Conectar
This study aimed to systematically delineate the clinical characteristics and identify the key risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) infections in burn patients, thereby informing targeted preventive measures and therapeutic strategies. This retrospective study included 270 burn patients with Staphylococcus aureus (S. aureus) infections at a Chinese centre (2019–2022), comprising 127 MRSA and 143 methicillin-susceptible S. aureus (MSSA) cases. Clinical data were analysed to assess infection profiles, resistance patterns and MRSA risk factors. Amongst the infections, 68.1% (184/270) were caused by multi-drug resistant S. aureus, specifically 47.0% (127/270) by MRSA and 21.1% (57/270) by MSSA. The predominant resistance pattern (penicillin, oxacillin, gentamicin, clindamycin, erythromycin, ciprofloxacin, levofloxacin, tetracycline) accounted for 23.9% (44/184) of multidrug-resistant cases. The overall MRSA detection rate was 47.0% (127/270). Univariate analysis identified multiple factors significantly associated with MRSA infection (p < 0.05). Multivariate analysis identified the use of ≥ 3 types of antibiotics as an independent risk factor for MRSA infection in burn wounds. The detection rate of multi-drug resistant S. aureus (including MRSA) infections in burn wounds is relatively high. A number of variables are the influencing factors for MRSA infections. Medical personnel should adopt infection control measures to block the transmission of multi-drug resistant bacteria (including MRSA).
Compression therapy is the evidence-based treatment for healing venous leg ulcers. However, it is not routinely applied in many UK hospitals. This paper explores hospital staff's' perspectives of venous leg ulcer care provision where compression therapy is not routinely applied. A semi-structured interview study was conducted with 11 participants, drawn from a larger study, who confirmed that their respective hospitals did not apply compression therapy to inpatients with venous leg ulcers. The interviews were analysed using reflexive thematic analysis. Findings indicate that venous leg ulcer care in hospitals was de-prioritised, which, along with structural and organisational constraints, affected clinicians' engagement and focus on it in their hospitals. This de-prioritisation also led to a lack of formal leg ulcer training in hospitals. However, some clinicians showed remarkable empathy for patients derived from their clinical professionalism and deep understanding of their suffering. To help hospital clinicians and senior managers prioritise venous leg ulcer care, it is crucial to first understand their clinical practise priorities. Secondly, understanding how some hospitals implement compression therapy could be beneficial for those where it is not routine practise. Further research should focus on better understanding clinicians and senior managers' clinical priorities and the structural and organisational constraints in real-world settings, ideally in hospitals where compression therapy is a routine practise. Most importantly, the study highlighted key questions for hospital leaders and policymakers: consider fostering the established clinicians' empathy before it is too late.
by Abdulmujeeb Opeyemi Muhammad-Olodo, Laura Asher
IntroductionHuman papillomavirus (HPV) vaccine prevents over 90% of cervical cancers. In October 2023, Nigeria launched a free HPV vaccination campaign targeting girls aged 9–14 years. Despite removing cost barriers, misinformation about fertility impacts and population control contributed to variable uptake across states. Understanding caregiver decision-making is crucial for improving coverage. This study aimed to explore factors influencing caregivers’ HPV vaccination decisions during Nigeria’s 2023 campaign in Ilorin East Local Government Area, Kwara State.
MethodsA qualitative study using focus group discussions (FGDs) was conducted using purposive and snowball sampling. We recruited 41 caregivers (mean age 47 years; 71% female) of eligible girls from urban and rural communities. Five FGDs were conducted: four with vaccine acceptors (n = 35) and one with decliners (n = 6). Discussions were conducted in Yoruba, audio-recorded, transcribed verbatim, and analysed using Braun and Clarke’s reflexive thematic analysis. Ethical approval was obtained from two institutional review boards.
