Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses.

Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6+ type 3 innate lymphoid cells (ILC3s) can trigger an increase in the number of T cells infiltrating a tumor. Shortly after administration of cisplatin chemotherapy, production of the chemokine CCL20 and proinflammatory cytokine IL-1ß at the tumor site led to the recruitment and activation of ILC3s. Within the tumor, ILC3 production of the chemokine CXCL10 was responsible for the recruitment of CD4+ and CD8+ T lymphocytes to the tumor. ILC3-dependent infiltration of T cells was essential for antitumor immune responses and increased the efficacy of checkpoint inhibition. Thus, we reveal an essential role of CCL20 and IL-1ß, which promote ILC3-dependent antitumor immunity and enhance tumor sensitivity to immunotherapy.

From the design of innovative Ti-Pt heterometallic complexes to the development of highly anti-proliferative water-soluble cationic titanocenes.

Two innovative early/late Ti-Pt-heterobimetallic complexes were synthesized, characterized, and screened in cell-based assays using several human (SW480 and MDA-MB-231) and murine cancer cell lines (CT26 and EMT6) as well as a non-cancerous cell line (HMEC). The combination of the two metals - titanium(IV) and platinum (IV) - in a single molecule led to a synergistic biological activity (higher anti-proliferative properties than a mixture of each of the corresponding monometallic complexes). This study also investigated the benefits of associating a metal-free terpyridine moiety (with intrinsic biological activity) with a water-soluble titanocene fragment. The present work reveals that these combinations results in water-soluble titanocene compounds displaying an anti-proliferative activity down to the submicromolar level.  One of these complexes induced an antitumor effect in vivo in CT26 tumor bearing BALB/C mice. The terpyridine moiety was also used to track the complex in vitro by multiphoton microscopy imaging.

First Comparison Study of the In Vitro and In Vivo Properties of a Randomly and Site-Specifically Conjugated SPECT/NIRF Monomolecular Multimodal Imaging Probe (MOMIP) Based on an aza-BODIPY Fluorophore.

Among all approaches in molecular imaging, the combination of near-infrared fluorescence imaging (NIRF) with radioisotopic imaging (PET or SPECT) allows one to benefit from the advantages of each of the imaging techniques, which are very complementary and of comparable sensitivity. To this end, the construction of monomolecular multimodal probes (MOMIP) has made it possible to combine the two imaging modalities within the same molecule, thus limiting the number of bioconjugation sites and yielding more homogeneous conjugates compared with those prepared through sequential conjugation. However, in order to optimize the bioconjugation strategy and, at the same time, the pharmacokinetic and biodistribution properties of the resulting imaging agent, a site-specific approach may be preferred. To further investigate this hypothesis, random and glycan-based site-specific bioconjugation approaches were compared thanks to a SPECT/NIRF bimodal probe based on an aza-BODIPY fluorophore. The overall experiments conducted in vitro and in vivo on HER2-expressing tumors demonstrated a clear superiority of the site-specific approach to improve affinity, specificity, and biodistribution of the bioconjugates.

Investment case for small and sick newborn care in Tanzania: systematic analyses.

BACKGROUND: Small and sick newborn care (SSNC) is critical for national neonatal mortality reduction targets by 2030. Investment cases could inform implementation planning and enable coordinated resource mobilisation. We outline development of an investment case for Tanzania to estimate additional financing for scaling up SSNC to 80% of districts as part of health sector strategies to meet the country's targets. METHODS: We followed five steps: (1) reviewed national targets, policies and guidelines; (2) modelled potential health benefits by increased coverage of SSNC using the Lives Saved Tool; (3) estimated setup and running costs using the Neonatal Device Planning and Costing Tool, applying two scenarios: (A) all new neonatal units and devices with optimal staffing, and (B) half new and half modifying, upgrading, or adding resources to existing neonatal units; (4) calculated budget impact and return on investment (ROI) and (5) identified potential financing opportunities. RESULTS: Neonatal mortality rate was forecast to fall from 20 to 13 per 1000 live births with scale-up of SSNC, superseding the government 2025 target of 15, and close to the 2030 Sustainable Development Goal 3.2 target of <12. At 85% endline coverage, estimated cumulative lives saved were 36,600 by 2025 and 80,000 by 2030. Total incremental costs were estimated at US$166 million for scenario A (US$112 million set up and US$54 million for running costs) and US$90 million for scenario B (US$65 million setup and US$25 million for running costs). Setup costs were driven by infrastructure (83%) and running costs by human resources (60%). Cost per capita was US$0.93 and the ROI is estimated to be between US$8-12 for every dollar invested. CONCLUSIONS: ROI for SSNC is higher compared to other health investments, noting many deaths averted followed by full lifespan. This is conservative since disability averted is not included. Budget impact analysis estimated a required 2.3% increase in total government health expenditure per capita from US$40.62 in 2020, which is considered affordable, and the government has already allocated additional funding. Our proposed five-step SSNC investment case has potential for other countries wanting to accelerate progress.

