafodotin in DREAMM‐2; the probability that each dose would prolong ΔQTc and ΔQTcF by >10 ms was 0 and <0.25%, respectively.This study of belantamab mafodotin and its payload did not provide evidence of QT prolongation in patients with relapsed or refractory multiple myeloma at clinically relevant doses. [ABSTRACT FROM AUTHOR]

The demand for stretchable strain sensors with customizable sensitivities has increased across a spectrum of applications, spanning from human motion detection to plant growth monitoring. Nevertheless, a major challenge remains in the digital fabrication of scalable and cost‐efficient strain sensors with tailored sensitivity to diverse demands. Currently, there is a lack of simple digital fabrication approaches capable of adjusting strain sensitivity in a controlled way with no changes to the material and without affecting the linearity. In this study, parallel microgates‐based strain sensors whose strain sensitivity can be adjusted systematically throughout an all‐laser‐based fabrication process without any material replacement are presented. The technique employs a two‐step direct laser writing method that combines the well‐established capabilities of laser ablation and laser marking, boasting a varying gauge factor of up to 433% (GF  =  168), while paving the way for the mass production of nanocomposite strain sensors. Parallel microgates‐based strain sensors exhibit a remarkable signal‐to‐noise ratio at ultralow strains (ɛ  =  0.001), rendering them ideal for monitoring the gradual growth of plants. As an application demonstration, the proposed sensors are deployed on tomato plants to capture their growth under varying planting conditions including hydroponic and soil mediums, as well as diverse irrigation regimens. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the potential utility of antibody‐drug conjugates targeting trophoblast cell surface antigen‐2 (TROP‐2) in patients with primary penile squamous cell carcinoma (PSCC), patients with recurrence (REC cohort), and patient‐matched distant metastases (MET cohort), and to assess the potential use of TROP‐2 as a predictive non‐invasive biomarker in PSCC.A cohort comprising a PRIM (n = 37), REC (n = 5) and MET subcohort (n = 7), with MET including lymph node and lung metastases, was analysed using quantitative real‐time PCR, ELISA and immunohistochemical staining with evaluation of H‐score.TROP‐2 mRNA and serum protein levels were significantly increased in primary and recurrent PSCC compared to cancer‐free controls (both P < 0.001). Immunohistochemical analysis revealed that most of the PRIM cohort (n = 34/37, median H‐score 260, interquartile range [IQR] 210–300), as well as all patients in the REC (median [IQR] H‐score 200 [165–290]) and MET cohorts (median [IQR] H‐score 280 [260–300]) exhibited moderate to strong membranous TROP‐2 expression. Additionally, The H‐score (membranous TROP‐2 expression) was positively correlated with TROP‐2 mRNA (ρ = 0.69, P < 0.0001, R2 = 0.70) and protein levels (ρ = 0.86, P < 0.0001, R2 = 0.59), indicating its potential as a non‐invasive biomarker in PSCC.In summary, our results support further studies on TROP‐2 as a diagnostic and therapeutic target in primary, recurrent and metastatic PSCC. [ABSTRACT FROM AUTHOR]

Purpose: Improved survival rates have been observed in castration‐resistant prostate cancer (CRPC) due to advancements in treatment options. However, individuals with brain metastases still have limited therapeutic options and an unfavorable prognosis. Therefore, there is an urgent need to explore new therapeutic avenues, such as antibody‐drug conjugates (ADCs), which have demonstrated significant clinical activity against active brain metastases in solid tumors. Our objective was to determine the expression levels of the ADC targets Trop‐2 and NECTIN‐4 in cerebral metastasized CRPC (mCRPC). Methods: Immunohistochemical staining of Trop‐2 and NECTIN‐4 with evaluation of H‐score was performed in CRPC brain metastases (n = 31). Additionally, we examined Trop‐2 protein expression in prostate cancer cell lines and studied their responsiveness to the anti‐Trop‐2 ADC Sacituzumab govitecan (SG) in vitro. Results: Our analysis revealed that most patients exhibited moderate to strong Trop‐2 expression [n = 27/31 with H‐score ≥100, median H‐score 220 (IQR 180–280)], while NECTIN‐4 was absent in all cerebral metastases. Mechanistically, we demonstrated that the efficacy of SG depends on Trop‐2 expression levels in vitro. Overexpression of Trop‐2 in Trop‐2‐negative PC‐3 cells led to sensitization to SG, whereas CRISPR‐Cas9‐mediated knockdown of Trop‐2 in Trop‐2‐expressing DU‐145 cells conferred resistance to SG. Conclusion: The substantial expression of Trop‐2 in cerebral metastases, along with our preclinical in vitro results, supports the efficacy of SG in treating cerebral mCRPC. Thus, our results extend the understanding of the potential of ADCs in prostate cancer treatment and provide an additional treatment strategy for the challenging subset of patients with cerebral metastases. [ABSTRACT FROM AUTHOR]