ResultsFour themes emerged from the analysis. Trust operated at multiple levels: institutional (government programmes), interpersonal (healthcare worker competence), and community (religious/traditional leader endorsement). Historical medical mistrust, intensified by COVID-19 experiences, may have manifested as fertility and population control fears. Personal cancer experiences strongly motivated acceptance, whilst concerns about childhood sexuality influenced timing preferences. Despite free provision, barriers included geographic inequities (remote Fulani-Hausa communities were excluded), language barriers (no Hausa translators), school-based delivery gaps, and indirect costs (transport, time). Caregivers recommended house-to-house campaigns, multilingual services, traditional leader engagement, and permanent vaccination centres.
ConclusionFree vaccine provision is necessary but not sufficient to ensure uptake. Successful HPV vaccination requires rebuilding trust through community engagement, addressing historical medical exploitation concerns, and ensuring equitable access. Integrating these findings into Nigeria’s National Programme on Immunisation could improve coverage from current estimates of 54% to targeted 90%, protecting more girls from cervical cancer whilst respecting community values.
by Karin Törnbom, Dominique Hange, Eva-Lisa Petersson, Irene Svenningsson
BackgroundDespite increasing attention to youth mental health, children and adolescents in Sweden experience fragmented, inequitable care with regional variation. Delays in diagnosis, limited preventive interventions, and poor inter-sectoral collaboration contribute to significant unmet needs. This study investigates system-level challenges and stakeholder perspectives on opportunities to enhance care pathways.
MethodsWe conducted a qualitative study in the Västra Götaland region, Sweden. Fourteen purposively selected participants – including senior executives, healthcare professionals, and parents took part in semi-structured interviews. We used systematic text condensation, according to Malterud, and the four steps involved in this method for analysing the interviews.
ResultsA central theme across interviews was the requirement for a formal diagnosis before children can access mental health support, particularly in school and primary care settings. Participants described this as a major barrier that delays early intervention and leaves children and young people with complex or atypical presentations without adequate support. Primary care professionals reported increasing mental health caseloads without corresponding increases in staffing or funding, limiting preventive work. Child and adolescent psychiatry (BUP) was described as overwhelmed, with long waiting times and limited continuity of care. A care manager within primary care was proposed as a way to help families navigate fragmented services and improve collaboration, although participants emphasised that such a role would need to be part of broader structural reform.
ConclusionsOur findings highlight persistent systemic issues in mental health care for children and young people, including inequitable access, insufficient prevention, and fragmented collaboration across sectors. Strengthening primary prevention, reallocating resources to primary and school-based mental health care and implementing well-defined care coordination roles within broader restructuring may improve continuity and equity in service delivery. Comprehensive policy reform is needed to support person-centred, integrated care pathways for children and young people with mental health needs.
by Sevilay Gülesen, Victoria Most, Clara T. Schoeder, Jens Meiler
Viruses such as coronaviruses or filoviruses use their surface glycoproteins (GPs) to attach to the host cell, triggering the fusion of the viral membrane with the endosome membrane. Epitopes on the viral GP are major targets for antibody-mediated recognition and neutralization. During the fusion process, the GP undergoes conformational changes triggered by fluctuations in environmental pH. Structural states are typically classified into three distinct conformations: prefusion, intermediate, and postfusion. These conformations serve as essential templates for prediction of conformational epitopes and structure-based vaccine design. Despite their importance, many viral GP structures remain absent from the Protein Data Bank (PDB). Fortunately, recent breakthroughs in computational structure prediction have greatly enhanced the accuracy and accessibility of protein modeling. In this study, we utilized AlphaFold2-Multimer (AF2-M), version 2.3, to predict various GP structural conformations and observed that the overall frequency of predictions in the postfusion conformation is low. Therefore, we hypothesized that adapting the AF2-M protocol is necessary to enrich for specific conformations, thereby enabling the prediction of both pre- and postfusion conformations. AF2-M requires only the input sequence and internally generates multiple sequence alignments (MSAs) and optional templates before applying its pretrained model weights. We tested the use of template data to enrich pre- or postfusion conformations and demonstrated that our approach significantly increases the prediction frequency of class I fusion protein structures in both conformations, with the template dataset playing a crucial role in guiding modeling towards the intended state. Furthermore, we showed that the lack of correlation between pLDDT and TM-scores suggests that low pLDDT values may obscure the presence of valid alternative conformations.by Jing-le Zhuge, Xi-yong Li, Yong-le Wang, Juan-fen Ma
ObjectiveThis study aimed to comprehensively analyze differentially expressed genes (DEGs) in chondrocytes from patients with knee osteoarthritis (OA) by integrating multiple machine learning algorithms and bioinformatics techniques, to unravel the underlying molecular mechanisms associated with OA chondrocytes, and to provide novel insights for the innovation of clinical therapeutic strategies.
