Albuminuria is one of the most important biomarkers of chronic kidney disease and also a target that can be influenced by treatment. The amount of albumin excreted in the urine is an independent predictor of declining kidney function, cardiovascular events, and all-cause mortality. It is most easily determined based on the albumin-to-creatinine ratio (ACR) measured in the first morning urine sample; in the vast majority of cases, 24-hour urine collection is not required. The pathophysiology of albuminuria centers on damage to the glomerular filtration barrier - particularly podocytes - hemodynamic hyperfiltration, inflammation associated with tubular protein reabsorption, and activation of the renin-angiotensin-aldosterone system (RAAS). Modern four-pillar pharmacotherapy - RAS inhibitors (ACE inhibitors/ARBs), SGLT2 inhibitors, non-steroidal mineralocorticoid receptor antagonists (finerenone), and GLP1 receptor agonists in type 2 diabetes - acts on these processes through complementary mechanisms. When tailored to the degree of albuminuria and eGFR, this treatment significantly slows the progression of chronic kidney disease and reduces cardiovascular risk. Measuring and monitoring albuminuria must therefore be an essential part of daily clinical practice. Orv Hetil. 2026; 167(31): 1231-1237. Az albuminuria a krónikus vesebetegség egyik legfontosabb biomarkere és egyben terápiásan befolyásolható célpont. A vizelettel ürülő albumin mennyisége a vesefunkció-romlás, a cardiovascularis események és az összmortalitás önálló prediktora. Meghatározása a legegyszerűbben a reggeli első vizeletmintából meghatározott albumin/kreatinin hányados (ACR) alapján történik; az esetek túlnyomó hányadában nincs szükség 24 órás vizeletgyűjtésre. Az albuminuria patofiziológiájának középpontjában a glomerularis filtrációs barrier – különösen a podocyták – sérülése, a hemodinamikai hiperfiltráció, a tubularis fehérjereabszorpcióhoz kapcsolódó gyulladás és a renin-angiotenzin-aldoszteron rendszer (RAAS) aktivációja áll. A modern négypilléres farmakoterápia – RAS-gátló (ACE-gátló/ARB), SGLT2-gátló, nemszteroid mineralokortikoidreceptor-antagonista (finerenon) és 2-es típusú diabetesben GLP1-receptor-agonista – egymást kiegészítő mechanizmusokon keresztül hat ezekre a folyamatokra. A kezelés az albuminuria mértékéhez és az eGFR-értékhez igazítva érdemben lassítja a krónikus vesebetegség progresszióját, és csökkenti a cardiovascularis rizikót. Az albuminuria mérése és monitorozása ezért a mindennapi klinikai (egyben háziorvosi) gyakorlat elengedhetetlen része kell, hogy legyen. Orv Hetil. 2026; 167(31): 1231–1237.
U-wave changes during angina are often not recognized, although a change in U-wave polarity may be the only sign of myocardial ischemia. The appearance of a positive U-wave in leads V1-4 during angina suggests posterobasal ischemia and critical stenosis of the CX or RCA coronary artery. The authors present two examples. Orv Hetil. 2026; 167(31): 1248-1252. Az angina alatti U-hullám-változásokat gyakran nem ismerik fel, pedig az U-hullám polaritásváltozása lehet akár az egyedüli jele a myocardialis ischaemiának. A V1–4-elvezetésekben a pozitív U-hullám angina alatti megjelenése posterobasalis ischaemiára és CX vagy RCA coronariabetegség kritikus szűkületére utal. A szerzők erre mutatnak két példát. Orv Hetil. 2026; 167(31): 1248–1252.