Lignin, a renewable aromatic polymer, has great potential as a synthetic building block for functional materials. The effects of quaternary ammonic methylation of alkali lignin (AL) on the morphologies and ofloxacin antibiotic (OA) removal application from water are investigated by using the dissipative particle dynamics (DPD) simulation method. Untreated AL can form spherical aggregates, but the phenylpropane units of untreated AL and loaded broad‐spectrum OA molecules are randomly distributed in aggregates. However, if quaternary ammonic groups are grafted onto all orthopositions of the phenolic hydroxyl groups (100‐QAMAL), then multilamellar spherical aggregates are obtained and OA molecules are entrapped in the aggregates. To prepare multilamellar spherical aggregates with an ordered and regular layered structure, <15 v% of 100‐QAMAL and low molecular weights of AL (≈4700–9400 Da) are suggested to be used. Lignin‐based multilamellar spherical aggregates can be adopted as potential functional carriers for removing pollutant OA from water. [ABSTRACT FROM AUTHOR]

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near‐infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agents for PA imaging. Silver (Ag) is particularly attractive because it has the strongest optical response and highest heat conductivity among plasmonic metals. The results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody‐like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, the AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high‐contrast PA imaging over multiple imaging sessions. Furthermore, the capability of the AgNAs are demonstrated for molecular PA cancer imaging in vivo by incorporating a tumor‐targeting peptide moiety. [ABSTRACT FROM AUTHOR]

Recently, electrochemical capacitor diodes (CAPodes) have been introduced as a new type of capacitive diode analogues. This device realizes unidirectional charging of ultracapacitors based on ion sieving mechanisms. Here, a new redox CAPode system is presented in which hydroxide ions react with nickel bismuth sulfide on nickel foam as a battery‐like electrode. This redox reaction leads to a high capacitance in a specific polarization window. However, for reversed bias this Faradaic electrode becomes inactive as it does not react with potassium cations, resulting in efficient blocking. By adapting counter electrode materials, mass loading, utilized substrates, and electrolyte concentrations a very high rectification ratio (RI = 37 and RII = 0.96 at 10 mV s−1) is achieved, significantly surpassing the performance of other reported redox‐type CAPodes. Moreover, this system shows an outstanding long‐term stability of a rectification retention of 90% for RII over 5000 repolarization cycles. Additionally, operando electrochemical measurements provide deep insights into the charge/discharge mechanism leading to a rationalization of the proposed concept. The integrated device, tested in logic gate circuits such as AND and OR gates, shows prospective results in ionologic applications. [ABSTRACT FROM AUTHOR]

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research. [ABSTRACT FROM AUTHOR]

Discussed are two picolinate appended bispidine ligands (3,7‐diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis‐pyridine derivative, which are all known to strongly bind CuII. The radiopharmacological characterization of the two isomeric bispidine complexes includes quantitative labeling with 64CuII at ambient conditions with high radiochemical purities and yields (molar activities >200 MBq/nmol). Challenge experiments in presence of EDTA, cyclam, human serum and SOD demonstrate high stability and inertness of the 64Cu‐bispidine complexes. Biodistribution studies performed in Wistar rats indicate a rapid renal elimination for both 64Cu‐labeled chelates. The bispidine ligand with the picolinate group in N7 position was selected for further biological experiments, and its backbone was therefore substituted with a benzyl‐NCS group at C9. Two tumor target modules (TMs), targeting prostate stem cell antigen (PSCA), overexpressed in prostate cancer, and the fibroblast activation protein (FAP) in fibrosarcoma, were selected for thiourea coupling with the NCS‐functionalized ligand and lysine residues of TMs. Small animal PET experiments on tumor‐bearing mice showed specific accumulation of the 64Cu‐labeled TMs in PSCA‐ and FAP‐overexpressing tumors (standardized uptake value (SUV) for PC3: 2.7±0.6 and HT1080: 7.2±1.25) with almost no uptake in wild type tumors. [ABSTRACT FROM AUTHOR]

Transition metal oxides (TMOs) are key in electrochemical energy storage, offering cost‐effectiveness and a broad potential window. However, their full potential is limited by poor understanding of their slow reaction kinetics and stability issues. This study diverges from conventional complex nano‐structuring, concentrating instead on spin‐related charge transfer and orbital interactions to enhance the reaction dynamics and stability of TMOs during energy storage processes. We successfully reconfigured the orbital degeneracy and spin‐dependent electronic occupancy by disrupting the symmetry of magnetic cobalt (Co) sites through straightforward strain stimuli. The key to this approach lies in the unfilled Co 3d shell, which serves as a spin‐dependent regulator for carrier transfer and orbital interactions within the reaction. We observed that the opening of these ′spin gates′ occurs during a transition from a symmetric low‐spin state to an asymmetric high‐spin state, resulting in enhanced reaction kinetics and maintained structural stability. Specifically, the spin‐rearranged Al−Co3O4 exhibited a specific capacitance of 1371 F g−1, which is 38 % higher than that of unaltered Co3O4. These results not only shed light on the spin effects in magnetic TMOs but also establish a new paradigm for designing electrochemical energy storage materials with improved efficiency. [ABSTRACT FROM AUTHOR]