MethodsWe downloaded the GSE117999, GSE114007, GSE169077, GSE246425, and GSE178557 datasets from the public Gene Expression Omnibus (GEO) database as the training set, while GSE57218 served as an independent validation set. To ensure data consistency and comparability, the training set was normalized, and the ComBat algorithm was applied to eliminate batch effects, yielding a merged gene expression dataset. Subsequent differential expression analysis was performed to identify genes with significant changes under disease conditions, followed by enrichment analysis. To more accurately identify genes closely linked to disease characteristics, we independently analyzed the merged dataset using three machine learning algorithms: Lasso regression, random forest, and support vector machine (SVM). The intersection of results from these three methods was used to construct a robust list of disease-related feature genes. These prominent feature genes were validated in the training set and further externally confirmed using the GSE57218 dataset. Additionally, the CIBERSORT algorithm was employed to quantify immune cell infiltration in the normalized gene expression data, selecting infiltration results with high reliability (P Results
DDIT3 and PFKFB3 were significantly downregulated in OA patients. DDIT3 was specifically associated with lipid metabolism, apoptosis, and inflammatory genes (e.g., TNFRSF12A), whereas PFKFB3 was linked to phospholipid synthesis and cell cycle genes (e.g., CHKA). Both genes were associated with core OA-related pathways, including PI3K-Akt and AGE-RAGE. Immune infiltration analysis revealed that DDIT3 was positively correlated with pro-inflammatory mast cells and M1 macrophages, while PFKFB3 was negatively correlated with activated dendritic cells. Collectively, these two genes were associated with immune cell infiltration patterns. The competing endogenous RNA (ceRNA) network analysis indicated that DDIT3 was associated with axes such as LINC00689-miR-769-5p, and PFKFB3 was associated with complex networks like GAS6-AS1-miR-146a-5p.
ConclusionDDIT3 and PFKFB3 are key candidate genes associated with the pathological progression of OA. Their downregulation is correlated with inflammatory and metabolic disturbances in chondrocytes, supporting their potential use as diagnostic biomarkers and therapeutic targets for OA.
by Ying Fei, Ming-Yi Gao, Nan Qiao, Jia Hu, Ling He, Jiao-Li Zhou, Ning-Ning Zheng, Ting-Ting Liu
BackgroundThe effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.
MethodsTranscriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.
ResultsTen key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.
ConclusionAn association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.
by Sara Grafenauer, Belinda Durey, Kevin Norton
Barbie and Ken dolls have been criticized over time for their overt misalignment of body shape in comparison with the average adult, and the possibility that this impacts the formative minds of children, particularly girls. Updating a previous examination of the original Barbie and Ken dolls from 1996, this study compared the body measures of the 2016 “Fashionista” range—including Curvy, Petite, Tall, and Standard Barbie models, and new Malibu Ken—with representative population data of young adult females and males using anthropometric techniques. A range of anthropometric girth measures plus height were taken from each doll, and body proportions were calculated. The rules of allometry were used to scale the dolls to a standardized adult height of 170.18 cm to determine the dimensions the dolls at this adjusted size. The dimensions were then compared to the same height-adjusted reference population norms used in the original study. The comparison revealed significant alterations in the dolls’ morphology compared with the original Barbie and Ken, with key measures of waist-to-hip and chest-to-waist ratios becoming more realistic and falling within the 95% confidence range of the population. According to z-score deviation data, Curvy Barbie fell closest to the mean for most of the scaled girth measures, while new Ken was closer to the mean for all girths except ankle. Design changes reflect a shift toward greater body diversity, with potential benefits for children’s health behaviours through the production of a broader range of more diverse, human-like dolls. Importantly, key measurements and body proportions were generally closer to the respective reference populations.by Su-jin Kim, Jinhee Kim
BackgroundPost-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.