Protecting small and sick newborn care in the COVID-19 pandemic: multi-stakeholder qualitative data from four African countries with NEST360.

BACKGROUND: Health system shocks are increasing. The COVID-19 pandemic resulted in global disruptions to health systems, including maternal and newborn healthcare seeking and provision. Yet evidence on mitigation strategies to protect newborn service delivery is limited. We sought to understand what mitigation strategies were employed to protect small and sick newborn care (SSNC) across 65 facilities Kenya, Malawi, Nigeria and Tanzania, implementing with the NEST360 Alliance, and if any could be maintained post-pandemic. METHODS: We used qualitative methods (in-depth interviews n=132, focus group discussions n=15) with purposively sampled neonatal health systems actors in Kenya, Malawi, Nigeria and Tanzania. Data were collected from September 2021 - August 2022. Topic guides were co-developed with key stakeholders and used to gain a detailed understanding of approaches to protect SSNC during the COVID-19 pandemic. Questions explored policy development, collaboration and investments, organisation of care, human resources, and technology and device innovations. Interviews were conducted by experienced qualitative researchers and data were collected until saturation was reached. Interviews were digitally recorded and transcribed verbatim. A common coding framework was developed, and data were coded via NVivo and analysed using a thematic framework approach. FINDINGS: We identified two pathways via which SSNC was strengthened. The first pathway, COVID-19 specific responses with secondary benefit to SSNC included: rapid policy development and adaptation, new and collaborative funding partnerships, improved oxygen systems, strengthened infection prevention and control practices. The second pathway, health system mitigation strategies during the pandemic, included: enhanced information systems, human resource adaptations, service delivery innovations, e.g., telemedicine, community engagement and more emphasis on planned preventive maintenance of devices. Chronic system weaknesses were also identified that limited the sustainability and institutionalisation of actions to protect SSNC. CONCLUSION: Innovations to protect SSNC in response to the COVID-19 pandemic should be maintained to support resilience and high-quality routine SSNC delivery. In particular, allocation of resources to sustain high quality and resilient care practices and address remaining gaps for SSNC is critical.

Isoliquiritigenin ameliorates advanced glycation end-products toxicity on renal proximal tubular epithelial cells.

Diabetic nephropathy is a serious chronic complication affecting at least 25% of diabetic patients. Hyperglycemia associated advanced glycation end-products (AGEs) increase tubular epithelial-myofibroblast transdifferentiation (TEMT) and extracellular matrix synthesis and thereby causes renal fibrosis. The chalcone isoliquiritigenin, found in many herbs of Glycyrrhiza family, is known for potential health-promoting effects. However, their effects on AGE-associated renal proximal tubular fibrosis are not known yet. In this study, the effect of isoliquiritigenin on AGE-induced renal proximal tubular fibrosis was determined in cultured HK-2 cell line. The results show that 200 µg/mL of AGE-induced TEMT and the formed myofibroblasts synthesized collagen to increase extracellular matrix formation thereby lead to renal tubular fibrosis. However, treatment with 200 nM of isoliquiritigenin considerably inhibited the TEMT and suppressed the TGFß/STAT3 mechanism to inhibit collagen secretion. Therefore, isoliquiritigenin effectively suppressed AGE-induced renal tubular fibrosis.