Transition metal oxides (TMOs) are key in electrochemical energy storage, offering cost‐effectiveness and a broad potential window. However, their full potential is limited by poor understanding of their slow reaction kinetics and stability issues. This study diverges from conventional complex nano‐structuring, concentrating instead on spin‐related charge transfer and orbital interactions to enhance the reaction dynamics and stability of TMOs during energy storage processes. We successfully reconfigured the orbital degeneracy and spin‐dependent electronic occupancy by disrupting the symmetry of magnetic cobalt (Co) sites through straightforward strain stimuli. The key to this approach lies in the unfilled Co 3d shell, which serves as a spin‐dependent regulator for carrier transfer and orbital interactions within the reaction. We observed that the opening of these ′spin gates′ occurs during a transition from a symmetric low‐spin state to an asymmetric high‐spin state, resulting in enhanced reaction kinetics and maintained structural stability. Specifically, the spin‐rearranged Al−Co3O4 exhibited a specific capacitance of 1371 F g−1, which is 38 % higher than that of unaltered Co3O4. These results not only shed light on the spin effects in magnetic TMOs but also establish a new paradigm for designing electrochemical energy storage materials with improved efficiency. [ABSTRACT FROM AUTHOR]

Polatuzumab vedotin is a CD79b‐directed antibody–drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHP) as first‐line treatment of diffuse large B‐cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure–response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody‐conjugated (acMMAE)/unconjugated MMAE area under the concentration–time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression‐free and event‐free survival (both p = 0.01). An increase of <50% in acMMAE/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit–risk profile support the use of polatuzumab vedotin 1.8 mg/kg once every 3 weeks with R‐CHP for six cycles in patients with previously untreated DLBCL. [ABSTRACT FROM AUTHOR]

The strength and durability properties of the recycled aggregate concrete (RAC) have been affected by the cracks and the weak interfacial transition zone (ITZ) of the recycled coarse aggregates (RCA). However, the mechanical and physical features of RCA can be improved by microbially induced calcite precipitation (MICP). Therefore, immobilization techniques were used to protect and maintain the high efficiency of Bacillus bacteria for the formation and precipitation of calcium carbonates in self‐healing concrete over a period of time. The objective of the present study was to show the viability of the immobilized bacterial consortium‐enhanced RCA to form self‐healing cracks. Further, the self‐healing capability of enhanced RCA was investigated along with two other immobilization methods, that is, RCA and hydrated lime and brick powder (HBr)‐immobilized bacteria. The experimental results show that the increase in the bio‐deposition time improved the physical and mechanical properties of the RCA. Further, subsequently 56 days of the healing incubation period, the immobilized consortium‐enhanced RCA concrete specimens completely healed the cracks of width 0.58 mm. However, the equivalent cracks of width 0.56 mm were also recovered by the HBr immobilized bacterial cultures. Furthermore, the field emission scanning electron microscope (FESEM), energy dispersive spectroscopy (EDS) and X‐ray diffraction (XRD) analysis revealed that the existence of precipitation at the crack surface was calcium carbonate with a regular cubic‐shaped and lamellar layer morphology. The outcomes of the current study show that consortium‐enhanced RCA has promising potential to develop self‐healing concrete with self‐repaired and improved durability properties in the concrete construction field. [ABSTRACT FROM AUTHOR]

Oxovanadium (IV) and diphenyltin (IV) complexes were synthesized on the nanoscale based on the Schiff base (H2L) derived from salicylaldehyde and d‐glucosamine. The complexes were formed with a molar ratio of 1:1 and 1:2 (metal: dligand) relative to oxovanadium (IV) and diphenyltin (IV), respectively. Fourier‐transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance, mass fragmentations, electronic transitions, thermogravimetric analysis, and density functional theory were employed to validate the structure of synthesized compounds. The results demonstrated that the ligand (H2L) was successfully attached to oxovanadium (IV) and diphenyltin (IV) as di‐anionic and mono‐anionic ligands, respectively. The size of the complexes was investigated using the transmission scanning microscope. The work presents a prospective concept for the drug design of the targeted anticancer through the glucose moiety. All compounds revealed remarkable anticancer activities against the colorectal (HCT‐116) cell line, recording IC50 values 4.94, 21.73, and 62.5 μg/ml for VO (II)(L), free H2L, and Sn (ph)2(HL)2, respectively. The IC50 value of VO (II)(L) complex was increased after the quercetin inhibitor. Therefore, the sugar‐conjugated compound can be recognized by the glucose recognition binding site of GLUT and their cell‐killing effect depends highly on the GLUT inhibitor, quercetin. The potential GLUT transportability of the compounds was investigated through a molecular docking study. The anti‐migration activity was investigated for VO (II)(L) complex. The free ligand observed the best antimicrobial results. The antibacterial stimulation was investigated and represented different interaction types with the selected ribosyl transferase enzyme. [ABSTRACT FROM AUTHOR]