ObjectivesIn this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.
MethodsWe conducted an online survey of 629 adults in Korea who experienced persistent symptoms ≥12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2®. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.
ResultsA four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes (p Conclusions
Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.
by Gunnhild Helmsdal, Marnar Fríðheim Kristiansen, Eyðbjørg Klemmentsen Gaard, Barbara Joensen Eysturoy, Pál Weihe, Eina Hansen Eliasen, Maria Skaalum Petersen
BackgroundSix years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.
ObjectivesThe aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.
MethodsWe conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).
ResultsA total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13–1.30, p Conclusions
One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.
by Natsuhiro Takahashi, Akihiko Fujita, Yuki Azetsu, Akiko Karakawa, Mie Myers, Masamichi Takami, Masahiro Chatani
Bone loss occurs in astronauts during prolonged spaceflight, thus indicating the sensitivity of skeletal homeostasis to altered gravitational environments. Previous studies have shown that microgravity affects osteoclast differentiation and bone resorption, which suggests that osteoclasts possess mechanisms to sense and respond to gravity-generated mechanical forces. For testing of the related mechanisms, hypergravity can be experimentally reproduced with use of a centrifuge. In the present study, osteoclasts derived from mouse bone marrow were subjected to hypergravity under three conditions: 30G exposure using a non-CO2 centrifuge system, and short- or long-term exposure to 3G or 5G using an incubator-compatible centrifuge system. Cytoskeletal organization and resorptive function were assessed using TRAP (tartrate-resistant acid phosphatase) staining, F-actin visualization, and dentin pit assays. In addition, phosphoproteomic analysis was performed after short-term exposure to 5G hypergravity. Hypergravity exposure for as brief as 30 minutes compromised F-actin ring integrity, reduced fluorescence intensity, and promoted nuclear repositioning toward actin rings, whereas tubulin and vinculin localization remained unchanged, and the structural alterations corresponded to attenuated resorption pit formation. Quantitative phosphoproteomic profiling revealed coordinated hypergravity-dependent changes in phosphorylation across multiple cellular modules, including cytoskeletal organization, membrane trafficking, intracellular signaling, and nuclear regulatory pathways. Together, these results indicate that osteoclasts are sensitive to gravity-generated mechanical loading, with hypergravity rapidly modifying F-actin-associated cytoskeleton properties and reprogramming phosphorylation-dependent signaling networks, ultimately attenuating bone-resorptive activity. These findings provide mechanistic insight into how osteoclasts respond to altered gravitational loading conditions and have implications for skeletal adaptation during spaceflight and under altered mechanical loading conditions on Earth.by Burç İhsan Gencel, Melahat Çelik Güven, Uğur Mercan, Süleyman Çağatay Dayan, Onur Geçkili
BackgroundMandibular two-implant overdentures are considered the standard of care for edentulous patients. The attachment system and the shape of the bone crest can significantly influence biomechanical behaviours. This study aimed to evaluate stress distribution in mandibular implant-supported overdentures using locator and bar attachments across various bone crest designs.
Materials and methodsFEA was performed on mandibular overdentures supported by two implants. Three crest configurations (flat, convex, and irregular) were modelled with either bar or locator attachments. A vertical force of 100 N was applied in three loading conditions: anterior, unilateral molar, and bilateral molar. Maximum von Mises stresses and principal stresses were assessed.
