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Il contributo analizza la funzione del codice bucolico, tra forma classica e magma biografico e storico che vi sotteso, a partire da "Bucolicum carmen" del Petrarca.

Il contributo analizza lo stretto rapporto tra parole e immagine, filologia e iconografia nelle forme dell'enciclopedismo umanistico bolognese, con particolare riferimento ai sistemi del commento e alle Symbolicae Quaestiones di Achille Bocchi

Il contributo presenta il prosieguo, nei "Sermones V-VIII, dell'edizione moderna, della traduzione e del commento dei testi del grande umanista bolognese.

Background Fanconi anemia (FA) is a rare disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer. Patients harboring X‐linked FANCB pathogenic variants usually present with severe congenital malformations resembling VACTERL syndrome with hydrocephalus. Methods We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection of duplication, targeted capture and next‐gen sequencing for defining the duplication breakpoint, PacBio sequencing of full‐length FANCB aberrant transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of FANCB protein function by viral transduction of FANCB‐null cells with lentiviral FANCB WT and mutant expression constructs, and droplet digital PCR for quantitation of the duplication in the genomic DNA and cDNA. Results We describe here an FA‐B patient with a mild phenotype. The DEB diagnostic test for FA revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in FANCB, covering the first coding exon 3 and the flanking regions. A four bp homology (GTAG) present at both ends of the breakpoint is consistent with microhomology‐mediated duplication mechanism. The duplicated allele gives rise to an aberrant transcript containing exon 3 duplication, predicted to introduce a stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient fibroblasts have shown 8% of wild‐type (WT) allele and his carrier mother showed higher than expected levels of WT allele (79% vs. 50%) in peripheral blood, suggesting that the duplication was highly unstable. Conclusion Unlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA‐B patient described here.

DOI: 10.11855/j.issn.0577-7402.2017.11.01

The Advanced Ion Source for Hadrontherapy (AISHa) has been designed to generate high brightness multiply charged ion beams for hadron therapy applications. AISHa is a compact electron cyclotron resonance ion source whose hybrid magnetic system consists of a permanent Halbach-type hexapole magnet and a set of independently energized superconducting coils. This has allowed us to achieve high performances in a cost effective way. During the commissioning phase, a few criticalities have been observed and fixed in 2018/19; the improvements will be briefly described and the results of the operations with a single 18 GHz generator will be presented. Particular relevance will be given to the production of high intensity beams of oxygen, argon, and carbon, the latter having huge importance for hadron therapy applications. Perspectives for further improvements, including double frequency heating, will also be highlighted.

Denosumab is associated with continued gains in hip and spine BMD with up to 10 years of treatment in postmenopausal women with osteoporosis. Despite potent inhibition of bone remodeling, findings in nonhuman primates suggest modeling-based bone formation (MBBF) may persist during denosumab treatment. This study assessed whether MBBF in the femoral neck (FN) is preserved in the context of inhibited remodeling in subjects receiving denosumab. This open-label study enrolled postmenopausal women with osteoporosis who had received two or more doses of denosumab (60 mg subcutaneously every 6 months [Q6M]) per standard of care and were planning elective total hip replacement (THR) owing to osteoarthritis of the hip. Transverse sections of the FN were obtained after THR and analyzed histomorphometrically. MBBF, based on fluorochrome labeling and presence of smooth cement lines, was evaluated in cancellous, endocortical, and periosteal envelopes of the FN. Histomorphometric parameters were used to assess MBBF and remodeling-based bone formation (RBBF) in denosumab-treated subjects (n = 4; mean age = 73.5 years; range, 70 to 78 years) and historical female controls (n = 11; mean age = 67.8 years; range, 62 to 80 years) obtained from the placebo group of a prior study and not treated with denosumab. All analyses were descriptive. All subjects in both groups exhibited MBBF in the periosteal envelope; in cancellous and endocortical envelopes, all denosumab-treated subjects and 81.8% of controls showed evidence of MBBF. Compared with controls, denosumab-treated subjects showed 9.4-fold and 2.0-fold higher mean values of MBBF in cancellous and endocortical envelopes, respectively, whereas RBBF mean values were 5.0-fold and 5.3-fold lower. In the periosteal envelope, MBBF and RBBF rates were similar between subjects and controls. These results demonstrate the occurrence of MBBF in the human FN and suggest that denosumab preserves MBBF while inhibiting remodeling, which may contribute to the observed continued gains in BMD over time after remodeling is maximally inhibited. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