Development of Anti-LRRC15 Small Fragments for Imaging Purposes Using a Phage-Display ScFv Approach.

The human leucine-rich repeat-containing protein 15 (LRRC15) is a membrane protein identified as a marker of CAF (cancer-associated fibroblast) cells whose overexpression is positively correlated with cancer grade and outcome. Nuclear molecular imaging (i.e., SPECT and PET) to track LRRC15 expression could be very useful in guiding further therapeutic strategies. In this study, we developed an ScFv mouse phage-display library to obtain small fragment antibodies against human LRRC15 for molecular imaging purposes. Mice were immunized with recombinant human LRRC15 (hLRRC15), and lymph node cells were harvested for ScFv (single-chain variable fragment) phage-display analysis. The built library was used for panning on cell lines with constitutive or induced expression after transfection. The choice of best candidates was performed by screening various other cell lines, using flow cytometry. The selected candidates were reformatted into Cys-ScFv or Cys-diabody by addition of cysteine, and cloned in mammalian expression vectors to obtain batches of small fragments that were further used in site-specific radiolabeling tests. The obtained library was 1.2 × 107 cfu/µg with an insertion rate >95%. The two panning rounds performed on cells permittedenrichment of 2 × 10−3. Screening with flow cytometry allowed us to identify 28 specific hLRRC15 candidates. Among these, two also recognized murine LRCC15 and were reformatted into Cys-ScFv and Cys-diabody. They were expressed transiently in a mammalian system to obtain 1.0 to 4.5 mg of Cys fragments ready for bioconjugation and radiolabeling. Thus, in this paper, we demonstrate the relevance of the phage-display ScFv library approach for the fast-track development of small antibodies for imaging and/or immunotherapy purposes.

MicroRNA-210 repression facilitates advanced glycation end-product (AGE)-induced cardiac mitochondrial dysfunction and apoptosis via JNK activation.

Hyperglycemia results in the formation of reactive oxygen species which in turn causes advanced glycation end products (AGEs) formation, leading to diabetic cardiomyopathy. Our previous study showed that AGE-induced reactive oxygen species-dependent apoptosis is mediated via protein kinase C delta (PKCδ)-enhanced mitochondrial damage in cardiomyocytes. By using microRNA (miRNA) database, miRNA-210 was predicted to target c-Jun N-terminal kinase (JNK), which were previously identified as downstream of PKCδ in regulating mitochondrial function. Therefore, we hypothesized that miR-210 mediates PKCδ-dependent upregulation of JNK to cause cardiac mitochondrial damage and apoptosis following AGE exposure. AGE-exposed cells showed activated cardiac JNK, PKCδ, and apoptosis, which were reversed by treatment with a JNK inhibitor and PKCδ-KD (deficient kinase). Cardiac miR-210 and mitochondrial function were downregulated following AGE exposure. Furthermore, JNK was upregulated and involved in AGE-induced mitochondrial damage. Interestingly, luciferase activity of the miR-210 mimic plus JNK WT-3'-untranslated region overexpressed group was significantly lower than that of miR-210 mimic plus JNK MT-3'UTR group, indicating that JNK is a target of miR-210. Moreover, JNK activation induced by AGEs was reduced by treatment with the miR-210 mimic and reversed by treatment with the miR-210 inhibitor, indicating the regulatory function of miR-210 in JNK activation following AGE exposure. Additionally, JNK-dependent mitochondrial dysfunction and apoptosis were reversed following treatment with the miR-210 mimic, while the miR-210 inhibitor showed no effect on JNK-induced mitochondrial dysfunction and apoptosis in AGE-exposed cardiac cells. Taken together, our study showed that PKCδ-enhanced JNK-dependent mitochondrial damage is mediated through the reduction of miR-210 in cardiomyocytes following AGE exposure.

Bio-functional properties of probiotic Lactobacillus: current applications and research perspectives.

