Search PubMedSearch

SEARCH · Search PubMed

Results for “Hydroxyl (OH) radicals”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

45 records · Page 2Linked to original sources

Effects of erector spinae plane block on postoperative pain in patients undergoing implant-based breast reconstruction for breast cancer: a randomized controlled trial.

BACKGROUND: Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE: To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN: Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING: Tertiary cancer center in China. PATIENTS: 100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION: Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 &#x3bc;g/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES: Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS: ESPB did not significantly reduce resting pain at 6 h at the median (&#x3c4; =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (&#x3c4; = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS: Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06143020.

Humans

Strategies for mosaic variant calling in brain disorders.

The human brain is a genomic mosaic, where postzygotic mutations arising from embryogenesis to senescence drive diverse neurodevelopmental and neurodegenerative diseases. Because of numerous sequencing artifacts at ultralow variant allele frequencies (VAFs), detecting these variants remains a significant analytical challenge. This review focuses on single-nucleotide variants and small indels, summarizing current strategies for aligning sampling methods, including bulk, laser capture microdissection, and single-cell genomics, with the expected clonal architecture of the brain. It emphasizes that mosaic detection sensitivity is fundamentally constrained by sequencing depth, since even the most advanced algorithms cannot identify variants not physically represented in the sequencing library. The review further recommends the selection of variant calling algorithms based on validated VAF detection performance, matching tools like MuTect2 and MosaicForecast to their optimal performance ranges. Furthermore, we discuss how multitissue sampling, as emphasized by the SMaHT project, addresses the matched-control dilemma and supports accurate variant classification via cross-tissue VAF gradients. Integrating these established pipelines with multiomics modalities, including transcriptomic and epigenetic data, could advance the field toward a functional understanding of how the somatic genome impacts human brain health and disease.

Humans

Protein persulfidation emerges as a conserved component of the redox response to DNA damage.

Genotoxic stress is frequently accompanied by alterations in cellular redox homeostasis; however, the mechanisms linking redox regulation to the DNA damage response (DDR) remain incompletely understood. Here, we investigated the early redox response to DNA damage induced by methyl methanesulfonate (MMS) in Saccharomyces cerevisiae, focusing on cysteine oxidative post-translational modifications (PTM). We show that activation of the DNA damage response is accompanied by rapid redox changes that occur in the absence of a generalized oxidative stress response. MMS exposure promotes selective remodeling of cysteine oxidative modifications, characterized by decreased free thiols, robust induction of protein persulfidation, and comparatively modest changes in sulfenylation. These alterations are accompanied by increased intracellular hydrogen sulfide levels, supporting the involvement of reactive sulfur species in the cellular response to DNA damage. Proteome-wide analyses revealed that cysteine oxidative modifications preferentially target proteins involved in central metabolism, nucleotide biosynthesis, and genome maintenance. Consistent with these observations, MMS-induced genotoxic stress promotes metabolic adaptation characterized by increased mitochondrial respiration, elevated ATP production, and mitochondrial morphological remodeling, linking bioenergetic adaptation to redox regulation. Importantly, perturbation of intracellular redox balance using N-acetylcysteine compromises survival under DNA-damaging conditions, supporting a functional role for redox signaling during the DDR. Finally, MMS treatment also induces protein persulfidation in mammalian cells. Moreover, exposure to etoposide, a mechanistically distinct genotoxic agent that induces DNA double-strand breaks through topoisomerase II inhibition, showed a similar trend, suggesting that protein persulfidation may not be restricted to alkylation-induced DNA damage. Together our findings identify protein persulfidation as a prominent component of the redox response to DNA damage and provide new insight into the functional interplay between mitochondrial metabolism, cysteine-based redox regulation, and genome maintenance.

Oxidation-Reduction

Genomic characterization and pathogenicity of ruminant Listeria monocytogenes isolates in a murine oral infection model.