In addition to other conditions involving increased muscle spasms, centrally acting muscle relaxants (guaifenesin, tolperisone, methocarbamol, chlorzoxazone, diazepam, baclofen and tizanidin) provide relief for a significant proportion of patients suffering from low back pain. Of these, tolperisone has recently been restricted by official decision due to the high incidence of anaphylactic reactions associated with its use. The aim of our work is to analyze the frequency of side effects of this group of drugs in order to help clinicians choose the appropriate medication. According to data from the World Health Organization, tolperisone is considered a safe drug, except for the aforementioned serious allergic side effect. Mortality (including suicide) associated with the administration of these medicines is the highest among the reported side effects for diazepam, followed by tizanidine and methocarbamol. Ineffectiveness was most commonly reported for guaifenesin, followed by baclofen and tizanidine. Tolperisone was the most favorable drug in terms of both mortality and ineffectiveness. We present in detail the gastrointestinal, major neurological, and psychiatric side effects that make it difficult, and in some cases impossible, to take the drugs, and we also mention the disturbing skin and eye symptoms. Orv Hetil. 2026; 167(31): 1224-1230. Az egyéb, fokozott izomspasmussal járó kórképek mellett a derékfájdalomban szenvedő betegek jelentős részének enyhülést hoznak a centrálisan ható izomrelaxánsok (guaifenezin, tolperizon, metokarbamol, klórzoxazon, diazepám, baklofen és tizanidin). Ezek közül az utóbbi időben a tolperizon hatósági döntés következtében visszaszorult, mivel alkalmazása során nagy arányban tapasztaltak anafilaxiás reakciókat. Közleményünk célja a fenti gyógyszercsoport mellékhatásai gyakoriságának elemzése, hogy ennek bemutatásával segítsük a klinikusokat a megfelelő gyógyszerválasztásban. Az Egészségügyi Világszervezet adatai szerint az említett súlyos allergiás mellékhatást leszámítva a tolperizon biztonságos szernek számít. A gyógyszerhez kapcsolható halálozás (az öngyilkosságot is beleértve) a jelentett mellékhatások között a diazepám esetében a legnagyobb arányú, amit a tizanidin és a metokarbamol követ. Hatástalanságról a leggyakrabban a guaifenezin esetében számoltak be, ezt a baklofen és a tizanidin követi. A halálozás és a hatástalanság tekintetében is a tolperizon volt a legkedvezőbb szer. Részletesen bemutatjuk a szerek szedését megnehezítő, egyes esetekben ellehetetlenítő gastrointestinalis, major neurológiai és pszichiátriai mellékhatásait, valamint megemlítjük a zavaró bőr- és szemészeti tüneteket is. Orv Hetil. 2026; 167(31): 1224–1230.
Over recent decades, non-pharmacological pain management approaches have gained increasing importance in pediatric care, as they can be applied with low cost and minimal time investment while significantly contributing to the improvement of care quality. The aim of this review article is to provide an overview of non-pharmacological options for procedural pain management based on the literature, and to present the dissemination of this approach in Hungary through the support of a child-centered, trust-based healthcare model. This paper presents a narrative review of the key findings of international literature on non-pharmacological management of procedural pain. In addition, it describes the practical implementation of an interdisciplinary non-pharmacological pain management program based on the principles of the Comfort Promise, which has been operating since 2021 at the Bethesda Children's Hospital of the Hungarian Reformed Church. The article outlines the steps of implementation, the tools and techniques applied, and summarizes clinical experiences. Methods shown to be effective in the literature - such as distraction, breathing exercises, comfort positioning, breastfeeding, and the use of various sensory tools - are, in line with international evidence, also supported by clinical experience as contributing to the reduction of children's anxiety, increasing parental satisfaction, and improving the quality of care. Experience suggests that integrating non-pharmacological methods into everyday clinical practice does not require significant additional resources; however, it does necessitate a shift in mindset and a structured implementation process. Interdisciplinary collaboration, staff training, the establishment of a volunteer network, and the active involvement of parents and children are key factors for sustainable implementation. Based on current experience, the combined application of this approach and its methods has proven to be effective. According to international literature, anxiety-reducing interventions - including parental presence, appropriate information provision, distraction, and relaxation techniques - contribute to the alleviation of procedural pain through neural mechanisms influencing pain perception, which is also supported by the institutional experience presented. Orv Hetil. 