DNA-encoded compound libraries are widely used in drug discovery. Screening of catalysts for compatibility with solid phase-coupled DNA sequences guided the selection of encoded reactions, exemplified by a Zn(II)-mediated aza-Diels–Alder reaction., DNA-encoded compound libraries are a widely used technology for target-based small molecule screening. Generally, these libraries are synthesized by solution phase combinatorial chemistry requiring aqueous solvent mixtures and reactions that are orthogonal to DNA reactivity. Initiating library synthesis with readily available controlled pore glass-coupled DNA barcodes benefits from enhanced DNA stability due to nucleobase protection and choice of dry organic solvents for encoded compound synthesis. We screened the compatibility of solid-phase coupled DNA sequences with 53 metal salts and organic reagents. This screening experiment suggests design of encoded library synthesis. Here, we show the reaction optimization and scope of three sp3-bond containing heterocyclic scaffolds synthesized on controlled pore glass-connected DNA sequences. A ZnCl2-promoted aza-Diels–Alder reaction with Danishefsky's diene furnished diverse substituted DNA-tagged pyridones, and a phosphoric acid organocatalyst allowed for synthesis of tetrahydroquinolines by the Povarov reaction and pyrimidinones by the Biginelli reaction, respectively. These three reactions caused low levels of DNA depurination and cover broad and only partially overlapping chemical space though using one set of DNA-coupled starting materials.

Context There are few studies on patients transitioning from denosumab to bisphosphonates. Objective To investigate patient characteristics and changes in bone mineral density (BMD) after transitioning from denosumab to alendronate. Design Randomized, open-label, 2-year crossover Denosumab Adherence Preference Satisfaction (DAPS) study (NCT00518531). Setting 25 study centers in the US and Canada. Patients Treatment-naïve postmenopausal women with BMD T-scores from −2.0 to −4.0. Interventions This post hoc analysis evaluated women randomized to subcutaneous denosumab 60 mg every 6 months in year 1 followed by once-weekly oral alendronate 70 mg in year 2. Main Outcome Measure A 3% BMD threshold identified participants who lost, maintained, or gained BMD in year 2 on alendronate. Results Of 126 participants randomized to denosumab, 115 (91%) transitioned to alendronate in year 2. BMD increased by 3% to 6% with denosumab in year 1 and by 0% to 1% with alendronate in year 2. After transitioning to alendronate, most participants maintained or increased BMD; 15.9%, 7.6%, and 21.7% lost BMD at the lumbar spine, total hip, and femoral neck, respectively. Few participants fell below their pretreatment baseline BMD value; this occurred most often in those who lost BMD in year 2. Women who lost BMD with alendronate in year 2 also showed a greater percent change in BMD with denosumab in year 1. The BMD change in year 2 was similar regardless of baseline characteristics or adherence to oral alendronate. Conclusion Alendronate can effectively maintain the BMD gains accrued after 1 year of denosumab in most patients, regardless of baseline characteristics.