Lactic acid bacteria as a starter culture are very important component in the fermentation process of dairy and food industry. Application of lactic acid bacteria as probiotic bacteria adds more functionality to the developed product. Gut colonizing bacteria have attractive benefits related to human health. Bio-functional properties such as antimicrobial activity, anti-inflammatory, ACE-inhibitory, antioxidant, antidiarrheal, antiviral, immunomodulatory, hypocholesterolemic, anti-diabetic and anti-cancer activities are the most applicable research areas of lactic acid bacteria. Different strains of Lactobacillus are generally consumed as probiotics and colonize the gastrointestinal tract. Sometimes these bacteria may possess antimicrobial activity and may positively influence the effect of antibiotics. Use of Lactobacillus spp. for the development of functional foods is one of the promising areas of current research and applications. Individual bacterial species have unique biological activity, which may vary from strains to strains and identification of this uniqueness could be helpful in the development of functional and therapeutic food products.

Poria cocos (Fuling) targets TGFß/Smad7 associated collagen accumulation and enhances Nrf2-antioxidant mechanism to exert anti-skin aging effects in human dermal fibroblasts.

Oxidative stress is a major cause of aging related skin injuries. Hydrogen peroxide related ROS accumulation triggers increase in matrix metalloproteinases and elevated collagen degradation, which is a characteristic of skin aging. In this study, we investigated the protective effect of Poria cocos, used widely in the treatment of inflammatory diseases, against H2 O2 induced oxidative stress. The aqueous extract of dried P. cocos was obtained by heating 10 g in 500 ml of distilled water. The mixture was evaporated up to 400 ml and the remaining 100 ml was filtered through muslin cloth repeatedly to obtain a clear aqueous extract of the P. cocos. Hs68 human dermal fibroblast cells were challenged with 100 µM of H2 O2 for 24 h. Following H2 O2 challenge, the cells were treated with increasing concentration of P. cocos extract (100-400 µg/ml) for 24 h. P. cocos extract hindered the H2 O2 induced cell death significantly that was correlated with reduction in ROS accumulation. Western blot analysis show that P. cocos extract suppressed the expression of metallomatrix proteinases, inflammatory markers and skin aging markers, but increased TGF-ß1 levels and antioxidant related proteins. These data suggest that P. cocos is effective in attenuating oxidative stress associated skin aging effects and may be a potential agent in cosmetics products.

Vanillin Production in Pseudomonas: Whole-Genome Sequencing of Pseudomonas sp. Strain 9.1 and Reannotation of Pseudomonas putida CalA as a Vanillin Reductase.

Microbial degradation of lignin and its related aromatic compounds has great potential for the sustainable production of chemicals and bioremediation of contaminated soils. We previously isolated Pseudomonas sp. strain 9.1 from historical waste deposits (forming so-called fiber banks) released from pulp and paper mills along the Baltic Sea coast. The strain accumulated vanillyl alcohol during growth on vanillin, and while reported in other microbes, this phenotype is less common in wild-type pseudomonads. As the reduction of vanillin to vanillyl alcohol is an undesired trait in Pseudomonas strains engineered to accumulate vanillin, connecting the strain 9.1 phenotype with a genotype would increase the fundamental understanding and genetic engineering potential of microbial vanillin metabolism. The genome of Pseudomonas sp. 9.1 was sequenced and assembled. Annotation identified oxidoreductases with homology to Saccharomyces cerevisiae alcohol dehydrogenase ScADH6p, known to reduce vanillin to vanillyl alcohol, in both the 9.1 genome and the model strain Pseudomonas putida KT2440. Recombinant expression of the Pseudomonas sp. 9.1 FEZ21_09870 and P. putida KT2440 PP_2426 (calA) genes in Escherichia coli revealed that these open reading frames encode aldehyde reductases that convert vanillin to vanillyl alcohol, and that P. putida KT2440 PP_3839 encodes a coniferyl alcohol dehydrogenase that oxidizes coniferyl alcohol to coniferyl aldehyde (i.e., the function previously assigned to calA). The deletion of PP_2426 in P. putida GN442 engineered to accumulate vanillin resulted in a decrease in by-product (vanillyl alcohol) yield from 17% to ∼1%. Based on these results, we propose the reannotation of PP_2426 and FEZ21_09870 as areA and PP_3839 as calA-IIIMPORTANCE Valorization of lignocellulose (nonedible plant matter) is of key interest for the sustainable production of chemicals from renewable resources. Lignin, one of the main constituents of lignocellulose, is a heterogeneous aromatic biopolymer that can be chemically depolymerized into a heterogeneous mixture of aromatic building blocks; those can be further converted by certain microbes into value-added aromatic chemicals, e.g., the flavoring agent vanillin. We previously isolated a Pseudomonas sp. strain with the (for the genus) unusual trait of vanillyl alcohol production during growth on vanillin. Whole-genome sequencing of the isolate led to the identification of a vanillin reductase candidate gene whose deletion in a recombinant vanillin-accumulating P. putida strain almost completely alleviated the undesired vanillyl alcohol by-product yield. These results represent an important step toward biotechnological production of vanillin from lignin using bacterial cell factories.

Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes.

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure-activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.

A Promising Family of Fluorescent Water-Soluble aza-BODIPY Dyes for in Vivo Molecular Imaging.

A new family of water-soluble and bioconjugatable aza-BODIPY fluorophores was designed and synthesized using a boron- functionalization strategy. These dissymmetric bis-ammonium aza-BODIPY dyes present optimal properties for a fluorescent probe; i.e., they are highly water-soluble, very stable in physiological medium; they do not aggregate in PBS, possess high quantum yield; and finally, they can be easily bioconjugated to antibodies. Preliminary in vitro and in vivo studies were performed for one of these fluorophores to image PD-L1 (Programmed Death-Ligand 1), highlighting the high potential of these new probes for future in vivo optical imaging studies.

Hepatitis C virus core protein interacts with cellular metastasis suppressor Nm23-H1 and promotes cell migration and invasion.

Hepatitis C virus (HCV) is the major etiological agent of hepatocellular carcinoma (HCC), which is the fourth most common cause of cancer-related deaths worldwide and second in terms of deaths of males (Bray et al. in CA Cancer J Clin 68(6):394-424, 2018). HCV-induced HCC is a multi-step process that involves alteration of several host regulatory pathways. One of the key features of HCV-associated hepatocellular carcinoma is the metastasis of cancer cells to different organs. Human Nm23-H1 is one of the best-studied metastasis suppressor proteins, and it has been shown to be modulated in many human cancers. Our study shows that the core protein of HCV genotype 2a can co-localize and interact directly with Nm23-H1 within cancer cells, resulting in modulation of the anti-metastasis properties of Nm23-H1. The HCV core protein promotes SUMOylation and degradation of the Nm23-H1 protein, as well as transcriptional downregulation. This study provides evidence that the HCV core protein is a pro-metastatic protein that can interact directly with and modulate the functions of cellular metastasis suppressor Nm23-H1.

Luminometric Label Array for Counting and Differentiation of Bacteria.

Methods for simple and fast detection and differentiation of bacterial species are required, for instance, in medicine, water quality monitoring, and the food industry. Here, we have developed a novel label array method for the counting and differentiation of bacterial species. This method is based on the nonspecific interactions of multiple unstable lanthanide chelates and selected chemicals within the sample leading to a luminescence signal profile that is unique to the bacterial species. It is simple, cost-effective, and/or user-friendly compared to many existing methods, such as plate counts on selective media, automatic (hemocytometer-based) cell counters, flow cytometry, and polymerase chain reaction (PCR)-based methods for identification. The performance of the method was demonstrated with nine single strains of bacteria in pure culture. The limit of detection for counting was below 1000 bacteria per mL, with an average coefficient of variation of 10% achieved with the developed label array. A predictive model was trained with the measured luminescence signals and its ability to differentiate all tested bacterial species from each other, including members of the same genus Bacillus licheniformis and Bacillus subtilis, was confirmed via leave-one-out cross-validation. The suitability of the method for analysis of mixtures of bacterial species was shown with ternary mixtures of Bacillus licheniformis, Escherichia coli JM109, and Lactobacillus reuteri ATCC PTA 4659. The potential future application of the method could be monitoring for contamination in pure cultures; analysis of mixed bacterial cultures, where examining one species in the presence of another could inform industrial microbial processes; and the analysis of bacterial biofilms, where nonspecific methods based on physical and chemical characteristics are required instead of methods specific to individual bacterial species.