2026; 167(31): 1215-1223. Az elmúlt évtizedekben a nem gyógyszeres fájdalomcsillapító eljárások egyre nagyobb szerepet kapnak a gyermekellátásban, mivel kis költséggel és csekély időráfordítással alkalmazhatók, ugyanakkor jelentős mértékben hozzájárulhatnak az ellátás minőségének javításához. A jelen összefoglaló közlemény célja a procedurális fájdalomkezelés nem gyógyszeres lehetőségeinek áttekintése a szakirodalom mentén, valamint a szemlélet hazai elterjedésének bemutatása egy gyermekközpontú, bizalomra épülő egészségügyi ellátási modell támogatásával. A közlemény narratív áttekintés formájában ismerteti a procedurális fájdalom nem gyógyszeres kezelésére vonatkozó nemzetközi szakirodalom főbb megállapításait, továbbá ismerteti a Magyarországi Református Egyház Bethesda Gyermekkórházában 2021 óta működő, a Comfort Promise alapelveire épülő interdiszciplináris nem gyógyszeres fájdalomkezelési gyakorlat megvalósítását. Bemutatja a bevezetés lépéseit, az alkalmazott eszközöket és technikákat, valamint összefoglalja a klinikai tapasztalatokat. A szakirodalomban hatékonynak bizonyuló eljárások – így a figyelemelterelés, a légzőgyakorlatok, a kényelmes pozicionálás, a szoptatás, valamint a különböző szenzoros eszközök alkalmazása – a nemzetközi evidenciákkal összhangban a klinikai tapasztalatok alapján is hozzájárulnak a gyermekek szorongásának csökkentéséhez, a szülői elégedettség növeléséhez és az ellátás minőségének javításához. Tapasztalatok alapján a nem gyógyszeres módszerek integrálása a mindennapi klinikai gyakorlatba nem igényel jelentős többleterőforrást, ugyanakkor szemléletváltást és strukturált bevezetést tesz szükségessé. Az interdiszciplináris együttműködés, a személyzet képzése, az önkéntes hálózat kiépítése, valamint a szülők és gyermekek aktív bevonása kulcsfontosságú az implementáció és a fenntarthatósága szempontjából. Az eddigi tapasztalatok alapján a szemléletmód és a módszerek kombinált alkalmazása eredményes megközelítésnek bizonyult. A nemzetközi szakirodalom alapján a szorongáscsökkentést célzó módszerek – beleértve a szülői jelenlétet, a megfelelő tájékoztatást, a figyelemelterelést és a relaxációs technikákat – a fájdalomélményt befolyásoló neuralis mechanizmusokon keresztül hozzájárulnak a procedurális fájdalom mérsékléséhez, amit a bemutatott intézményi gyakorlat tapasztalatai is megerősítenek. Orv Hetil. 2026; 167(31): 1215–1223.
According to epidemiological data from Hungary, cardiovascular diseases cause the greatest loss of health among the population and are responsible for a significant proportion of premature deaths. This reinforces the health policy position that cardiovascular prevention, including improving medication adherence, must be given top priority in patient care. Long-term survival in patients who have experienced acute coronary syndrome depends heavily on medication adherence, particularly regarding statins and anticoagulants; however, domestic surveys indicate deficiencies in the use of preventive medications. The aim of our study was to compare the attitudes and beliefs regarding antiplatelet agents and cholesterol-lowering drugs among patients in the secondary prevention group who underwent percutaneous coronary intervention and those in the primary prevention control group, using the Beliefs about Medicines Questionnaire (BMQ). A cross-sectional, questionnaire-based study included 162 secondary prevention patients and 136 primary prevention patients who had undergone percutaneous coronary intervention. Medication attitudes were measured using the specific and general dimensions of the BMQ, and SPSS 27.0 was used for statistical analysis. Among patients in the secondary prevention group, both drug groups were characterized by lower levels of concern and more accepting attitudes, whereas in the primary prevention group, sceptical (p<0.05) and ambivalent attitudes were more common (p<0.001). Based on the analysis of respondents by attitude group and the examination of the BMQ's general subscales, percutaneous coronary intervention significantly influenced beliefs regarding medications. This change was clinically significant in terms of treatment adherence (p<0.001) Discussion and conclusion: Patients who have undergone percutaneous coronary intervention have more favourable attitudes toward medication, which highlights the role of targeted education and psychoeducation in improving adherence in the non-intervention population. However, adherence in the secondary prevention group cannot be considered optimal either, therefore further targeted education is warranted in this patient group as well. Orv Hetil. 2026; 167(31): 1238-1247. Bevezetés: Magyarországi epidemiológiai adatok alapján a cardiovascularis betegségek okozzák a legnagyobb egészségveszteséget a lakosság körében, és az idő előtti halálozás jelentős részéért is felelősek. Ez megerősíti azt az egészségpolitikai álláspontot, hogy a cardiovascularis prevenciónak, beleértve a gyógyszeres terápiahűség javítását, kiemelt prioritást kell kapnia a betegellátásban. Az akut coronaria szindrómán átesett betegek hosszú távú túlélése nagymértékben függ a gyógyszeres terápiahűségtől, különösen a sztatinok és véralvadásgátlók tekintetében, ugyanakkor hazai felmérések a preventív gyógyszerek szedésének hiányosságaira utalnak. Célkitűzés: Vizsgálatunk célja a percutan coronariaintervención átesett másodlagos prevenciós és a kontrollcsoportba tartozó elsődleges prevenciós betegek thrombocytaaggregáció-gátlókkal és koleszterinszint-csökkentőkkel kapcsolatos hozzáállásának és hiedelmeinek összehasonlítása volt a Beliefs about Medicines Questionnaire (BMQ) segítségével. Módszerek: Keresztmetszeti, kérdőíves vizsgálatban 162 percutan coronariaintervención átesett másodlagos prevenciós és 136 elsődleges prevenciós beteg vett részt. A gyógyszerattitűdök mérése a BMQ speciális és általános dimenziói mentén történt, a statisztikai elemzéshez az SPSS 27.0 programcsomagot alkalmaztunk. Eredmények: A másodlagos prevenciós betegek esetében elmondható, hogy mindkét gyógyszercsoport esetében kisebb aggodalomszint és elfogadóbb hozzáállás volt jellemző, míg az elsődleges prevenciós csoportban gyakoribb volt a szkeptikus (p<0,05) és az ambivalens hozzáállás (p<0,001). A válaszadók attitűdcsoportok szerinti elemzése, valamint a BMQ általános alskáláinak vizsgálata alapján a percutan coronariaintervencióhoz társulóan szignifikáns különbségek voltak megfigyelhetők a gyógyszerekkel kapcsolatos hiedelmeket illetően. Ez a változás a gyógyszeres terápiahűséggel összefüggő attitűdök szempontjából jelentős volt (p<0,001). Megbeszélés és következtetés: A percutan coronariaintervención átesett betegek kedvezőbb gyógyszerattitűdökkel rendelkeznek, ami kiemeli a célzott edukáció és pszichoedukáció szerepét a nem intervención átesett populáció terápiahűségének javításában. Ugyanakkor a terápiahűség a másodlagos prevenciós csoportban sem tekinthető optimálisnak, ezért ebben a csoportban is indokolt a további célzott betegoktatás alkalmazása. Orv Hetil. 2026; 167(31): 1238–1247.
Some subtypes of avian influenza A viruses (IAVs) have been associated with human infections (e.g. H3N8, H5Ny, H7Ny, H9N2, and H10Ny), and the ability of these viruses to cause zoonotic infections further increases the public health risk of avian IAVs. Among them, H9N2 virus is one of particular importance, both in its own right and as a contributor of internal gene segments to other emerging zoonotic avian IAVs. In recent years, an increasing number of H9N2 strains have been observed to be highly pathogenic in mice without prior adaptation. In this study, we found that a naturally occurring H9N2 isolate, A/chicken/Jiangxi/198/2019 (JX198), is lethal in mice. To investigate the molecular basis for the high virulence of JX198 in mice, a series of reassortants and mutants were generated and tested. We found that the PA, especially D347G mutation in PA, is responsible for the increased pathogenicity of JX198 in mice. Notably, D347G in PA of JX198 significantly alters the polymerase activity, vRNA production, and plaque-formation. Thus, our data demonstrate that a novel molecular marker, D347G in PA, determines the virulence of H9N2 in mice, posing a potential risk of H9N2 with D347G in PA for public health and highlighting the significance of continuing surveillance of H9N2 field strains.