Peptidylglycine α-amidating monooxygenase (PAM) catalyses the amidation of glycine-extended peptides, thereby maximising their biological potency. We recently showed that coding alleles in PAM mediate type 2 diabetes (T2D) risk through alterations to PAM protein activity and expression in the β cell. Identifying alleles along a continuum of functional severity informs on the relationship between protein perturbation and clinical effect. We hypothesised that rare, loss of function PAM alleles could cause severe β cell dysfunction presenting as neonatal diabetes. Sequencing of 15 probands presenting with diabetes at ≤ 6 months of age and their unaffected immediate family, identified a novel de novo nonsynonymous coding variant (p.R36S) in PAM in a single proband. We investigated the impact of the variant allele on amidating activity, protein stability and localisation as a measure of PAM function and the consequences on β cell viability. Recombinant R36S-PAM exhibited normal amidating activity in vitro which was consistent with PAM activity measured in patient serum (WT: 391pmol/μl/hr vs. R36S: 305pmol/μl/hr). In human β cells (EndoC-βh1) the secreted luminal R36S-PAM isoform displayed reduced protein expression (-78%, p=0.004) compared to WT-PAM, which could be rescued by inhibiting the proteosomal pathway (+120% of WT); whilst the non-secreted membrane-integral isoform was retained in the endoplasmic reticulum (ER). We observed that overexpression of R36S-PAM elevated levels of ER stress (p-IRE1: +196%, p=0.02; CHOP: +114%, p=0.051) and pro-apoptotic markers (ASK1: +145%, caspase-3: +154%) compared with WT-PAM. We have identified a novel, de novo coding variant, in a gene with a proven role in T2D risk, in a single patient with neonatal diabetes. Functional studies provide evidence for protein mislocalisation and instability and support a role for this allele in ER stress and β cell dysfunction consistent with neonatal diabetes pathogenesis. Disclosure S. Sengupta: None. L.L. Bonnycastle: None. B. Hastoy: None. A. Grotz: None. M.M. Umapathysivam: None. A. Raimondo: None. A. Swift: None. P.S. Chines: None. A. Clark: None. H. Huopio: None. F.S. Collins: None. M. Laakso: None. A.L. Gloyn: Consultant; Spouse/Partner; Eli Lilly and Company, Merck & Co., Inc. Consultant; Self; Merck & Co., Inc. Consultant; Spouse/Partner; Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Diabetes UK, European Foundation for the Study of Diabetes. Funding UK Wellcome Trust

Significance Identifying causal relationships within a web of human genotype–phenotype correlations is a substantial challenge. Using the largest genetic study to date of comeasured expression and DNA methylation (DNAme) in skeletal muscle, we identify correlations among expression, DNAme, and physiological traits. Leveraging Mendelian randomization (MR) and mediation techniques, we identify 213 putative causal relationships between expression and DNAme. We further use MR to prioritize hundreds of genes and thousands of DNAme sites that may drive genetic associations for diseases and quantitative traits. Our study integrates genetic, diverse -omics, and physiological measurements—a challenge of increasing importance in the field of human genomics., We integrate comeasured gene expression and DNA methylation (DNAme) in 265 human skeletal muscle biopsies from the FUSION study with >7 million genetic variants and eight physiological traits: height, waist, weight, waist–hip ratio, body mass index, fasting serum insulin, fasting plasma glucose, and type 2 diabetes. We find hundreds of genes and DNAme sites associated with fasting insulin, waist, and body mass index, as well as thousands of DNAme sites associated with gene expression (eQTM). We find that controlling for heterogeneity in tissue/muscle fiber type reduces the number of physiological trait associations, and that long-range eQTMs (>1 Mb) are reduced when controlling for tissue/muscle fiber type or latent factors. We map genetic regulators (quantitative trait loci; QTLs) of expression (eQTLs) and DNAme (mQTLs). Using Mendelian randomization (MR) and mediation techniques, we leverage these genetic maps to predict 213 causal relationships between expression and DNAme, approximately two-thirds of which predict methylation to causally influence expression. We use MR to integrate FUSION mQTLs, FUSION eQTLs, and GTEx eQTLs for 48 tissues with genetic associations for 534 diseases and quantitative traits. We identify hundreds of genes and thousands of DNAme sites that may drive the reported disease/quantitative trait genetic associations. We identify 300 gene expression MR associations that are present in both FUSION and GTEx skeletal muscle and that show stronger evidence of MR association in skeletal muscle than other tissues, which may partially reflect differences in power across tissues. As one example, we find that increased RXRA muscle expression may decrease lean tissue mass.

