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461 papers

Intestinal microbiota profile and inflammation in patients undergoing hemodialysis: a comparison between the Southern and Southeastern regions of Brazil.

Paiva BR et al. · Jul 1, 2026

Introduction Exogenous lifestyle factors, such as different cultures, diets, and geo-graphic location, can alter the microbiota in patients with chronic kidney disease (CKD), which is closely related to inflammation. However, few studies have examined how these factors influence the composition of the microbiota. Thus, the objective of this study was to characterize and compare the intestinal microbiota profile and inflammation in CKD patients undergoing hemodialysis (HD) in the Southern and Southeastern regions of Brazil. Methods Blood and stool samples were obtained from two groups of HD patients: one from the city of Blumenau (Southern region) and the other from the city of Rio de Janeiro (Southeastern region). Fecal DNA was extracted, and the V4 region of the bacterial 16S ribosomal RNA gene was sequenced. The fecal microbiome was analyzed using bioinformatic tools. Plasma concentrations of IL-6 and TNF-α were evaluated by ELISA. Results Thirty patients were included in the study, with 14 individuals residing in the Southern region (group S) [50% male, 58 (13.5) years of age] and 16 individuals residing in the Southeastern region (group SE) [47.1% male, 57 (19) years of age]. The α- and β-diversity indices of the intestinal microbiota did not differ significantly between the groups. However, patients from the Southern region had higher plasma TNF-α (p = 0.008) and IL-6 (p = 0.003) levels than those from the Southeastern region. Conclusion Although HD patients with CKD residing in the Southern and Southeastern regions present similar intestinal microbial patterns, patients from the Southern region had higher concentrations of inflammatory markers.

Biochemistry, Genetics and Molecular Biology

Fine structural tuning of the assembly of elastin-collagen peptide conjugates with drug loading and manipulation of molecular interactions.

Huang H et al. · Jul 1, 2026

Elastin-collagen nanoparticles (ECnPs) have been shown in our previous studies to self-assemble into different morphologies, including nanoplates and nanovesicles, by manipulating the sequence length of the elastin-like peptide (ELPs) and collagen-like peptide (CLPs) of a given conjugate. In this work, we demonstrate that the morphologies of ECnPs can also be modulated, for a given ECnP sequence, with variations in solution pH and/or the amount of encapsulated drug. Specifically, the peptide (VPGYG) 6 -(GPO) 8 preferentially formed nanovesicles under basic conditions but assembled into nanoplates under acidic conditions. Another sequence, (VPGWG) 2 (VPGFG) 2 -(GPO) 8 , produced nanovesicles when loaded with a high concentration of dexamethasone-carboxyfluorescein (Dex-CF), but transitioned to nanoplates at lower drug loading. Furthermore, in addition to the different morphologies observed for a given set of initial solution conditions, our studies also illustrate the possibility of triggering vesicle-to-plate transformations for a given ECnP with release of Dex-CF over time. These results highlight multiple avenues for controlling ECnP morphology, expanding their applicability as a flexible and efficient drug delivery platform.

Biochemistry, Genetics and Molecular Biology

Ruminants Epidemiology, Spatial Clustering and Multivariate Risk Modelling of Cutaneous Leishmaniasis in District Bajaur, Pakistan.

Khan MA et al. · Jul 1, 2026

Background and objective Cutaneous leishmaniasis (CL) remains a significant public health concern in endemic regions of Pakistan, particularly in ecologically diverse and resource-limited areas. This study aimed to investigate the epidemiology, risk factors, lesion characteristics, seasonal trends and spatial distribution of CL in District Bajaur, Khyber Pakhtunkhwa, Pakistan. Methods A cross-sectional observational study was conducted in 2022, including clinically suspected and laboratory-confirmed CL cases from all nine tehsils of District Bajaur. Demographic information, lesion characteristics (site, type and number), season of presentation and regional distribution were collected using a structured questionnaire. Statistical analyses included univariate and multivariate logistic regression, multinomial regression, Poisson regression, stratified analyses and interaction modelling. Spatial clustering was evaluated using Z-scores, Moran's I statistics and GIS-based risk mapping. Results CL prevalence was significantly higher among males, younger individuals, unmarried participants and during the summer season. Lesions were predominantly located on exposed body parts, especially the hands and face, with dry lesions and single-lesion presentations being most common. Multivariate analysis identified male gender, younger age, unmarried status, summer season, dry lesion type and single lesions as independent risk factors. Stratified and interaction analyses indicated an elevated risk among young males during the summer. Spatial analysis revealed significant clustering of cases, with Khar, Loe Mamund and Salarzai identified as high-risk tehsils. A clinician-friendly risk scoring system was developed to estimate individual infection probability. Conclusion CL in District Bajaur is influenced by a complex interaction of demographic, clinical, seasonal and spatial factors. These findings emphasize the importance of targeted surveillance, vector control strategies and risk-based interventions to reduce disease burden in endemic regions.

Medicine

Human umbilical cord mesenchymal stromal cell-derived exosomes from MSCs pretreated with inflammatory factors attenuate renal injury of diabetic mice by regulating macrophage polarization.