Microbial consortia offer significant advantages over monocultures in biotechnological applications, including access to a broader metabolic repertoire, functional redundancy and the capacity for division of labour. Adaptive laboratory evolution (ALE) has similarly proven to be a powerful tool in metabolic engineering, uncovering solutions inaccessible through rational design alone. Despite their individual potential, the intersection of ALE and synthetic microbial consortia in bioproduction contexts remains underexplored. This review examines recent advances at this intersection, with a focus on bottom-up synthetic consortia and co-cultures. Artificial selection operates at organismal and supra-organismal levels in microbial communities, and this not only shapes their productive output, but it may also compromise the evolvability of costly production functions. This effect can be limited by engineering ecological interactions that stabilise community composition. ALE and synthetic consortia mutually expand each other's applicability through a variety of implementation logics. However, current approaches predominantly rely on growth-based selection, and we argue that implementing inter-community artificial selection strategies holds considerable untapped potential.
Selective lipophagy requires cargo recognition and recruitment of autophagy receptors to lipid droplets (LDs), yet the molecular mechanisms that couple LDs to the core autophagy machinery remain poorly defined. Here, we identified the small GTPase RAB18 (RAB18, member RAS oncogene family) as an upstream initiator of lipophagy that directly recruited the macroautophagy/autophagy receptor OPTN (optineurin) to LDs in osteoblasts. Lipid stress induced RAB18 activation and its localization to LDs, where RAB18 engaged OPTN enabling OPTN-LC3 bridging and lysosomal degradation of LDs. Loss of either RAB18 or OPTN impaired lipophagic flux, resulting in lipid accumulation and defective osteogenic differentiation, whereas OPTN overexpression partially rescued RAB18 deficiency, supporting a hierarchical RAB18-OPTN pathway. Thus, while OPTN acted as a critical effector downstream of RAB18, it did not feed back to promote RAB18 recruitment. In vivo, perturbation of this axis compromised bone regeneration under hyperlipidemic conditions. Together, these findings establish RAB18-dependent recruitment of OPTN as a molecular mechanism for selective lipophagy and reveal lipophagy as a critical metabolic adaptation that sustains osteoblast function during lipid stress.Abbreviations: AAV: adeno-associated virus; ALP: alkaline phosphatase; Baf A1: bafilomycin A1; CC domain 1: coiled-coil domain 1; CCK-8: cell counting Kit-8 kit; Co-IP: co-immunoprecipitation; ER: endoplasmic reticulum; HE: hematoxylin and eosin; IF: immunofluorescence; IHC: immunohistochemistry; KD: knockdown; LDs: lipid droplets; Micro-CT: microscopic computerized tomography; OE: overexpression; OPTN: optineurin; qRT-PCR: quantitative real-time polymerase chain reaction; RAB18: RAB18, member RAS oncogene family; ROI: region of interest; SD: standard deviations; TBK1: TANK binding kinase 1; TEM: transmission electron microscopy; WB: western blot.
Persistent and semi-volatile organic contaminants remain important atmospheric tracers because of their environmental persistence, multiple emission pathways and capacity for regional transport. This study investigated the spatial and seasonal variability of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in northeastern France. Nitrogen-doped carbon-coated silicon carbide foam (NMC@SiC) passive air samplers were deployed at six urban, suburban and rural sites in the Strasbourg metropolitan area between 2018 and 2020. Twenty-one OCPs, sixteen PAHs, and twenty-two PCBs were quantified by gas chromatography-tandem mass spectrometry. PAHs exhibited the clearest spatial and seasonal variability, with higher concentrations at urban sites and cold-season or autumn enhancements depending on the location. Naphthalene dominated the PAH profile, while diagnostic ratios suggested dominant combustion inputs, including traffic, residential heating and biomass or solid-fuel burning. PCBs showed weaker spatial contrasts and more homogeneous distributions, with profiles dominated by penta-, hexa- and hepta-chlorinated congeners, indicating diffuse legacy contamination, possible PCB-containing materials, industrially influenced areas and regional redistribution. OCPs were dominated by dichlorodiphenyltrichloroethane-related compounds and hexachlorocyclohexane isomers, reflecting historical residues and secondary volatilization from contaminated environmental reservoirs. These findings highlight the combined influence of current urban emissions, persistent legacy reservoirs, secondary re-emissions and regional atmospheric transport on organic contaminant distributions in northeastern France.