Listeria monocytogenes is a major foodborne pathogen; its ruminant isolates display zoonotic characteristics, causing similar clinical signs in humans, including abortion and encephalitis. However, data on whole genome sequencing and pathogenicity of ruminant L. monocytogenes isolates remain sparse. This study aimed to analyze the genotypic characteristics of L. monocytogenes isolates from ruminants with listeriosis. Furthermore, we assessed the in vivo pathogenicity of four ruminant L. monocytogenes isolates, characterized via whole-genome sequencing-based genetic clustering, in orogastrically inoculated mice. The isolate LM18 (serotype 1/2b, ST224, SL6178) had the lowest lethal dose compared to the other three isolates including previous hypervirulence type (serotype 4b, ST1, SL1) and caused secondary bacteremia in lungs, with sustained bacterial loads in the spleen and liver. Genomic (listeria pathogenicity island -1 and -3) and virulence gene (actA and llsX) mutation analyses associated with virulence suggested from well-recognized studies could not elucidate the virulence of the isolates. SSI-1, which only exists in the isolate LM18 (serotype 1/2b, ST224, SL6178), may help L. monocytogenes survive in the gastrointestinal environment, thereby affecting its virulence. Further research should investigate the role of SSI-1 in the pathogenicity of L. monocytogenes. Moreover, additional studies utilizing larger datasets of ruminant isolates are required to validate our genotypic characterization and to obtain a comprehensive picture of further genotypic differences crucial for L. monocytogenes pathogenicity.

Animals

EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation.

SMARCA4-deficient thoracic malignancies comprise biologically heterogeneous tumors, ranging from conventional non-small cell lung cancer with SMARCA4 alterations to thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), an aggressive entity frequently associated with concomitant SMARCA2 loss. However, the extent to which SMARCA4-deficient lung cancer cell lines recapitulate SMARCA4-UT-like biology remains incompletely defined. Here, we characterized lung cancer cell lines across distinct SMARCA4 and SMARCA2 states and identified a subgroup with SMARCA4/2 co-deficiency that exhibited reduced expression of epithelial lineage markers and transcriptional similarity to SMARCA4-UT and other SWI/SNF-deficient malignancies. The EZH1/2 inhibitor HM97662 selectively suppressed growth in SMARCA4/2-deficient cells, with limited effects in SMARCA2-proficient cells. EZH1/2 inhibition broadly reduced H3K27me3 and induced derepression of PRC2 targets regardless of drug sensitivity. However, its biological effects were most pronounced in SMARCA4/2-deficient cells, where it promoted apoptosis, reduced stemness marker expression, attenuated the SMARCA4-UT-associated transcriptional signature, and suppressed proliferative and mTORC1-related programs. Chromatin accessibility analysis further revealed cell-line-specific patterns of accessibility loss, with reduced accessibility at stemness-associated transcription factor motif-enriched regions coupled with transcriptional repression of nearby genes in SMARCA4/2-deficient cells. These findings support dual EZH1/2 inhibition as a potential therapeutic vulnerability in SMARCA4/2-deficient, SMARCA4-UT-like lung cancer cells.

Humans

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30&#xa0;kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50&#xa0;kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P&#x202f;<&#x202f;0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

Humans

CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study.

OBJECTIVE: Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS: Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS: From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and &#x3b2;-NGF (p < 0.05) and PGE2, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION: This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

Humans

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27&#x202f;&#xb1;&#x202f;7&#x202f;y) and 24 older adults (12M/12F, age 67&#x202f;&#xb1;&#x202f;8&#x202f;y) were randomized to receive either placebo or PB125 (200&#x202f;mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8&#x202f;&#xb1;&#x202f;1.5 to 3.8&#x202f;&#xb1;&#x202f;1.3%, p&#x202f;<&#x202f;0.0001) and popliteal FMD (PB125: 1.5&#x202f;&#xb1;&#x202f;1.5 to 2.3&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.033) in older, but not younger adults (both, p&#x202f;>&#x202f;0.27). During bed rest, PB125 preserved brachial (3.8&#x202f;&#xb1;&#x202f;1.3 to 3.6&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.543) and popliteal FMD (2.3&#x202f;&#xb1;&#x202f;1.4 to 2.7&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.269), LVC (1.1&#x202f;&#xb1;&#x202f;0.8 to 1.1&#x202f;&#xb1;&#x202f;1.5 AUC, p&#x202f;=&#x202f;0.530) and circulating SOD concentrations (28.3&#x202f;&#xb1;&#x202f;7.2 to 28.6&#x202f;&#xb1;&#x202f;8.6 U/mL, p&#x202f;=&#x202f;0.888) in older adults compared to placebo (all, p&#x202f;<&#x202f;0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4&#x202f;&#xb1;&#x202f;2.8 to 3.4&#x202f;&#xb1;&#x202f;1.8%, p&#x202f;=&#x202f;0.302) in younger adults compared to placebo (p&#x202f;<&#x202f;0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae

Home-Based Cardiac Rehabilitation Using a Smart Ring and Telephone Counselling: A Randomized Controlled Trial.

