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Purpose: PREF-NET reported patients' experience of Somatuline® (lanreotide) Autogel® (LAN) administration at home and in hospital among patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)., Methods: PREF-NET was a multicentre, cross-sectional study of UK adults (aged ≥ 18 years) with GEP-NETs receiving a stable dose of LAN, which comprised of (1) a quantitative online survey, and (2) qualitative semi-structured interviews conducted with a subgroup of survey respondents. The primary objective was the description of overall patient preference for home versus hospital administration of LAN. Secondary objectives included describing patient-reported opinions on the experience and associated preference for each administration setting, and the impact on healthcare utilisation, societal cost, activities of daily living and health-related quality of life (HRQoL)., Results: In the primary analysis (80 patients; mean age 63.9 years), 98.7% (95% confidence interval [CI]: 96.1-100.0) of patients preferred to receive LAN at home, compared with 1.3% (95% CI: 0.0-3.9) who preferred the hospital setting. Among participants, over half (60.3%) received their injection from a non-healthcare professional. Most patients (79.5% [95% CI: 70.5-88.4]) reported a positive effect on HRQoL after the switch from hospital to home administration. Qualitative interviews (20 patients; mean age 63.6 years) highlighted that patients preferred home administration because it improved overall convenience; saved time and costs; made them feel more comfortable and relaxed, and less stressed; and increased confidence in their ability to self-manage their treatment., Conclusion: Almost all patients preferred to receive LAN treatment at home rather than in hospital with increased convenience and psychological benefits reported as key reasons for this preference., (© 2024. The Author(s).)

The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant Candida auris , and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of Candida species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.

In this research, a sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent-based capsule phase microextraction (CPME) device was developed in combination with liquid chromatography-post column derivatization for the first ever reported determination of a somatostatin analogue - lanreotide in human urine. The sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent was encapsulated in the lumen of a polypropylene capillary tube and characterized by FT-IR spectroscopy and SEM with energy dispersive X-ray spectroscopy (EDS). The main steps of the CPME workflow were optimized to obtain high extraction efficiency for the target analyte. After the separation of the analyte on a C 8 stationary phase, the peptide was derivatized online with o-phthalaldehyde before the fluorescence detection. The main experimental parameters of CPME and the post-column procedures were systematically investigated and optimized. The method was validated in terms of selectivity, linearity, accuracy, precision, limits of detection (LOD), and limits of quantification (LOQ). The relative bias ranged between 88.8 and 115.6 % for the peptide, while the RSD values for repeatability and intermediate precision were less than 14.3 %. The achieved limit of detection (LOD) was 0.2 μΜ while the limit of quantitation (LOQ) was established as 0.9 μΜ. Finally, the sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent-based microextraction capsules were found to be reusable for at least 20 extractions. The developed method presented adequate overall performance, and it could be applied in the analysis of selected peptide in human urine samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two different types of arthritis. Within RA, the subsets between seronegative RA (snRA) and seropositive RA (spRA) represent distinct disease entities; however, identifying clear distinguishing markers between them remains a challenge. This study investigated and compared the oral health conditions in patients with RA and OA to clarify the differences from healthy controls. In addition, we investigated the serological characteristics of the patients, the factors that distinguished patients with RA from those with OA, and the main factors that differentiated between snRA and spRA patients. A total of 161 participants (mean age: 52.52 ± 14.57 years, 32 males and 129 females) were enrolled in this study and categorized as: normal (n = 33), OA (n = 31), and RA (n = 97). Patients with RA were divided into the following two subtypes: snRA (n = 18) and spRA (n = 79). Demographics, oral health, and serological characteristics of these patients were compared. The prevalence of periodontal diseases was significantly higher in patients with OA (100%) and RA (92.8%) than in healthy controls (0.0%). However, the presence of periodontal diseases was not utilized as a distinguishing factor between OA and RA. Xerostomia occurred more frequently in patients with RA (84.5%) than in patients with OA (3.2%) and healthy controls (0.0%) (all p < 0.001). ROC analysis revealed that periodontal disease was a very strong predictor in the diagnosis of OA compared to healthy controls, with an AUC value of 1.00 (p < 0.001). Additionally, halitosis (AUC = 0.746, 95% CI 0.621-0.871, p < 0.001) and female sex (AUC = 0.663, 95% CI 0.529-0.797, p < 0.05) were also significant predictors of OA. The strongest predictors of RA diagnosis compared to healthy controls were periodontal diseases (AUC = 0.964), followed by xerostomia (AUC = 0.923), age (AUC = 0.923), female sex (AUC = 0.660), and halitosis (AUC = 0.615) (all p < 0.05). Significant serological predictors of RA were anti-CCP Ab (AUC = 0.808), and RF (AUC = 0.746) (all p < 0.05). In multiple logistic regression analysis, xerostomia (odds ratio, OR: 8124.88, 95% CI 10.37-6368261.97, p-value = 0.008) and Anti-CCP Ab (OR: 671.33, 95% CI 2.18-207,074.02, p = 0.026) were significant predictors for RA compared to OA. When diagnosing spRA compared to snRA, anti-CCP Ab (AUC = 1.000, p < 0.001) and RF (AUC = 0.910, 95%CI 0.854-0.967, p < 0.001) had outstanding predictive performances. Therefore, clinicians and researchers should thoroughly evaluate the oral status of both OA and RA patients, alongside serological factors, and consider these elements as potential predictors., (© 2024. The Author(s).)