Conjugates of chlorins with β‐cyclodextrin connected either directly or via a flexible linker were prepared. In aqueous medium these amphiphilic conjugates were photostable, produced singlet oxygen at a rate similar to clinically used temoporfin and formed irregular nanoparticles via aggregation. Successful loading with the chemotherapeutic drug tamoxifen was evidenced in solution by the UV‐Vis spectral changes and dynamic light scattering profiles. Incubation of MCF‐7 cells with the conjugates revealed intense spotted intracellular fluorescence suggestive of accumulation in endosome/lysosome compartments, and no dark toxicity. Incubation with the tamoxifen‐loaded conjugates revealed also practically no dark toxicity. Irradiation of cells incubated with empty conjugates at 640 nm and 4.18 J/cm2 light fluence caused >50 % cell viability reduction. Irradiation following incubation with tamoxifen‐loaded conjugates resulted in even higher toxicity (74 %) indicating that the produced reactive oxygen species had triggered tamoxifen release in a photochemical internalization (PCI) mechanism. The chlorin‐β‐cyclodextrin conjugates displayed less‐lasting effects with time, compared to the corresponding porphyrin‐β‐cyclodextrin conjugates, possibly due to lower tamoxifen loading of their aggregates and/or their less effective lodging in the cell compartments' membranes. The results suggest that further to favorable photophysical properties, other parameters are important for the in vitro effectiveness of the photodynamic systems. [ABSTRACT FROM AUTHOR]

Summary: In today's consumer landscape, the health benefits of preserved foods, particularly pickled and salted mustard greens, are gaining recognition on a global scale. To compare health‐promoting compounds between fresh and preserved mustard greens, a comprehensive assessment using proximate composition analysis and untargeted metabolomics was conducted. The sub‐metabolome data revealed distinct profiles for each type of mustard greens, clearly seen in their separation through principal component analysis. The metabolite profiling identified 37 metabolites with significant differences (P‐value < 0.05, −log10 P‐value > 4). Fresh mustard greens were found to be rich in 16 identified metabolites, including sulfonic acids, purines, oxepanes, monosaccharides, fatty acids, amino acids and tripeptides, offering antioxidants, gut enhancers and immune boosters. In contrast, pickled mustard greens exhibited an abundance of 20 identified metabolites in the classes of flavonoids, amino acids and dipeptides, providing antioxidant properties. Salted mustard greens, on the other hand, primarily showcased a high level of uridine diphosphate glucose (a pyrimidine class metabolite), supporting glycoconjugate synthesis among all samples. This study highlights the prominent presence of various classes of metabolites associated with health‐benefit compounds in fresh and preserved mustard greens. These insights contribute to the evaluation of health benefits in the food industry when choosing between pickled and salted preservation methods. [ABSTRACT FROM AUTHOR]

Objective: In December 2021, enfortumab vedotin (EV), an antibody‐drug conjugate directed against nectin‐4, was approved in Japan as a new treatment after platinum‐containing chemotherapy and PD‐1/PD‐L1 inhibitors. This study evaluated, using real‐world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). Materials and methods: Fifty‐five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non‐EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. Results: The median (range) follow‐up period after pembrolizumab discontinuation was 6.3 (0.7–31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non‐EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non‐EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non‐EV group; hazard ratio 0.26; 95% confidence interval 0.16–0.41; p < 0.001) was an independent prognostic factor for OS. Conclusion: EV prolonged OS in mUC following pembrolizumab therapy in real‐world data. [ABSTRACT FROM AUTHOR]

Non‐enzymatic glycation and oxidation of self‐proteins, causing formation and accumulation of advanced glycation end products (AGEs), have been reported in an array of pathologies, including systemic lupus erythematosus (SLE). Such modifications may generate neo‐epitopes, break immunological tolerance, and induce antibody response. In this study, we have first analysed the structural modifications of whole histone in the presence of deoxyribose followed by oxidation with hydroxyl radicals. Changes in the secondary and tertiary structure of the whole histone were determined by spectroscopic techniques and biochemical assays. Fluorescence spectroscopy and UPLC–MS showed the generation of AGEs such as carboxymethyl lysine and pentosidine, while DLS and TEM indicated the presence of amorphous AGE‐aggregates. Moreover, rabbits immunized with these histone‐AGEs exhibited enhanced immunogenicity and ELISA and western immunoblot of IgG antibodies from SLE patients' sera showed a significantly higher specificity towards modified histone‐AGEs than the native histone. [ABSTRACT FROM AUTHOR]