BACKGROUND: Home-based cardiac rehabilitation (HB-CR) is a promising alternative to center-based cardiac rehabilitation as it can address several barriers impeding CR implementation because of its enhanced accessibility. However, to date, HB-CR has not garnered adequate attention due to a lack of communication between patients and medical staff. In this study, we aimed to investigate the effectiveness of HB-CR by monitoring the pulse rate (PR) using a smart ring equipped with photoplethysmography. METHODS: Patients with cardiovascular disease were educated on structured HB-CR methods following a symptom-limited cardiopulmonary exercise test (CPET), and were instructed to wear the device during the exercise session. The recorded PR was uploaded to a website via a smartphone and monitored by medical staff. Patients were randomly assigned to one of two groups: intervention or control group. The intervention group received weekly telephone counselling and was encouraged to maintain optimal levels of physical activity. In contrast, the control group only recorded their exercise data without additional interventions. After 3 months of training, the CPET was performed. RESULTS: Among the 64 randomized patients (32 in each group), an intention-to-treat analysis showed that peak oxygen consumption increased over time in both the groups, with a significantly greater improvement in the intervention group. The group-by-time interaction for peak oxygen consumption was statistically significant (estimated mean difference, 2.0 mL/kg/min; 95% confidence interval, 0.7-3.3; P = 0.004). CONCLUSION: HB-CR using a smart device was effective in improving oxygen consumption. However, appropriate monitoring and timely counselling by medical professionals are important for improved outcomes. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005893.

Humans

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, &#x3b2;-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. &#xa9; 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit

Posterior Segment Risk Factors for Penetrating Keratoplasty Failure.

PURPOSE: To analyze the relationship between intraoperative and postpenetrating keratoplasty (PK) posterior segment variables and PK graft survival. DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients undergoing PK between May 1, 2007 and September 1, 2018 at a single tertiary center. METHODS: Chart review for PKs performed was conducted, and the first PK completed at the institution for each patient was included for analysis. Data collected included demographics, medical and ocular history, preoperative and intraoperative findings, and intraoperative and postoperative posterior segment factors (pars plana vitrectomy [PPV], endolaser, retinal detachment [RD], and vitreous hemorrhage [VH]). After univariable analysis, variables were selected for multivariable Cox regression analysis. MAIN OUTCOME MEASURE: Graft failure, defined as irreversible and visually significant corneal edema, haze, or scarring. RESULTS: Eight hundred and thirty-five eyes of 835 patients were included. Mean age was 57.1 &#xb1; 22.0 (range: 0-100) years, and mean time from PK to final follow-up or graft failure was 3.2 &#xb1; 2.9 (range: 0.01-16.1) years. Graft failure occurred in 35.0% of cases with a mean onset of 1.9 &#xb1; 2.0 (range: 0.04-11.4) years after PK. After multivariable analysis, 9 variables had significant associations with failure. Two posterior segment variables were significant: intraoperative VH at the time of PK (hazard ratio [HR] 6.6, 95% confidence interval [CI] 1.6-27.7, P = .010) and silicone oil (SO) tamponade after the PK (HR 3.2, 95% CI 1.4-7.4, P = .007). CONCLUSIONS: Graft failure is a serious complication of PK. VH at the time of the PK and SO tamponade after the PK were associated with graft failure. In complex eyes that are undergoing PK grafts and that may also require posterior segment interventions, these findings may guide patient counseling and discussion of graft prognosis.

Humans

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, &#x3b1;-smooth muscle actin (&#x3b1;SMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors

Effectiveness of Mobile-Delivered Exercise and Yoga Programs on Depressive Symptom Reduction in Employees: Randomized Controlled Trial.