We previously reported that acid-degradable methylated β-cyclodextrins (Me-β-CDs)-threaded polyrotaxanes (Me-PRXs) can induce autophagic cell death through endoplasmic reticulum (ER) stress-related autophagy, even in apoptosis-resistant cells. Hence, Me-PRXs show great potential as anticancer therapeutics. In this study, peptide-supermolecule conjugates were designed to achieve the targeted delivery of Me-PRX to malignant tumors. Arg-Gly-Asp peptides are well-known binding motifs of integrin α v β 3 , which is overexpressed on angiogenic sites and many malignant tumors. The tumor-targeted cyclic Arg-Gly-Asp (cRGD) peptide was orthogonally post-modified to Me-PRX via click chemistry. Surface plasmon resonance (SPR) results indicated that cRGD-Me-PRX strongly binds to integrin α v β 3 , whereas non-targeted cyclic Arg-Ala-Glu (cRGE) peptide conjugated to Me-PRX (cRGE-Me-PRX) failed to interact with integrins α v β 3 . In vitro, cRGD-Me-PRX demonstrated enhanced cellular internalization and antitumor activity in 4T1 cells than that of unmodified Me-PRX and non-targeted cRGE-Me-PRX, due to its ability to recognize integrin α v β 3 . Furthermore, cRGD-Me-PRX accumulated effectively in tumors, leading to antitumor effects, and exhibited excellent biocompatibility and safety in vivo. Therefore, cRGD conjugation to enhance selectivity for integrin α v β 3 -positive cancer cells is a promising design strategy for Me-PRXs in antitumor therapy.

Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis., Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide version 2 (anti-CCP2) and 16 individual antibodies against citrullinated protein (ACPA) reactivities were analysed centrally in baseline sera from 1600 patients with RA classified according to the 1987 American College of Rheumatology (ACR) criteria. These results were related to C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), number of swollen and tender joints (SJC and TJC), 28-joint disease activity scores (DAS28 and DAS28CRP), global disease activity evaluated by the patients and Health Assessment Questionnaire, all obtained at baseline., Results: Individually, all autoantibodies except immunoglobulin G (IgG) RF associated with low SJC and TJC and with high ESR. In IgM RF-negative patients, ACPA associated strictly with low number of swollen and tender joints. This association persisted in multiple regression and stratified analyses where IgM and IgA RF instead associated with inflammation expressed as ESR. Among subjects without any ACPA peptide reactivity, there was no association between RF isotypes and ESR. The effect of RF on ESR increased with the number of ACPA reactivities, especially for IgM RF. In patients fulfilling the 1987 ACR criteria without taking RF into account, associations between IgM RF and high ESR, as well as between ACPA and low joint counts, remained., Conclusion: Whereas ACPA associate with low counts of affected joints in early RA, RF associates with elevated measures of systemic inflammation in an ACPA-dependent manner. This latter finding corroborates in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria., Competing Interests: Competing interests: EP and LM-A are employees at Thermo Fisher Scientific. JA has had or have research agreements with AbbVie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis and Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS). JR has been a member of the Scientific Advisory Board for Thermo Fisher Scientific and for Inova/Werfen and has received consulting fees, speaking fees and/ or honoraria by Thermo Fisher Scientific. RH has received consulting fees from Regor, Lipum AB and Cyxone AB and is the founder of Vacara AB. LK has been a co-ordinator of several IMI-funded projects which included collaborations with Janssen, Pfizer, Sanofi, UCB, GSK and Eli-Lilly. This work has been presented as a poster in a preliminary form at EULAR (June 2019) and to the European Workshop for Rheumatology Research (March 2023)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the diagnostic efficiency and prognostic value of 68 Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis., Methods: We prospectively recruited 26 patients diagnosed with PA. All patients underwent 68 Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4., Results: On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2., Conclusion: Our analysis showed that 68 Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68 Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yin, Ai, Luo, Liu, Ma, Zhou, Xiang, Su, Wang and Li.)