Accelerator mass spectrometry (AMS) is one of the most precise analytical tools for tracing fossil fuel-derived CO2 in the atmosphere. In this study, deciduous tree leaves were collected from Gyeongju and neighboring cities in South Korea to analyze the radiocarbon (Δ14C) characteristics of atmospheric CO2. The measured Δ14C values were used to estimate fossil fuel-derived CO2 concentrations (CO2_ff, ppm) for comparison among the different regions. The sampling locations were expanded incrementally from 2018 to 2024, with 12 sampling sites in 2024. A comparison of Δ14C and CO2_ff revealed clear spatial differences associated with regional characteristics, such as traffic density, population activity, and industrial emissions. Long-term observations from 2018 to 2024 indicated persistent Δ14C depletion in densely populated and industrialized areas, highlighting the sensitivity of radiocarbon to changes in human activity levels. Industrial areas exhibited substantially lower Δ14C values and correspondingly higher (≤23.6 ppm) CO2_ff concentrations than rural areas. These results demonstrate that regional fossil fuel-derived CO2 distributions are influenced by regional differences in human activity.
ALKBH5, as an m6A demethylase, plays a crucial regulatory role in various kidney diseases such as acute kidney injury, chronic kidney disease, renal fibrosis and renal cell carcinoma. However, its function often exhibits contradictory effects: In renal fibrosis, ALKBH5 has been reported to both promote and suppress fibrogenesis, whereas in renal cell carcinoma most studies support an oncogenic role, but some clinical observations link ALKBH5 downregulation to poor prognosis. These contradictions may stem from differences in cell types, disease stages, and microenvironments. This manuscript systematically reviews the complex function of ALKBH5 in kidney diseases and its underlying mechanisms, explores its potential as a therapeutic target, evaluates its therapeutic potential, and highlights the need for cell- and pathology-specific strategies to enable precise intervention. Future research should focus on its cell and pathological background specificity to achieve precise intervention.
To facilitate personal identification for mass disaster victims, we aimed to develop and evaluate a deep learning method for matching postmortem computed tomography (PMCT)-derived RaySum images with antemortem chest X-rays (CXRs). This retrospective study included PMCT images and antemortem CXRs of 1385 deceased individuals. RaySum images were generated from archived PMCT data after extracting the body trunk segment between the seventh cervical and third lumbar vertebrae. An EfficientNet-B3 model with AdaCos metric learning was pretrained on ChestX-ray14 of NIH and applied without task-specific fine-tuning. Each RaySum image was used as a query to the CXR galleries with three timing categories: the "oldest-date examination", the "nearest-date examination", and "all examinations". The galleries also included 78,999 non-matching CXRs. Performance was evaluated based on our top-k correct identification rates, and the "oldest" and "nearest-date" categories were compared using the exact McNemar test. The "all examinations" category achieved identification rates of 83.0% at top-1, 90.6% at top-5, 93.2% at top-10, and 95.2% at top-20. The "nearest-date" examination significantly outperformed the "oldest-date" examination in all evaluated thresholds, including top-1 rates of 78.9% versus 54.2% (p < 0.001). The "all examinations" category showed numerically higher performance than the "nearest-date" category, although the "all examinations" included a larger and variable number of true-match images. PMCT-derived RaySum images are considered to provide high retrieval performance in a one-to-many CXR gallery. This approach may help narrow down candidates from image galleries and prioritize potential matches, assisting the following detail forensic examinations.
This study investigated the structural and functional modifications of chickpea albumin (CPA) through conjugation with hydrolyzed guar gum (GG) via the Maillard reaction. CPA-GG conjugates were prepared at different protein-to-polysaccharide ratios (1:1, 1:3, and 3:1) and characterized in terms of solubility, ζ-potential, surface hydrophobicity, secondary structure, and molecular properties. Conjugation-induced structural rearrangements include a reduction in α-helix content (from 35% to 7-9%) and an increase in β-sheet content (from 21% to 45-48%). Conjugation increased the molecular weight of CPA from 137 kDa to 425-708 kDa and rendered the conjugates more conformationally rigid. All conjugates exhibited enhanced emulsifying activity compared with native CPA (0.02 m2/g), with the polysaccharide-rich conjugate (C13) showing the highest value (31.62 m2/g) at pH 6.5 and improved emulsion stability at pH 3.5. This study demonstrates that Maillard conjugation effectively improved the techno-functional properties of CPA.