First‐line treatment of multiple myeloma, a prevalent blood cancer lacking a cure, using anti‐CD38 daratumumab antibody and lenalidomide is often inadequate due to relapse and severe side effects. To enhance drug safety and efficacy, an antibody‐drug conjugate, TE‐1146, comprising six lenalidomide drug molecules site‐specifically conjugated to a reconfigured daratumumab to deliver cytotoxic lenalidomide to tumor cells is developed. TE‐1146 is prepared using the HighDAR platform, which employs i) a maleimide‐containing "multi‐arm linker" to conjugate multiple drug molecules creating a drug bundle, and ii) a designed peptide with a Zn2+‐binding cysteine at the C‐termini of a reconfigured daratumumab for site‐specific drug bundle conjugation. It is shown that TE‐1146 remains intact and effectively enters CD38‐expressing tumor cells, releasing lenalidomide, leading to enhanced cell‐killing effects compared to lenalidomide/daratumumab alone or their combination. This reveals the remarkable potency of lenalidomide once internalized by myeloma cells. TE‐1146 precisely delivers lenalidomide to target CD38‐overexpressing tumor cells. In contrast, lenalidomide without daratumumab cannot easily enter cells, whereas daratumumab without lenalidomide relies on Fc‐dependent effector functions to kill tumor cells. [ABSTRACT FROM AUTHOR]

Tubulysins are among the most recent antimitotic compounds to enter into antibody/peptide‐drug conjugate (ADC/PDC) development. Thus far, the design of the most promising tubulysin payloads relied on simplifying their structures, e. g., by using small tertiary amide N‐substituents (Me, Et, Pr) on the tubuvaline residue. Cumbersome solution‐phase approaches are typically used for both syntheses and functionalization with cleavable linkers. p‐Aminobenzyl quaternary ammonium (PABQ) linkers were a remarkable advancement for targeted delivery, but the procedures to incorporate them into tubulysins are only of moderate efficiency. Here we describe a novel all‐on‐resin strategy permitting a loss‐free resin linkage and an improved access to super potent tubulysin analogs showing close resemblance to the natural compounds. For the first time, a protocol enables the integration of on‐resin tubulysin derivatization with, e. g., a maleimido‐Val‐Cit‐PABQ linker, which is a notable progress for the payload‐PABQ‐linker technology. The strategy also allows tubulysin diversification of the internal amide N‐substituent, thus enabling to screen a tubulysin library for the discovery of new potent analogs. This work provides ADC/PDC developers with new tools for both rapid access to new derivatives and easier linker‐attachment and functionalization. [ABSTRACT FROM AUTHOR]

Recent studies have shown that active colloidal motors using enzymatic reactions for propulsion hold special promise for applications in fields ranging from biology to material science. It will be desirable to have active colloids with capability of computation so that they can act autonomously to sense their surroundings and alter their own dynamics. It is shown how small chemical networks that make use of enzymatic chemical reactions on the colloid surface can be used to construct motor‐based chemical logic gates. The basic features of coupled enzymatic reactions that are responsible for propulsion and underlie the construction and function of chemical gates are described using continuum theory and molecular simulation. Examples are given that show how colloids with specific chemical logic gates, can perform simple sensing tasks. Due to the diverse functions of different enzyme gates, operating alone or in circuits, the work presented here supports the suggestion that synthetic motors using such gates could be designed to operate in an autonomous way in order to complete complicated tasks. [ABSTRACT FROM AUTHOR]

Multicomponent reactions are operationally simple and display a significant role in diverse chemical modification by reducing reaction times as well as additional steps involved. In this review, we highlighted the impact of multi‐component reactions in assistance with modular Click chemistry to develop a library of triazole‐appended scaffolds including 1,2,3‐triazole‐fused heterocycles, glycoconjugates, macrocycles as well as in the combinatorial synthesis of differently functionalized triazoles along with mechanistic insights with a diverse range of applications in the field of medicinal chemistry. [ABSTRACT FROM AUTHOR]

2‐Nitroglycals are important synthons for biological active 2‐aminoglycosides, glycoconjugates and natural products synthesis. Herein, we summarized the recent advances of 2‐nitroglycals including its synthetic methods and its applications. Using 2‐nitroglycals, 2‐aminoglycosides, nitro‐polyol derivatives, sugar‐furan derivatives, sugar‐pyrrole molecules, 2,3‐diaminoglycosides and 2‐amino‐1,3‐dithioglycosides were obtained via Michael–type addition, retro‐Henry‐type reaction, C1/C3‐Ferrier rearrangement and [3+2] N‐heterocyclic addition. Most of these conversions are achieved via mild organo‐catalysis glycosylation methods. [ABSTRACT FROM AUTHOR]

Peptide−oligonucleotide conjugates (POCs) are covalent architectures composed of a DNA or RNA molecules linked to a peptide. These constructs have found widespread applications ranging from hybrid nanomaterials to gene‐targeted therapies. Considering the important role of POCs, a new catalytic approach for their preparation is reported here, that could be applied either on solid support in anhydrous media, or post‐synthetically in aqueous buffer. Single amino acids, peptides and cell penetrating peptides (CPPs) were conjugated to various oligo(ribo)nucleotides with high conversions and good isolated yields. The applicability of the method was demonstrated on more than 35 examples including an analogue of a commercial therapeutic oligonucleotide. Other conjugation partners, such as deoxycholic acid and biotin were also successfully conjugated to oligonucleotides. To highlight the potential of this catalytic approach, these conditions have been applied to iterative processes, which is of high interest for the development of DNA‐Encoded Libraries. [ABSTRACT FROM AUTHOR]