Metastasis is one of the major causes of death in patients with cancer, and cell invasion plays a fundamental part in this process. Because of the absence of efficacious treatments, caring for these patients is challenging. Recently, we optimized the structure of the naturally occurring lasso peptide sungsanpin. We identified two peptides, octapeptide S3 and cyclic peptide S4, which inhibited invasion into A549 cells effectively. We undertook an alanine scan of S3 to explore the structure-activity relationship. The linear octapeptide S3-4 and cyclic peptide S4-1 exhibited improved inhibition of invasion into A549 cells. We modified S3-4 to obtain S3-4K, which displayed much higher inhibitory activity against invasion into A549 cells than S3-4. Of all peptides tested, S4-1 upregulated significantly mRNA of tissue inhibitor matrix metalloproteinase TIMP-1 and TIMP-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Recent advances imply that early events triggering rheumatoid arthritis (RA) occur at mucosal surfaces. We aimed to evaluate whether intestinal permeability is altered in patients at increased risk of RA, and/or predicts the development of clinical arthritis, by measuring serum zonulin family peptides (ZFP) levels, which are shown to reflect intestinal barrier integrity., Methods: Two independent prospective observational cohorts were studied, including subjects with musculoskeletal symptoms and anticitrullinated protein antibodies (ACPA), but without clinical arthritis at baseline. In Sweden, 82 such at-risk patients were compared to 100 age-matched healthy blood donors. In the UK, 307 at-risk patients were compared to 100 ACPA-negative symptomatic controls. ZFP was measured in baseline sera by enzyme-linked immunoassays., Results: In the Swedish at-risk cohort, ZFP levels were significantly increased in patients compared to controls (mean 41.4 vs 33.6 ng/mL, P < 0.001) and Cox regression analysis showed prognostic value of ZFP for arthritis development (hazard ratio [HZ] 1.04 per ng/mL ZFP increase, 95% CI 1.01-1.07, P = 0.02). Elevated ZFP levels among ACPA-positive at-risk patients compared to symptomatic ACPA-negative controls were confirmed in the UK at-risk cohort (mean 69.7 vs 36.0 ng/mL, P < 0.001), but baseline ZFP were not associated with arthritis development (HR 1.00 per ng/mL ZFP increase, 95% CI 1.00-1.01, P = 0.30)., Conclusion: Serum ZFP levels are elevated in ACPA-positive at-risk patients when compared to both healthy blood donors and symptomatic ACPA-negative controls. Thus, gut barrier function may be of importance in RA-associated autoimmunity. A possible prognostic value of serum ZFP merits further investigation, preferably in larger prospective cohorts., (Copyright © 2024 by the Journal of Rheumatology.)