ResultsAnterior loading resulted in the highest stresses across all groups, with peak values reaching 12 N/mm² in the convex and irregular models. Bilateral molar loading consistently produced the lowest and most uniform stress distributions, while unilateral loading caused intermediate stress concentrations on the working side. Uneven platforms significantly increased stress levels, particularly under unilateral bar loading. Locator attachments showed slightly reduced stresses after bilateral loading in irregular crest configurations. Stress concentrations were primarily localized at the implant neck and prosthetic connectors.
ConclusionStress distribution in mandibular overdentures is significantly influenced by loading direction, crest shape, and attachment mechanism. Anterior loading poses the highest biomechanical risk, while bilateral posterior loading provides optimal conditions. Vertical discrepancies in implant platforms heighten stress concentrations, underscoring the importance of careful surgical planning. Locator attachments offer limited biomechanical advantages in uneven crest scenarios, supporting their use in anatomically challenging cases.
by Imteaz Mahbub, Bimal Chandra Shil, Sadeed Araf Reza
BackgroundFunctional dyspepsia (FD) is a common gastrointestinal disorder with multifactorial pathogenesis. Recent evidence suggests that duodenal eosinophilia may contribute to low-grade immune activation in FD. This study evaluated the association between increased duodenal eosinophil count and functional dyspepsia.
Materials and methodsThis case-control study was conducted in the Department of Gastroenterology, Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh, from January to December 2022. Forty-six adult patients with functional dyspepsia diagnosed by Rome-III criteria were included as cases, while forty age- and sex-matched individuals without functional dyspepsia undergoing upper gastrointestinal endoscopy for other indications with normal endoscopic findings served as controls. Multiple biopsies were obtained from the second part of the duodenum. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin and eosin. Eosinophils were counted manually by light microscopy in five randomly selected high- power fields (x 400 magnification), and the mean eosinophil count per high-power field (HPF) was calculated.
ResultsThe mean duodenal eosinophil count was significantly higher in patients with functional dyspepsia compared with controls (23.98 ± 7.98 versus 15.63 ± 5.94 eosinophils/HPF, p Conclusions
Patients with functional dyspepsia demonstrated significantly greater duodenal eosinophil infiltration than controls, supporting the role of low-grade immune activation in its pathogenesis. Further multicenter studies with larger samples are required to clarify the clinical implications of duodenal eosinophilia in functional dyspepsia.
by Tatsuya Yoshihara, So Owada, Harumasa Arita, Akiko Nakagomi, Kota Tanaka, Yosuke Ono, Osamu Yoshino
BackgroundTo investigate the association between menstrual-related disorders and sexually transmitted infections (STI) among young women in Japan, and to examine differences according to disorder type and hormonal therapy use.
MethodsThis cross-sectional study used the Japan Medical Data Center Claims Database and included women younger than 40 years who had at least one healthcare visit in 2023. Menstrual-related disorders were defined as endometriosis or dysmenorrhea based on ICD-10 codes. The prevalence of five STIs—gonorrhea, genital chlamydia infection, trichomoniasis, genital herpes, and other sexually transmitted conditions—was compared between women with and without menstrual-related disorders. Subgroup analyses were conducted for endometriosis, dysmenorrhea, and hormonal therapy (low-dose estrogen–progestin combinations or dienogest). Prevalence ratios (PR) and prevalence differences (PD) with 95% confidence intervals (CI) were estimated.
ResultsAmong 3,440,929 women, 257,897 (7.5%) had menstrual-related disorders. All STI were substantially more prevalent in this group than in women without menstrual-related disorders, with PRs ranging from 4.31 to 5.29. Endometriosis showed the highest prevalence, particularly for genital chlamydia infection (4.98%; PR 7.44). Dysmenorrhea was also associated with consistently elevated STI prevalence. Among women with menstrual-related disorders, STI prevalence differed only slightly according to hormonal therapy use, with differences generally within one percentage point.