Dynamic benzyl-hydrazone crosslinks are widely used in covalent adaptable hydrogels due to their hydrolytic stability and tunable exchange kinetics. This reversibility enables competitive inhibition strategies in which small-molecule competitors modulate network dynamics by replacing crosslinking sites. Here, we demonstrate that adding molecules to compete with crosslinks can unintentionally perturb hydrogel mechanics through environmental effects, including changes in pH and ion concentration, in addition to direct bond disruption. In benzyl-hydrazone hydrogels, methyl hydrazine competitors unexpectedly increased the average relaxation time rather than accelerating network exchange. To decouple environmental effects from competitive inhibition, we systematically investigate how pH, ion concentration, and buffer composition influence hydrogel mechanics. We find that increasing ion concentration enhances the storage modulus, consistent with salt-mediated stabilization. Comparison across biologically relevant media further reveals that relaxation dynamics vary significantly with buffer identity, even when elastic moduli remain similar. Notably, more basic environments lead to markedly slower network relaxation, even in the presence of competitors to the crosslink. These findings demonstrate that, in competitively inhibited benzyl-hydrazone hydrogels, pH, ion concentration, and buffer identity can influence network mechanics in ways that differ from the expected effects of competitor addition alone, highlighting the need for careful interpretation of competitive inhibition experiments.
Tyrosine kinase inhibitors are recommended as maintenance therapy following allogeneic stem cell transplantation (HSCT) for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), but optimal medication, dose, and duration remain a subject of ongoing study. We provide the final analysis of a prospective randomized trial comparing prophylactic and minimal residual disease (MRD)-triggered imatinib maintenance. The two patient cohorts did not differ significantly in terms of cumulative incidence of relapse (CIR; 14% vs. 18%), non-relapse mortality (NRM; 12% vs. 11%), leukemia-free survival (LFS) 64% vs. 69%, and overall survival (OS) at 10 years (68% vs. 71%). Endpoints were assessed every 6 weeks within the trial from 4 weeks after SCT until EOS at week 55 and after that according to local standards. In summary, this provides a framework for MRD-based treatment of patients for maintenance after HSCT with excellent long-term outcome after 10 years in both groups.
Chalkbrood, a destructive larval disease caused by the fungal pathogen Ascosphaera apis, causes substantial losses in apiculture. Although host-pathogen interactions in Apis mellifera larvae infected with A. apis have been investigated, immune defense mechanisms in the Asian honey bee Apis cerana remain unclear. This study examined whether the lncRNA6470/ace-miR-750-y axis modulates the response of A. cerana larvae to A. apis infection. Stem-loop RT-PCR, Sanger sequencing, dual-luciferase reporter assays, RNA interference, and RT-qPCR were used to characterize ace-miR-750-y, lncRNA6470, AcPP2A, host immune genes, and selected A. apis genes associated with signal transduction, transcriptional regulation, and RNA metabolism. Larval survival and chalkbrood incidence were also evaluated after ncRNA perturbation. ace-miR-750-y was expressed in larval guts and showed infection-associated expression changes. Computational prediction identified 214 candidate mRNA targets and 143 candidate lncRNA interactors of ace-miR-750-y, from which the lncRNA6470/ace-miR-750-y/AcPP2A axis was selected for experimental validation. Modulation of ace-miR-750-y significantly affected AcPP2A expression. ace-miR-750-y overexpression increased host immune genes associated with antimicrobial peptide production and peroxidase activity, whereas its inhibition reduced their expression. Modulation of ace-miR-750-y was also associated with altered expression of selected A. apis genes and changes in larval survival and chalkbrood incidence. These findings suggest that ace-miR-750-y may play an important regulatory role in the immune response of A. cerana worker larvae to A. apis infection, and that its interaction with lncRNA6470 may contribute to ceRNA-like regulation during fungal challenge.
Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are at increased risk of sepsis, yet the comparative infection-related outcomes of newer antihyperglycemic agents remain unclear. We evaluated the associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter 2 inhibitors (SGLT2is) with infection outcomes in this population. In this retrospective cohort study using the TriNetX global federated database, individuals aged 40-100 years with coexisting COPD and T2DM who initiated a GLP-1RA or SGLT2i between 2021 and 2024 were identified. A new-user, active-comparator design with 1:1 propensity score matching was applied. Sepsis was the primary outcome; all-cause mortality and components of the primary outcome were secondary. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). After matching, 45,491 pairs were included. Compared with SGLT2is, GLP-1RAs showed lower risks of sepsis (adjusted HR, 0.832; 95% CI, 0.781-0.887), all-cause mortality (0.642; 0.598-0.689), and severe sepsis (0.841; 0.774-0.914). In patients with COPD and T2DM, GLP-1RAs were associated with significantly lower risks of sepsis and all-cause mortality compared with SGLT2is.
Post-ovulatory aging (POA) reduces oocyte quality, yet effective interventions remain limited. Here we demonstrate that early intervention with vitamin K2 (menaquinone-4 isoform, MK-4) alleviates POA by inhibiting iron-disorder-induced oxidative stress. Western blot revealed that the expressions of ferroptosis suppressor protein 1 (FSP1) and vitamin K epoxide reductase-like protein (VKORC1L1) were significantly decreased in mouse POA oocytes; however, MK-4 attenuated these changes. Further, MK-4 inhibited ferritinophagy by downregulating NCOA4 and LC3II, markedly restored ferritin level, reduced intracellular Fe2+ amount, thus attenuating oxidative stress. These results were characterized by reducing lipid peroxidation marker malondialdehyde (MDA) and acyl-CoA synthetase long chain family member 4 (ACSL4) expression, decreasing γ-H2AX and 8-Hydroxy-2'-deoxyguanosine (8-OHdG), and enhancing expression of the mitochondrial antioxidant enzyme superoxide dismutase 1 (SOD1). Additionally, MK-4 suppressed mitophagy by downregulating PINK1 and Parkin, and upregulating Rab7 improving mitochondrial membrane potential. Consequently, abnormalities in chromosomes, spindles, and the cytoskeleton were significantly ameliorated in POA oocytes receiving early MK-4 intervention. Notably, in vitro-aging oocytes expressed higher FSP1 and VKORC1L1 but lower ACSL4 and MDA versus the in vivo counterparts, suggesting a milder lipid peroxidation in vitro. Collectively, our findings uncover a novel anti-aging mechanism triggered by MK-4, highlighting its potential to establish a preventive strategy for female reproductive aging.
People with substance use disorders (PWSUDs) frequently experience multifaceted challenges, including depression, stigma, and social instability, which can negatively affect their quality of life (QoL). The present study explored the potential predictors of QoL among PWSUDs. The sample consisted of 300 PWSUDs (85% males; mean [SD] age = 44.73 [10.01] years), comprising equal groups of PWSUDs with amphetamine, opioid, and alcohol concerns. Variables such as education, employment, depression, self-esteem, and stigma were assessed. The Taiwan version of the World Health Organization Quality of Life (WHOQOL) Questionnaire was adapted to assess QoL. Hierarchical regression analyses were conducted to examine associations with QoL across four domains. A multiple mediator modeling approach was used to assess whether self-stigma and depression mediated the relationship between perceived stigma and QoL. Higher depression scores were consistently associated with lower QoL across all domains. Education and employment were positively associated with physical QoL. In the psychological domain, both lower depression and higher self-stigma were associated with higher QoL. Perceived stigma was negatively associated with social QoL, and lower education predicted poorer environmental QoL. Mediation analyses suggested that depression played a stronger mediating role than self-stigma in the association between perceived stigma and QoL. Depression and stigma significantly related to QoL among PWSUDs. Mediational pathways suggest that targeting depression may mediate the negative association between stigma and QoL. Interventions addressing both affective and social dimensions may help promote recovery.