Ten-Eleven Translocation (TET) enzymes are Fe(II)/2OG-dependent oxygenases that play important roles in epigenetic regulation, but selective inhibition of the TETs is an unmet challenge. We describe the profiling of previously identified TET1-binding macrocyclic peptides. TiP1 is established as a potent TET1 inhibitor (IC 50  = 0.26 µM) with excellent selectivity over other TETs and 2OG oxygenases. TiP1 alanine scanning reveals the critical roles of Trp10 and Glu11 residues for inhibition of TET isoenzymes. The results highlight the utility of the RaPID method to identify potent enzyme inhibitors with selectivity over closely related paralogues. The structure-activity relationship data generated herein may find utility in the development of chemical probes for the TETs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that influenced the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with marginal zone lymphoma (MZL), [ 18 F]FDG PET/CT provided inconsistent diagnostic accuracy. C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in MZL and thus, may emerge as novel theranostic target. We aimed to evaluate the diagnostic performance of CXCR4-targeting [ 68 Ga]Ga-PentixaFor when compared to [ 18 F]FDG PET/CT in MZL., Methods: Thirty-two untreated MZL patients (nodal, n = 17; extranodal, n = 13; splenic, n = 2) received [ 68 Ga]Ga-PentixaFor and [ 18 F]FDG PET/CT within median 2 days. We performed a visual and quantitative analysis of the total lymphoma volume by measuring maximum/peak standardized uptake values (SUV max/peak ), and calculating target-to-background ratios (TBR, defined as lesion-based SUV peak divided by SUV mean from blood pool). Visual comparisons for both radiotracers were carried out for all target lesions (TL), and quantitative analysis of concordant TL evident on both scans. Last, MZL subtype analyses were also conducted., Results: On a patient-based level, [ 68 Ga]Ga-PentixaFor identified MZL manifestations in 32 (100%) subjects (vs. [ 18 F]FDG, 25/32 [78.1%]). Of the 256 identified TL, 127/256 (49.6%) manifestations were evident only on CXCR4-directed imaging, while only 7/256 (2.7%) were identified on [ 18 F]FDG but missed by [ 68 Ga]Ga-PentixaFor. In the remaining 122/256 (47.7%) concordant TL, [ 68 Ga]Ga-PentixaFor consistently provided increased metrics when compared to [ 18 F]FDG: SUV max , 10.3 (range, 2.53-37.2) vs. 5.72 (2.32-37.0); SUV peak , 6.23 (1.58-25.7) vs. 3.87 (1.54-27.7); P < 0.01, respectively. Concordant TL TBR on [ 68 Ga]Ga-PentixaFor (median, 3.85; range, 1.05-16.0) was also approximately 1.8-fold higher relative to [ 18 F]FDG (median, 2.08; range, 0.81-28.8; P < 0.01). Those findings on image contrast, however, were driven by nodal MZL (P < 0.01), and just missed significance for extranodal MZL (P = 0.06)., Conclusions: In newly diagnosed MZL patients, [ 68 Ga]Ga-PentixaFor identified more sites of disease when compared to [ 18 F]FDG, irrespective of MZL subtype. Quantitative PET parameters including TBR were also higher on [ 68 Ga]Ga-PentixaFor PET/CT, suggesting improved diagnostic read-out using chemokine receptor-targeted imaging., (© 2023. The Author(s).)

Carbonyl-carbonyl interactions in peptides and proteins attracted considerable interest in recent years. Here, we report a survey of carbonyl-carbonyl interactions in cyclic peptides, depsipeptides, peptoids and discuss the relationship between backbone torsion angles and CO∙∙∙CO distances. In general, φ values in the range between -40° and -90° and between 40° and 90° correspond to CO∙∙∙CO distances below 3.22 Å. By extending the analysis of carbonyl-carbonyl interactions in different types of beta turns in proteins, we also highlight the role of direct or reciprocal carbonyl-carbonyl interactions in stabilizing the beta turn conformation for each specific type. We confirmed the new type II beta turn, detected by Dunbrack and coworkers, and named Pa, and detect the presence of a direct carbonyl-carbonyl interaction between the second and third residues of the turn. We also evidenced the existence of another new type II beta turn, named pA (following Dunbrack's notation), which represents the alternative conformation of Pa with opposite φ and ψ values and is characterized by a direct carbonyl-carbonyl interaction between the second and third residues of the turn. Finally, we show that the occurrence of CO∙∙∙CO interactions could be also advocated to explain from a chemical point of view the diversity of turn types., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Purpose: PRESTO 3 evaluated nurses' preference for the Somatuline® Autogel® syringe versus the Lanreotide Pharmathen syringe after injection-pad testing., Methods: This international simulated-use study included oncology/endocrinology nurses with ≥ 1 years' experience in managing neuroendocrine tumours (NETs) and/or acromegaly. Each nurse tested both syringes twice in a randomised order before completing an electronic survey. The primary objective was to assess overall preference (%, 95% confidence interval [CI]) for the Somatuline Autogel syringe versus the Lanreotide Pharmathen syringe. Secondary objectives included rating syringe performance and ranking the importance of syringe attributes., Results: Ninety-four nurses were enrolled: mean age, 41.0 (SD, 11.5) years. The percentage of nurses stating a preference ("strong" or "slight") for the Somatuline Autogel syringe (86.2% [95% CI 77.5-92.4%]) was significantly higher than 50% (p < 0.0001). Performance rating was significantly higher for the Somatuline Autogel syringe versus Lanreotide Pharmathen syringe for 10 of the 11 attributes tested (p < 0.05). The syringe attributes considered most important when injecting patients in routine clinical practice were "easy to use from preparation to injection" (30.9%) and "comfortable to handle during use from preparation to injection" (16.0%). The attribute most commonly rated as least important was "fast administration from preparation to injection" (26.6%)., Conclusion: Nurses strongly preferred the user experience of the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. "Ease of use" and "comfortable to handle" were the most important syringe attributes, and performance rating was significantly higher with Somatuline Autogel versus Lanreotide Pharmathen syringe for all but one attribute., (© 2023. The Author(s).)