The aggregation of amyloid peptides and proteins into toxic oligomers is a hallmark of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Machado‐Joseph's disease, and transmissible spongiform encephalopathies. Inhibition of amyloid oligomers formation and interactions with biological counterparts, as well as the triggering of non‐toxic amorphous aggregates, are strategies towards preventive interventions against these pathologies. NMR spectroscopy addresses the need for structural characterization of amyloid proteins and their aggregates, their binding to inhibitors, and rapid screening of compound libraries for ligand identification. Here we briefly discuss the solution experiments constituting the NMR spectroscopist‘s toolkit and provide examples of their application. [ABSTRACT FROM AUTHOR]

The development of innovative antifungal medications to address the issues of indiscriminate antifungal use contributes to certain antifungal drug resistance. To tackle this issue, we have designed and synthesized novel amino acids naphthalene scaffolds (6 a–6 i) (Scheme 1) by acid amine coupling between compound 5 and various amino acids. Moreover, we evaluated the antifungal, anti‐bacterial and antimalarial activities of synthesized derivatives. Among them, compounds Met (6 a), Phe (6 c), Lys (6 d), Ser (6 f), and Tyr (6 i) expressed excellent antifungal activity at a minimum inhibitory concentration (MIC) value of 250 μg/mL against Candida albicans compared to standard drug griseofulvin (500 μg/mL). The antibacterial assay results showed that compound Met (6 a) exhibited effective antibacterial activity at MIC value at 50 and 62.5 μg/mL against Streptococcus pyogenes and Pseudomonas aeruginosa respectively, and compound Trp (6 g) showed very good antibacterial activity at MIC 62.5 μg/mL against Staphylococcus aureus. The antimalarial activity of synthesized compoundsVal (6 b) and Lys (6 d) showed moderately active with mean IC50 of 0.69 and 0.47 μg/mL, respectively compared with standard drug quinine (IC50=0.26 μg/mL). Also, a molecular docking study was performed to demonstrate the binding energy of synthesized scaffoldswith effective interaction with various proteins. The compound Met (6 a) showed that the highest binding affinity (binding energy: −7.1 kcal/mol) which interacted more effectively with VAL 120 (2.90 Å). [ABSTRACT FROM AUTHOR]

The aggregation‐induced emission (AIE) properties of a systematic series of naphthalene diimides (NDIs) varying the chain length at the imide positions have been studied. A solvophobic collapse of NDI units through the flash injection of THF NDI solutions in sonicating water triggers the formation of stable suspensions with enhanced fluorescence emissions. Shorter chains favor the π‐π stacking of NDI units through H‐aggregation producing a strong AIE effect showing remarkably high quantum yields that have not been observed for non core‐substitued NDIs previously. On the other hand, NDIs functionalized with longer chains lead to more disordered domains where π‐π stacking between NDI units is mainly given by J‐aggregation unfavoring the AIE effect. [ABSTRACT FROM AUTHOR]

Although natural products are essential sources of small‐molecule antitumor drugs, some can exert substantial toxicities, limiting their clinical utility. Anthraquinone‐fused enediyne natural products are remarkably potent antitumor drug candidates, and uncialamycin and tiancimycin (TNM) A are under development as antibody‐drug conjugates. Herein, a novel drug delivery system is introduced for TNM A using anti‐human epidermal growth factor receptor 2 (HER2) immunoliposomes (ILs). Trastuzumab‐coated TNM A‐loaded ILs (HER2‐TNM A‐ILs) is engineered with an average particle size of 182.8 ± 2.1 nm and a zeta potential of 1.75 ± 0.12 mV. Compared with liposomes lacking trastuzumab, HER2‐TNM A‐ILs exhibited selective toxicity against HER2‐positive KPL‐4 and SKBR3 cells. Coumarin‐6, a fluorescent TNM A surrogate, is encapsulated within anti‐HER2 ILs; the resultant ILs have enhanced cellular uptake in KPL‐4 and SKBR3 cells when compared with control liposomes. Furthermore, ILs loaded with more Cy5.5 accumulated in KPL‐4 mouse tumors. A single HER2‐TNM A‐IL dose (0.02 mg kg−1) suppressed the growth of HER2‐positive KPL‐4 mouse tumors without apparent toxicity. This study not only provides a straightforward method for the effective delivery of TNM A against HER2‐positive breast tumors but also underscores the potential of IL‐based drug delivery systems when employing highly potent cytotoxins as payloads. [ABSTRACT FROM AUTHOR]