Li C et al. · Jul 1, 2026

Diabetic nephropathy (DN), a major complication of diabetes mellitus (DM), is characterized by severe clinical manifestations, impaired quality of life, and a high risk of progression to end-stage renal disease, underscoring the urgent need for effective therapeutic interventions. Mesenchymal stromal cell-derived exosomes (MSC-Exo) have emerged as promising candidates for mitigating inflammatory injury in DN due to their immunomodulatory properties, and exosomes derived from MSCs pretreated with inflammatory factors such as TNF-α and IFN-γ may possess enhanced therapeutic potential. In this study, exosomes isolated from human umbilical cord MSCs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Their therapeutic effects were evaluated in diabetic mice, focusing on renal inflammation and macrophage polarization. Both normal MSC-Exo (Norm-Exo) and TNF-α&IFN-γ-pretreated MSC-Exo (TNF-α&IFN-γ-Exo) effectively ameliorated kidney injury and promoted M2 macrophage polarization, with TNF-α&IFN-γ-Exo showing superior efficacy. High-glucose-stimulated RAW264.7 cells were used to explore the underlying mechanisms, and high-throughput RNA sequencing identified inhibitor of DNA binding 3 (ID3) as a molecule involved in MSC-Exo-regulated macrophage polarization. Loss-of-function experiments confirmed that ID3 knockdown alone recapitulated the effects of exosomes, promoting M2 polarization and suppressing M1 markers. Conversely, ID3 overexpression attenuated exosome efficacy. Mechanistically, ID3 partially mediated exosome-induced inhibition of the NF-κB pathway. The translational relevance of these findings was further validated in PMA-differentiated THP-1 human macrophages. Collectively, these findings demonstrate that MSC-Exo-particularly TNF-α&IFN-γ-Exo-attenuate diabetic renal injury by modulating macrophage polarization through ID3 regulation, highlighting a novel cell-free immunomodulatory approach for DN therapy.

Biochemistry, Genetics and Molecular Biology

A Systematic Review and Expert Evaluation of Perioperative SGLT2 Inhibitor-Associated Ketoacidosis Case Reports.

Snel LIP et al. · Jul 1, 2026

Introduction The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the perioperative setting may lead to SGLT2i-associated postoperative ketoacidosis (SAPKA) in patients with type 2 diabetes (T2D). Therefore, cessation of this drug is recommended before surgery. We aimed to study reported cases to assess the causality of SGLT2i, identify common characteristics, potential risk factors, treatment and outcomes of SAPKA. Methods We conducted a systematic literature search to identify case reports of patients with metabolic acidosis and the presence of ketones who used SGLT2i in the perioperative setting. Case reports were summarised for common characteristics, assessed for quality and distributed to a panel of diabetes experts, who evaluated the likelihood of SAPKA using a questionnaire. Results Ninety-three papers containing 128 case reports fulfilled the inclusion criteria. The expert panel found SAPKA to be 'likely' in 53 (41%), 'possible' in 38 (30%) and 'unlikely' in 27 (21%) cases; 10 cases (8%) could not be validated due to insufficient data or implausible timing. SAPKA was therefore considered likely or possible in 71% (91/128) of cases. Common factors identified in the SAPKA reports included a diagnosis of T2D mellitus (n = 115), impaired perioperative intake (n = 30) and insufficient insulin supplementation (n = 10). Treatment with insulin was effective, and ketoacidosis resolved in all surviving patients, although significant morbidity, including ICU admission, was reported in a substantial proportion of cases. Discussion Confirming a SAPKA diagnosis is challenging due to the variable reporting quality and numerous confounding factors present during the perioperative period. Clinicians should remain aware of SAPKA given the increasing prevalence of SGLT2i use. Focusing on early recognition and treatment represents a potential alternative strategy to routine preoperative SGLT2i discontinuation, though this requires further prospective evaluation. Editorial comment This systematic review presents an overview and discussion of the many, to date, case reports of ketoacidosis thought to be associated with perioperative SGLT2 inhibitor treatment.

Medicine

Sex-specific differences in serum phosphate persist in patients with CKD.

Schatz M et al. · Jul 1, 2026

Introduction Phosphate plays a critical role in numerous metabolic processes, and sex-specific differences have been identified in its concentrations in the general population. However, such differences have not been investigated in the context of CKD, in which additional factors may exert a more pronounced impact on these levels. Methods This retrospective study was conducted in an outpatient nephrology clinic and included data from 632 patients with CKD stages 1-5. Results Serum phosphate was negatively associated with age (r = -0.08; p = 0.04) and estimated glomerular filtration rate (eGFR) (r = -0.23; p Conclusion Even in the presence of CKD, women have higher serum phosphate (P) levels than men. This sex difference should be considered in the management of CKD-mineral and bone disorder (CKD-MBD).

Medicine

Photocross-linking activity-based probes to capture the dynamics of ubiquitin RING E3 ligase interactions.