Precision medicine in breast cancer: reality or utopia?

Many cancers, including breast cancer, have demonstrated prognosis and support advantages thanks to the discovery of targeted therapies. The advent of these new approaches marked the rise of precision medicine, which leads to improve the diagnosis, prognosis and treatment of cancer. Precision medicine takes into account the molecular and biological specificities of the patient and their tumors that will influence the treatment determined by physicians. This new era of medicine is accessible through molecular genetics platforms, the development of high-speed sequencers and means of analysis of these data. Despite the spectacular results in the treatment of cancers including breast cancer, described in this review, not all patients however can benefit from this new strategy. This seems to be related to the many genetic mutations, which may be different from one patient to another or within the same patient. It comes to give new impetus to the research-both from a technological and biological point of view-to make the hope of precision medicine accessible to all.

Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.

BACKGROUND: The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. METHODS: Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity. RESULTS: T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p < 0.0001) is significantly higher than in invasive bladder tumors and in patients with high-grade bladder carcinoma, respectively. In addition, heavy smokers, whose tumors express low levels of GATA-3 and Bcl-6, are poor responders to BCG (p = 0.01 and p = 0.03). Finally, better patient survival correlated with GATA-3 (p = 0.04) and Bcl-6 (p = 0.04) but not T-bet expression. CONCLUSIONS: Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.

Gold-phosphine-porphyrin as potential metal-based theranostics.

Two new gold-phosphine-porphyrin derivatives were synthesized and fully characterized, and their photophysical properties investigated along a water-soluble analog. The cytotoxicity of the compounds was tested on cancer cells (HCT116 and SW480), and their cell uptake was followed by fluorescence microscopy in vitro (on SW480). The proof that the water-soluble gold-phosphine-porphyrin is a biologically active compound that can be tracked in vitro was clearly established, especially concerning the water-soluble analog. Some preliminary photodynamic therapy (PDT) experiments were also performed. They highlight a dramatic increase of the cytotoxicity when the cells were illuminated for 30 min with white light.

A GH57 4-α-glucanotransferase of hyperthermophilic origin with potential for alkyl glycoside production.

4-α-Glucanotransferase (GTase) enzymes (EC 2.4.1.25) modulate the size of α-glucans by cleaving and reforming α-1,4 glycosidic bonds in α-glucans, an essential process in starch and glycogen metabolism in plants and microorganisms. The glycoside hydrolase family 57 enzyme (GTase57) studied in the current work catalyzes both disproportionation and cyclization reactions. Amylose was converted into cyclic amylose (with a minimum size of 17 glucose monomers) as well as to a spectrum of maltodextrins, but in contrast to glycoside hydrolase family 13 cyclodextrin glucanotransferases (CGTases), no production of cyclodextrins (C6-C8) was observed. GTase57 also effectively produced alkyl-glycosides with long α-glucan chains from dodecyl-ß-D-maltoside and starch, demonstrating the potential of the enzyme to produce novel variants of surfactants. Importantly, the GTase57 has excellent thermostability with a maximal activity at 95 °C and an activity half-life of 150 min at 90 °C which is highly advantageous in this manufacturing process suggesting that enzymes from this relatively uncharacterized family, GH57, can be powerful biocatalysts for the production of large head group glucosides from soluble starch.

Comparison of the In Vitro and In Vivo Behavior of a Series of NIR-II-Emitting Aza-BODIPYs Containing Different Water-Solubilizing Groups and Their Trastuzumab Antibody Conjugates.

The development of new fluorescent organic probes effective in the NIR-II region is currently a fast-growing field and represents a challenge in the domain of medical imaging. In this study, we have designed and synthesized an innovative series of aza-boron dipyrromethenes emitting in the NIR-II region. We have investigated the effect of different water-solubilizing groups not only on the photophysical properties of the compounds but also on their in vitro and in vivo performance after bioconjugation to the antibody trastuzumab. Remarkably, we discovered that the most lipophilic compound unexpectedly displayed the most favorable in vivo properties after bioconjugation. This underlines the profound influence that the fluorophore functionalization approach can have on the efficiency of the resulting imaging agent.