Aspergillus flavus produces hepatocarcinogenic aflatoxin that adversely impacts human and animal health and international trade. A promising means to manage preharvest aflatoxin contamination of crops is biological control, which employs non-aflatoxigenic A. flavus isolates possessing defective aflatoxin gene clusters to outcompete field toxigenic populations. However, these isolates often produce other toxic metabolites. The CRISPR/Cas9 technology has greatly advanced genome editing and gene functional studies. Its use in deleting large chromosomal segments of filamentous fungi is rarely reported. A system of dual CRISPR/Cas9 combined with a 60-nucleotide donor DNA that allowed removal of A. flavus gene clusters involved in production of harmful specialized metabolites was established. It efficiently deleted a 102-kb segment containing both aflatoxin and cyclopiazonic acid gene clusters from toxigenic A. flavus morphotypes, L-type and S-type. It further deleted the 27-kb ustiloxin B gene cluster of a resulting L-type mutant. Overall efficiencies of deletion ranged from 66.6 % to 85.6 % and efficiencies of deletions repaired by a single copy of donor DNA ranged from 50.5 % to 72.7 %. To determine the capacity of this technique, a pigment-screening setup based on absence of aspergillic acid gene cluster was devised. Chromosomal segments of 201 kb and 301 kb were deleted with efficiencies of 57.7 % to 69.2 %, respectively. This system used natural A. flavus isolates as recipients, eliminated a forced-recycling step to produce recipients for next round deletion, and generated maker-free deletants with sequences predefined by donor DNA. The research provides a method for creating genuine atoxigenic biocontrol strains friendly for field trial release., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The structural modeling of peptides can be a useful aid in the discovery of new drugs and a deeper understanding of the molecular mechanisms of life. Here we present a novel multiscale protocol for the structure prediction of linear and cyclic peptides. The protocol combines two main stages: coarse-grained simulations using the CABS-flex standalone package and an all-atom reconstruction-optimization process using the Modeller program. We evaluated the protocol on a set of linear peptides and two sets of cyclic peptides, with cyclization through the backbone and disulfide bonds. A comparison with other state-of-the-art tools (APPTEST, PEP-FOLD, ESMFold and AlphaFold implementation in ColabFold) shows that for most cases, AlphaFold offers the highest resolution. However, CABS-flex is competitive, particularly when it comes to short linear peptides. As demonstrated, the protocol performance can be further improved by combination with the residue-residue contact prediction method or more efficient scoring. The protocol is included in the CABS-flex standalone package along with online documentation to aid users in predicting the structure of peptides and mini-proteins., (© The Author(s) 2024. Published by Oxford University Press.)

Lipopeptides, derived from microorganisms, are promising surface-active compounds known as biosurfactants. However, the high production costs of biosurfactants, associated with expensive culture media and purification processes, limit widespread industrial application. To enhance the sustainability of biosurfactant production, researchers have explored cost-effective substrates. In this study, crude glycerol was evaluated as a promising and economical carbon source in viscosinamide production by Pseudomonas fluorescens DR54. Optimization studies using the Box - Behnken design and response surface methodology were performed. Optimal conditions for viscosinamide production including glycerol 70.8 g/L, leucine 2.7 g/L, phosphate 3.7 g/L, and urea 9.3 g/L were identified. Yield of viscosinamide production, performed under optimal conditions, reached 7.18 ± 0.17 g/L. Preliminary characterization of viscosinamide involved the measurement of surface tension. The critical micelle concentration of lipopeptide was determined to be 5 mg/L. Furthermore, the interactions between the viscosinamide and lipase from Candida rugosa (CRL) were investigated by evaluating the impact of viscosinamide on lipase activity and measuring circular dichroism. It was observed that the α-helicity of CRL increases with increasing viscosinamide concentration, while the random coil structure decreases., (© 2024. The Author(s).)