Polyhydroxyalkanoates (PHAs) are considerable biopolymers that have gained an increasing biotechnological interest in different applications, although their industrial production presents several limitations. Filamentous bacterial cells could represent a possible strategy to increase PHA yield, since more abundant PHA inclusions can be stored in elongated than in rod-shaped cells. At first, we determined the optimal batch culture conditions to induce filamentation in Pseudomonas mediterranea CFBP-5447T, using glutamine, glycerol, glucose, and sodium octanoate, as the sole carbon source, at low- (100 rpm) or high- (250 rpm) shaking speeds. Successively, a fermentative process was set up using glutamine in a co-metabolic strategy with glycerol, and the PHAs production was compared in rod-shaped and filamentous cells. High glutamine concentrations (from 28 to 56 mM) were able to induce alone filamentation, whereas at lower glutamine concentrations (5-10 mM), the shaking speeds became critical to allow or not filamentous phenotype. PHA granule production was higher in filamentous than in rod-shaped cells, when glycerol (46.6 mM) was added to glutamine (5 mM) in co-metabolism, and fermentation was performed at a low-shaking speed. After extraction and precipitation, PHA yield was about two times higher in filamentous than that rod-shaped cells. Our results provide new insights into filament-inducing conditions and indicate a potential use of filamentous P. mediterranea CFBP-5447T cells to increase PHA yield. These findings could have great advantages in PHAs recovering during downstream processes, since the harvesting of elongated cells is much less time-consuming and energy expensive than required with rod-shaped cells.

The AISHa ion source has been designed to generate high brightness multiply charged ion beams with high reliability, easy operations and maintenance for hadrontheraphy applications. Aisha is a compact ECRIS whose hybrid magnetic system consists of a permanent Halbach-type hexapole magnet and a set of independently energized superconducting He-free coils. The present work shows the results of the ion source commissioning in SFH operational mode (18 GHz) for different ion species. Current status and further improvements will be highlighted., Proceedings of the 23th Int. Workshop on ECR Ion Sources, ECRIS2018, Catania, Italy

Il contributo esami i rapporti culturali, finora non adeuatamente indagati, tra gli esponenti più significativi dell'umanesimo bolognese (Beroaldo, Codro) e la grande lezione del Mirandolano.

Nowadays, urban areas play a crucial role in biodiversity conservation and habitat protection despite the constant pressures on which these habitats are subjected. They may even host relatively new plant communities due to the peculiar ecosystem where they vegetate. The port of Trieste (NE Italy) is characterized by a mixed mosaic of intensely human impacted areas (where commercial activities are still ongoing) flanked by abandoned areas where vegetation persists or has spontaneously recovered. In this study, we sampled the whole port area through a stratified random sampling by placing multiscalar nested plots in four different habitats (strata) previously identified by photo-interpretation. Plant species richness and abundance were assessed in each plot. Each species was then classified as native or alien and patterns of species richness and complementarity were compared among habitats. Results show that there is a significant difference in species richness patterns among habitats, while observed patterns are likely to vary at different spatial scales. As expected, urban plots account for most of the alien species in the sampling, while wooded plots cope better with invasion, accounting for a lower alien/native ratio. These results highlight how habitat diversity enhances biodiversity in urban areas and how it could provide an effective filtering effect able to reduce the spread of alien species. In addition, we provide further evidence for the use of multi-scale approaches in order to study the complex relationships between spatial heterogeneity and plant species richness.

Si illustrano la figura e il magistero del lavoro critico di Gian Mario Anselmi e le linee guida che hanno condotto all'allestimento del volume.

Nel contributo si segue la diversa evoluzione che nella scrittura dantesca e petrarchesca assume un testo dello Pseudoseneca di grande rilievo nella cultura letteraria del Trecento.

The aim of this contribution is to attribute to Ludovico Ariosto the authorship of a drawing that was found on the cover of his « Registro dei Conti dei Balestrieri ». The « Registro » is currently stored in the Modena State. The research was based on paleographic analyses and documentary studies, which suggest a possible interpretation of such a drawing.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. METHODS AND RESULTS: We report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide-one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T>A mutation in blood DNA and a c.1968+2T>C in DNA from cultured fibroblasts. Deep sequencing of DNA from the proband's blood revealed 4.7% c.1968+2T>C mutation, and 41.3% c.1968+2T>A mutation. CONCLUSIONS: We hypothesise that the germline mutation was c.1968+2T>A, but a rescue event occurred during early development, where the somatic mutation from A to C at 1968+2 provided a selective advantage. This type of mosaicism where a partial phenotypic rescue event results from a second but milder disease-causing mutation in the same nucleotide has not been previously characterised for any disease.