As a crucial component of superconducting quantum computing, the three‐energy‐level quantum system, known as qutrit, along with qutrit gates, has garnered significant attention over the past decades, which highlights the significance of accomplishing state transfers between levels in multiqutrit systems as a critical task. Herein, the |fg⟩−|ge⟩$\left|\right. f g \rangle - \left|\right. g e \rangle$ coupling is constructed via the all‐microwave approach. Both the coupling strength and Alternating Current stark shift are calibrated, based on which a fast (70 ns) state transfer from |gf⟩$\left|\right. g f \rangle$ to |fg⟩$\left|\right. f g \rangle$ is investigated and achieved through the stimulated Raman shortcut‐to‐adiabatic passage. [ABSTRACT FROM AUTHOR]

Longitudinal coupling, which generates entanglement without energy exchange, has extensive applications in quantum computing and quantum simulation. However, achieving available direct and flexible longitudinal couplings between highly coherent superconducting qubits is challenging. In this study, a method is developed to achieve direct and flexible longitudinal couplings between superconducting qubits, including the direct longitudinal coupling between capacitively shunted flux qubits (C‐shunt flux qubits) and that between transmon qubits. Herein, first, a variant of the prototype C‐shunt flux qubit, the concentric C‐shunt flux qubit, is introduced. It is demonstrated that the large mutual inductance between concentric C‐shunt flux qubits produces a longitudinal coupling strength up to 21 MHz. It is also demonstrated that the method can be used to realize a strong longitudinal coupling between two transmon qubits. In the findings, it is demonstrated that it is possible to achieve a flexible and efficient direct longitudinal coupling between superconducting qubits, and open up new possibilities for the development of quantum gate operation methods as well as quantum simulation methods. [ABSTRACT FROM AUTHOR]

Influence of recycled aggregate on the bond behaviour of reinforcing steel in concrete The use of recycled aggregates in common structural concretes is considered a promising approach to conserve natural resources. The present study focuses on investigating the bond behaviour of reinforcing steel in concrete with high portions of recycled aggregate from crushed concrete. To clarify a possible influence of the aggregate properties, 5 different aggregates were tested in 12 concretes. The results of the pull‐out tests were evaluated with the help of an analytical bond equation to be able to draw conclusions about the resulting design bond stress. A tendency towards a decrease in the maximum absorbable bond stress with high portions of recycled aggregate was observed. The resulting design values of the bond strength are lower than for the reference concrete, but above the specifications of Eurocode 2. The decrease in the design bond stress appears to correlate with the volume fractions of recycled aggregate and the concrete bulk density. Overall, the study shows that the bond behaviour of concrete with recycled aggregate is similar to that of normal concrete in terms of bond, shear and friction, although the actual effects also depend on the specific properties of the aggregate used. [ABSTRACT FROM AUTHOR]

Methods for quantifying the CO2 storage potential of recycled aggregates The necessity of utilizing CO2 sinks is becoming increasingly relevant for the construction industry, as the manufacturing of certain industrial goods will process‐related continue to produce emissions. An innovative approach to this is the utilization of waste concrete respectively recycled aggregates produced from it for CO2 sequestration, which expands the recycling of construction waste in the context of resource conservation (Urban Mining) to include climate compatibility. Initial implementations in practice have already occurred, and an increasing future application is emerging. One challenge lies in the uncertainty regarding the CO2 uptake potential of the recycled aggregates. Accurate assessment is essentially possible only after carbonation has taken place by determining the masses and monitoring the experimental conditions. The primary influencing parameters are the grain size and the time available for carbonation, as well as the concrete properties and exposure conditions of the available waste concrete. This article presents a practical method by which the respective carbonation potential can be determined prior to demolition of a structure providing a simple, manageable means to evaluate the effectiveness of the additional required processing step. [ABSTRACT FROM AUTHOR]

Acylated N‐acetyl hexosamine hemiacetals are known for their cytotoxicity. We have previously reported that cytotoxicity can be increased by replacing one or more acyloxy groups with fluorine. Herein, we present the synthesis of 4,6‐difluorinated d‐gluco‐ and 4‐fluorinated d‐galacto‐configured hexosamine‐derived glycoconjugates with organoruthenium or ferrocene complexes and their in vitro cytotoxicity against three cancer cell lines (A2780, SK‐OV‐3, and MDA‐MB‐231) and one noncancerous cell line (HEK‐293). The attachment of the organometallic moiety at the 2‐position significantly enhanced the cytotoxicity, especially against triple‐negative MDA‐MB‐231 and the cisplatin resistant SK‐OV‐3 cancer cells. We observed a clear significance of an unprotected and acetyl protected anomeric hydroxyl for the cytotoxicity. Glycoconjugates with a non‐hydrolysable organic or organometallic group at the anomeric position were generally nontoxic. A more detailed analysis revealed that, in particular, complexes with the ruthenium tetrazene complex induced apoptosis in both SK‐OV‐3 and MDA‐MB‐231 cells, as demonstrated by western blot analysis and Annexin V‐FITC/PI staining. The structures of the two most cytotoxic organoruthenium and ferrocene glycoconjugates were confirmed by X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Summary: Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple‐class refractory disease. We report the use of belantamab mafodotin, a BCMA‐directed drug–antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty‐one patients were reviewed, with a median of three prior lines of therapy. The median follow‐up was 12 months (95% CI 4–19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty‐eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This clinical case report focuses on a case of surgery performed on a patient with the aim of cutting the dental apices in the patient's upper jaw. Mineral trioxide aggregate (MTA) was used as a filling material, and monitoring the condition showed that the operation was successful. [ABSTRACT FROM AUTHOR]