ConclusionMenstrual-related disorders were strongly associated with increased diagnosis of STI in Japanese young women. These findings highlight the importance of integrating STI screening and reproductive health education into routine gynecologic care for women with endometriosis or dysmenorrhea. The influence of healthcare-seeking behavior and diagnostic patterns should be considered when interpreting claims-based STI data.
by Sneha Vidyasagar, Kanakamani Jeyaraman, Syeda Farah Zahir, Paul Varghese
ObjectiveThis retrospective study evaluated calcitonin as an adjunct therapy for reducing phantom limb pain (PLP) following lower limb amputation.
MethodThe study included 35 patients who received at least 3 days of calcitonin treatment between January 1, 2017, and December 31, 2023. We collected demographic data and pain ratings (intensity, distress, and interference with activity) before and after calcitonin treatment. Descriptive statistics and paired t-tests analysed the data, with a two-way repeated measures ANOVA used to compare outcomes between patients with and without diabetes. Raw and Standardized mean differences (Cohen’s d) are presented for each measure.
ResultsThe average age of participants was 57.09 years (SD = 13.66), with 40% female. Amputation types were below-knee (65.7%), above-knee (25.7%), and other (8.6%). The main causes of amputation included diabetic foot infection (25.7%), peripheral vascular disease (34.3%), trauma (25.7%), and other (14.3%). Ten participants had diabetes, and 20% had depression.Calcitonin was associated with significant reductions in pain outcomes from pre- to post-intervention (Day 0 to Day 7), with calcitonin given from day 1–3. Mean pain intensity decreased from 6.41 to 5.24 (Cohen’s d = 0.66); p = 0.02), and pain-related distress decreased from 5.85 to 4.81 (Cohen’s d = 0.71; p = 0.014). Perceived pain relief scores increased from 33.69 to 58.21, indicating greater patient-reported pain relief following treatment (Cohen’s d = 0.53; p = 0.035). No significant differences in pain intensity or distress were observed between patients with and without diabetes. Additionally, there was no significant change in the Oral Morphine Equivalent Daily Dose (p = 0.94).
ConclusionIn conclusion, calcitonin significantly reduced perceived pain intensity and pain-related distress scores while increasing perceived pain relief scores (i.e., patients’ reported degree of pain reduction), with similar effects observed in both patients with and without diabetes.
by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger
Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing IRX3 expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting IRX3 enhances hiPSC-CM differentiation. IRX3-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, IRX3-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that IRX3 expression peaks during the early stages of cardiomyocyte differentiation, whereas IRX3-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and TBX5, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.by Wen Lin, Qiong-zhi Shi, Xiang-ru Liao, Yuan Zeng, Xiang-yang Xie, Gang-jian Ji, Yin-ke Li
Burn wound infections are frequently complicated by biofilm-forming and multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), posing major therapeutic challenges. Antimicrobial peptides (AMPs) such as PL-5 (peceleganan) exhibit broad-spectrum activity but are limited by instability, poor biofilm penetration, and reduced efficacy in complex wound environments. Here, a red-light-responsive, porphyrin-phospholipid (PoP)-containing cationic liposomal system for PL-5, aiming to enhance its antibacterial and antibiofilm performance was developed. Optimized liposomes achieved high encapsulation efficiency (~73%), uniform nanoscale size (~50 nm), narrow polydispersity, and positive surface charge. They demonstrated good storage stability and controlled peptide release under red-light irradiation (635 nm). In vitro, red-light activation significantly enhanced antimicrobial activity against MRSA and methicillin-susceptible S. aureus (MSSA), reducing minimum inhibitory concentration (MIC) values fourfold and accelerating bactericidal kinetics compared with free PL-5 and non-irradiated liposomes. Additionally, red-light-activated liposomes markedly inhibited biofilm formation. These results indicate that light-responsive liposomal delivery enables spatiotemporally controlled release of PL-5, significantly potentiating its antibacterial and antibiofilm efficacy. This approach offers a promising localized treatment strategy for biofilm-associated burn wound infections and a foundation for future translational studies.
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