Chandler SF et al. · Jul 1, 2026

Almost all cellular processes are influenced by ubiquitination. A large family of enzymes known as E3 ligases provides the specificity for ubiquitination, with the largest class among them, the Really Interesting New Gene (RING) E3s, comprising over 600 members in humans. RING E3s facilitate transfer of ubiquitin (Ub) to substrates by constraining the highly dynamic E2-Ub thioester linkage to be primed for attack from the substrate nucleophile. We have established a workflow that uses an N-maleimido diazirine (NMD) photoactivatable cross-linker attached to ubiquitin that, once stably linked to the active site of an E2, creates an activity-based probe (ABP) to monitor interactions with E3 ligases. Cross-linking mass spectrometry using the NMD-Ub-E2 ABP identified regions of interaction between ubiquitin and a selection of different RING E3s, which not only agreed with existing crystal structures, but was also used to evaluate in silico structural models of complexes yet to be resolved by conventional means. The cross-linking data also provided insight into domains of conformational flexibility which likely adopt multiple configurations in solution and which are challenging to monitor by other methods. NMD-Ub-E2 ABPs offer great potential to explore the ensemble conformations of E2-E3 complexes in solution and have scope for applications beyond the ubiquitin system.

Biochemistry, Genetics and Molecular Biology

Assessing the Psychometric Properties of the Child Behaviour Checklist in the ABCD Study.

Pavlovich K et al. · Jul 1, 2026

The Child Behaviour Checklist (CBCL) is a widely used measure of psychopathology in developmental research and serves as the primary measure in the landmark Adolescent Brain Cognitive Development study (N = 11,861; 8-11 years). However, its psychometric properties in this sample have not been assessed in detail. Analyses using a multi-method framework (CFA, B-CFA, FMM, IRT, ESEM) indicate that a commonly used bifactor structure of the CBCL does not fit the data and instead the scale can be adequately described as unidimensional. Moreover, seven of eight subscales demonstrate insufficient construct validity and are not valid indicators of any higher-order models. All exhibit poor measurement precision below the mean of the latent traits, and item-level exploratory methods produce unstable factors with weak discriminant validity. These findings suggest caution in using the CBCL for dimensional measurement in this dataset and highlight the need for measures explicitly developed and validated for dimensional psychopathology in population-scale research. SUMMARY: The CBCL is a widely used measure of child and adolescent psychopathology, but its psychometric properties in the ABCD study cohort remain unclear. Using a multi-method approach we show that the CBCL is unidimensional and is not well represented by the commonly used bifactor model. CBCL subscales demonstrate insufficient construct validity and demonstrate poor measurement precision across the latent trait continuum. In combination, our findings caution against the use of the CBCL for dimensional measurement of developmental psychopathology in the ABCD study cohort.

Decision Sciences

Effects of Green Tea Extract and (+)-Catechin Hydrate on Sperm Quality and Seminal Plasma Antioxidant Activity: An In Vitro Study in Rams.

Nabhani R et al. · Jul 1, 2026

Background Antioxidants have gained significant attention for improving sperm parameters. Green tea and catechin, known for their potent antioxidant properties, are particularly interesting in this context. Objective This study investigated the in vitro effects of green tea extract (GTE) and (+)-catechin on semen quality parameters of Arabi rams during chilled storage. Methods The pooled and diluted semen was divided and supplemented with GTE and (+)-catechin (50, 100, 150 and 200 µg/mL levels). The control group did not receive any supplements. Sperm quality and semen pH were evaluated at 1, 24, 48 and 72 h after storage. Seminal plasma MDA level was measured at 72 h of semen storage. Results Supplementation with GTE and (+)-catechin improved sperm motility more than control (p Conclusions GTE and catechin enhance semen parameters during chilled storage, with optimal effects at specific concentrations. High levels of GTE may negatively impact sperm quality, underscoring the importance of precise dosing in semen preservation.

Medicine

Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.

Hammoum T et al. · Jul 1, 2026

Peptide-based nanoparticles (PBN) have emerged as a promising alternative to lipid nanoparticles (LNP) for nucleic acid delivery and efficient cellular uptake. In this study, we evaluated the formulation of WRAP5 (W- and R-rich amphipathic peptide 5)-based PBN using a microfluidic device and assessed the impact of key process parameters, flow rate ratio (FRR), total flow rate (TFR), and mixing channel design, on nanoparticle characteristics. Across 72 formulations encapsulating small interfering RNA (siRNA) or plasmid DNA (pDNA), dynamic light scattering revealed consistent mean sizes ranging from 50 to 70 nm, with a low polydispersity index (PdI < 0.22), independent of FRR, TFR, or mixer type. Stability studies demonstrated that siRNA-loaded PBN exhibited moderate size increases during storage at 4°C, whereas pDNA-loaded PBN remained highly stable for up to 70 days. Biological assays confirmed robust activity: WRAP5:siRNA PBN achieved approximately 50% CDK4 silencing in GIST-T1 cells, and WRAP5:pDNA PBN mediated efficient mCHERRY expression in HeLa cells, regardless of formulation method or storage duration. These findings highlight the robustness and scalability of WRAP5-based PBN, contrasting with LNP systems that require stringent control of FRR and TFR, and partially underscore their potential for nucleic acid delivery applications.

Biochemistry, Genetics and Molecular Biology