Balgacyclamide A-C are a family of cyanobactin natural products isolated from freshwater cyanobacteria Microcystis aeruginosa. These macrocyclic peptides are characterized by their oxazoline-thiazole core, their 7 or 8 stereocenters, and their antiparasitic activities. Balgacyclamide B is known for its activity towards Plasmodium falciparum chloroquine-resistant strain K1, Trypanosoma brucei rhodesiense, and Leishmania donovani. In this report, the first total synthesis of Balgacyclamide B is described in a 17-steps pathway and a 2 % overall yield. The synthetic pathway toward balgacyclamide B can be adapted for the future syntheses of balgacyclamide A and C. In addition, a brief history background of oxazolines syntheses is shown to emphasize the importance of the cyclization conditions used to interconvert or retain configuration of β-hydroxy amides via dehydrative cyclization., (© 2023 Wiley-VCH GmbH.)

Background: Over-activation of endometrial inflammasome NALP-3 (Nod-like receptor family pyrin domain containing 3) can be found in recurrent pregnancy loss (RPL) women probably due to leaky gut and passage into circulation of lipopolysaccharides (LPS). Leaky gut can be caused by exposure to gluten in RPL women genetically predisposed to celiac disease, positive for Human Leukocyte Antigen (HLA)-DQ2/DQ8 haplotype. Oral administration of Bifidobacterium longum ES1 (GliadinES®) can inactivate gluten peptides toxicity to epithelial gut cells and improve gut barrier., Methods: We investigated by enzyme-linked immunoassay: (a) serum levels of LPS and zonuline (a marker of leaky gut); (b) LPS, NALP-3, caspase-1, interleukine (IL)-1β and IL-18 concentration in endometrial fluids, in untreated women with uncomplicated pregnancies (negative HLA-DQ2/DQ8 haplotype) (n = 22) and in women with unexplained RPL, HLA-DQ2/DQ8 positive (n = 22), before and after daily oral administration for 3 months of GliadinES®., Results: RLP women showed higher serum levels of LPS (p < 0.0001) and higher concentration of LPS (p < 0.0001), NALP-3 (p < 0.01); Caspase-1 (p < 0.0001), IL-1β (p < 0.0001), and IL-18 (p < 0.0001) in endometrial fluids compared to controls. GliadinES® treatment significantly reduced serum levels of both LPS (p < 0.0001) and zonuline (p < 0.01), as well as LPS (p < 0.5), NALP-3 (p < 0.01), Caspase-1 (p < 0.001), IL-1β (p < 0.001), and IL-18 (p < 0.01) concentrations in endometrial fluids of RPL women., Conclusions: RPL women positive for HLA-DQ2/DQ8 haplotype show increased circulating and endometrial levels of LPS and endometrial inflammasome NALP-3 over-activation. Oral administration of GliadinES® can reduce gut permeability, decrease serum levels of LPS and, contextually, improve endometrial inflammation in this specific subset of RPL women., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current classification criteria for rheumatoid arthritis (RA) encompass clinical and immunological items and are capable of correctly identifying the majority of symptomatic RA patients. The presence of positive rheumatoid factor (RF) and/or and anti-cyclic citrullinated protein/peptide antibodies (ACPA) gaining increasing importance according to their serological titer eases the recognition of RA, yet the debate is open on whether this scoring system ought to be optimized by hierarchizing ACPA or the combination of ACPA and RF over single positivity, prioritizing specificity over sensitivity. The risk of misdiagnosis and misclassification are often entangled, yet they are not the same. In fact, while ideal diagnosis requires 100% sensitivity and specificity, classification criteria are conceived to gather a homogeneous patient population, favoring specificity over sensitivity. Nevertheless, as they are frequently summoned to support the diagnostic process in clinical practice, issues arise on how comprehensive those should be and on how frequently they should be updated in light of novel acquisitions regarding measurable RA-related abnormalities. In this viewpoint two different views on the topic are confronted, discussing the performance of available criteria and the potentiality and pitfalls of their refinement according to novel data on ACPA and RF contribution and emergence of newly discovered specificities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Interteaching is a behavioral teaching method that has demonstrated efficacy in higher education. Of particular interest is the use of a preparation guide (a guided reading assignment), which is designed to promote engagement in the other areas of the interteaching process. The present study compared the use of a preparation guide completed before the start of class with that of a quiz administered at the start of the class. The quiz was hypothesized to serve as a functional alternative to the preparation guide. A total of 38 undergraduate students enrolled in an Introduction to Psychology course participated in this study. The primary dependent measure was student performance on tests following each condition. The analysis revealed no statistically significant difference between the conditions, F(1, 302) = 0.103, p = .748, though qualitative feedback revealed student preference for preparation guides. Future research is necessary to examine the effects of quizzing while addressing the limitations of this study., (© 2023 Society for the Experimental Analysis of Behavior (SEAB).)