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Background:Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women. Since bisphosphonates are generally contraindicated in patients with estimated glomerular filtration rate (eGFR) Objectives:To determine if baseline renal function affects the efficacy and safety of romosozumab.Methods:We performed post hoc analyses of two clinical trials of romosozumab in postmenopausal women with osteoporosis. In ARCH (NCT01631214), 4,093 patients were randomised 1:1 to romosozumab 210 mg monthly or alendronate 70 mg weekly for 12 months (mean age: 74.3 years; 96.1% with prevalent vertebral fractures [VFx]). In FRAME (NCT01575834), 7,180 patients were randomised 1:1 to romosozumab 210 mg or placebo monthly for 12 months (mean age: 70.9 years; 18.3% with prevalent VFx). For these analyses, patients were categorised by baseline eGFR (mL/min/1.73m2): normal renal function (eGFR ≥90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). Least squares mean (LSM) percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck; incidence of new VFx and adverse events (AEs); and changes in renal function were assessed for each eGFR category at Month 12 of the double-blind treatment period.Results:At baseline, most patients had mild/moderate renal insufficiency: 84% in ARCH, 88% in FRAME. In both studies, change from baseline in BMD was significantly higher in the romosozumab group across baseline eGFR categories (Figure). There was an interaction between BMD increase and renal function, and although BMD increase was not as large in women with impaired renal function, differences between romosozumab and control groups remained significant (Figure). In ARCH, among patients with eGFR ≥90, 60–89, and 30–59, the incidence of new VFx (romosozumab vs alendronate) at Month 12 was 3.3% vs 7.3%, 3.2% vs 3.9%, and 3.4% vs 6.2% in ARCH. In FRAME, the incidence of new VFx (romosozumab vs placebo) at Month 12 was 0.5% vs 3.0%, 0.4% vs 1.5%, and 0.6% vs 2.1%.In both studies, the incidences of AEs and serious AEs were similar in both treatment groups within and across eGFR categories. AEs of mild-to-moderate hypocalcaemia (investigator reported) occurred in two patients in ARCH (one romosozumab [eGFR 60–89] and one alendronate [eGFR ≥90]), and one patient in FRAME (romosozumab [eGFR 60–89]). Five patients in ARCH (all in the alendronate group) and 19 patients in FRAME (14 romosozumab, 5 placebo) had decreases in serum Ca levels (albumin adjusted); in the romosozumab group all were mild (Conclusion:The efficacy and safety of romosozumab vs alendronate or placebo was similar among postmenopausal women with osteoporosis and different levels of renal function.Acknowledgments:This study was funded by Amgen, Astellas and UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Paul Miller Grant/research support from: Amgen, Radius Health, Ultragenyx, Consultant of: Amgen, Radius Health, Jonathan Adachi Consultant of: Amgen, Speakers bureau: Amgen, Ben-Hur Albergaria Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Angela M Cheung Consultant of: Amgen, Eli Lilly, Arkadi Chines Shareholder of: Amgen Inc., Employee of: Amgen Inc., Evelien Gielen Consultant of: Amgen Inc., Takeda, Sandoz and UCB Pharma, Speakers bureau: Amgen Inc., Takeda, Sandoz and UCB Pharma, Bente Langdahl Grant/research support from: Amgen, NovoNordisk, Consultant of: Amgen Inc., Eli Lilly, UCB Pharma, Akimitsu Miyauchi Consultant of: Amgen Inc., Astellas BioPharma K.K., Teijin Pharma, Mary Oates Shareholder of: Amgen Inc., Employee of: Amgen Inc., Ian Reid Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Norma Ruiz Santiago Shareholder of: Amgen Inc., Employee of: Amgen Inc., Mark Vanderkelen Employee of: UCB Pharma, Wenjing Yang Shareholder of: Amgen Inc., Employee of: Amgen Inc., Zhigang Yu Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Purpose Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. Methods Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. Results Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07–0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00–3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [ 1 ]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. Conclusion Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.

DNA-encoded libraries of organic, synthesized molecules are an emerging technology for target-based compound screening. The design of first generation encoded libraries placed emphasis on ever increasing compound numbers that were synthesized from large sets of starting materials with a few well-established synthesis methods. In the last two years there has literally been an explosion of published research activities that have expanded the toolbox of reactions for designing DNA-encoded libraries. In this digest, we highlight latest developments that include modern photoredox chemistries as well as strategies to perform encoded compound synthesis in organic solvents or exploit nano-heterogeneous systems. The new chemistry developments carry the potential to revolutionize the technology as they enable access to unprecedented molecular diversity.