In this work, microporous MgO–Al2O3 refractory aggregates were prepared with Mg(OH)2 and Al(OH)3 via the in situ decomposition synthesis method. The effect of Al(OH)3 addition on the microstructure and properties of microporous MgO–Al2O3 refractory aggregates was investigated with scanning electron microscope and mercury intrusion porosimetry. The results indicated that the improved green density of the samples and the reaction sintering accelerated the mass transport rate with adding Al(OH)3 from 0 to 4.0 wt%. Besides, a small amount of Al3+ diffused into porous MgO particles, accelerating the merging and growth of nanopores in the porous MgO particles. The intra‐particle pore size and the densification degree of microparticles were increased, and thus the strength of the samples was improved. Due to the formation of Kirkendall voids by interdiffusion of Mg2+ and Al3+, the inter‐particle pore size increased. Adding Al(OH)3 from 4.0 to 17.6 wt%, the Kirkendall voids weakened the mass transport rate and improved the inter‐particle pore size. The merging and growth of nanopores in the MgO particles were limited, resulting in the reduced intra‐particle pore size and increased intra‐particle pore number. The densification degree of microparticles was reduced, and thus the strength of the samples decreased. At the Al(OH)3 addition of 4.0 wt%, microporous MgO–Al2O3 refractory aggregates had the best comprehensive properties, a bulk density of 2.48 g/cm3, an apparent porosity of 29.4%, a median pore size of 1.6 μm with 42.2 vol% nanopores and the thermal conductivity of 4.0 W/(m K). [ABSTRACT FROM AUTHOR]

Surface enhanced resonance Raman (SERS) is a powerful optical technique, which can help enhance the sensitivity of Raman spectroscopy aided by noble metal nanoparticles (NPs). However, current SERS‐NPs are often suboptimal, which can aggregate under physiological conditions with much reduced SERS enhancement. Herein, a robust one‐pot method has been developed to synthesize SERS‐NPs with more uniform core diameters of 50 nm, which is applicable to both non‐resonant and resonant Raman dyes. The resulting SERS‐NPs are colloidally stable and bright, enabling NP detection with low‐femtomolar sensitivity. An algorithm has been established, which can accurately unmix multiple types of SERS‐NPs enabling potential multiplex detection. Furthermore, a new liposome‐based approach has been developed to install a targeting carbohydrate ligand, i.e., hyaluronan, onto the SERS‐NPs bestowing significantly enhanced binding affinity to its biological receptor CD44 overexpressed on tumor cell surface. The liposomal hyaluronan (HA)‐SERS‐NPs enabled visualization of spontaneously developed breast cancer in mice in real time guiding complete surgical removal of the tumor, highlighting the translational potential of these new glyco‐SERS‐NPs. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody‐drug conjugate (ADC) therapy. Methods: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT‐PCR, Western Blot analysis, and ELISA. Results: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer‐derived extracellular vesicles. Moreover, LGALS3BP high‐expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC‐payload DM4, with an IC50 around 0.3 nM. Conclusions: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC‐based therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Theabrownins (TBs) are one of most important quality components in dark tea, but have not been produced industrially. In this study, the aqueous extract was obtained from Pu‐erh ripe tea, one kind of dark tea. Caffeine, theaflavin, catechin and saponin were removed by trichloromethane, ethyl acetate and n‐butanol in turn to obtain a TB isolate. The TB isolate was subjected to column chromatography using a macroporous resin HPD‐750 and eluted with a gradient of 0–700 g kg−1 ethanol aqueous solution. Four fractions were obtained, and named as TBs‐FC1, TBs‐FC2, TBs‐FC3 and TBs‐FC4. RESULTS: These four fractions contained polysaccharides and no small molecules such as catechins, caffeine and theaflavins as well as average molecular weights of 123.000 kDa, 23.380 kDa, 89.870 kDa and 106.600 kDa. It was revealed that they were complexes of TBs and tea polysaccharide conjugates (TPCs). Ultraviolet‐visible (UV‐visible) and infrared (IR) spectra showed the properties of TBs and TPCs. Their zeta potentials ranged from −13.40 mV to −38.80 mV in aqueous solutions at pH 3.0–9.0. CONCLUSION: This study reveals that TBs do not exist in free state but in combined state in dark tea, which provide the theoretical basis for the industrialization of TBs. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]