BACKGROUND: Mental health challenges such as stress and depression are prevalent among employees. Mobile health platforms that deliver exercise or yoga interventions offer a promising approach to improve mental health outcomes in this population. OBJECTIVE: This study aimed to assess the effectiveness of 12-session adaptive moderate-intensity exercise and yoga programs delivered via a motion-detecting digital platform in reducing stress and depressive symptoms among employees. METHODS: This was an unblinded, 3-arm, parallel-group, randomized controlled trial conducted at Seoul National University Bundang Hospital and Boramae Medical Center between November 2023 and January 2024. Eligible participants were full-time employees. Seventy-five participants were randomly assigned to an exercise, a yoga, or a cognitive behavioral therapy-based self-care control group using computer-generated randomization. The exercise and yoga groups engaged in motion-detecting, adaptive physical activity training, whereas the control group accessed mobile-based, self-directed stress management educational materials. The intervention was largely automated, with no individualized therapeutic guidance provided. Allocation was concealed until trial entry. All recruitment and outcome assessments were conducted in person at the hospitals. The primary outcomes were perceived stress and depressive symptoms, whereas the secondary outcomes included posttraumatic stress, insomnia severity, cognitive stress response, occupational stress, and burnout. Physiological outcomes were assessed using heart rate variability and electroencephalography. Measurements were collected at baseline, immediately after the intervention, and at 4-week follow-up. Data were analyzed using a multivariate linear model to evaluate the main effects of time, group, and time&#xd7;group interactions. RESULTS: Of the 75 randomized participants (exercise: n=24, 32%; yoga: n=25, 33.3%; and control: n=26, 34.7%), 71 (94.7%) who completed at least 9 of the 12 sessions (&#x2265;40 min each) were included in the outcome analysis (exercise: n=21, 29.5%; yoga: n=24, 33.8%; and control: n=26, 36.6%). For the coprimary outcomes, the group&#xd7;time interaction for depressive symptoms (Patient Health Questionnaire-9) approached but did not reach the Bonferroni-corrected threshold (F4,136=2.71; P=.03; adjusted &#x3b1;=.025); however, planned pairwise comparisons revealed significantly greater improvement in the yoga group compared to the control group at 4-week follow-up (&#x3b2;=-3.67; adjusted P<.001). For the Perceived Stress Scale, the interaction was not significant (P=.29), although a significant main effect of time (P<.001) indicated overall stress reduction across all groups. For secondary outcomes, a significant group&#xd7;time interaction was found for the Cognitive Stress Responses Scale (P=.003), indicating differential trajectories of improvement. The yoga group showed a consistent linear decrease, whereas the exercise group showed immediate but less sustained gains. CONCLUSIONS: Digitally delivered adaptive yoga programs demonstrated superior and sustained improvements in depressive symptoms and Cognitive Stress Responses Scale scores compared with the active cognitive behavioral therapy-based self-care control group. However, the exercise program showed more modest and less sustained effects, warranting further investigation using larger samples.

Adult

Minimally invasive versus open surgery for gallbladder cancer: A systematic review and meta-analysis.

INTRODUCTION: Minimally invasive surgery (MIS) is increasingly being used in gallbladder cancer (GBC) for radical tumour extirpation. However, there are conflicting results on the morbidity outcomes following MIS. The aim of this meta-analysis was to compare the post-operative morbidity and mortality in patients undergoing radical surgery for GBC between MIS and open surgery. MATERIAL AND METHODS: Studies comparing MIS (laparoscopic, robotic or both techniques) to open surgery were included. The databases of MEDLINE, Cochrane and EMBASE were searched from 2001 till March 2025. The primary end point was post-operative morbidity and mortality. The secondary end points were hospital stay, blood loss, operative time and R1 resection rates. Random effect models were used for analysis. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Thirty-two studies (laparoscopic [n&#x202f;=&#x202f;19], robotic [n&#x202f;=&#x202f;6] or both [n&#x202f;=&#x202f;7]) involving 8568 (MIS&#x202f;=&#x202f;3287 and open&#x202f;=&#x202f;5281) patients were included. For overall and major morbidity (Clavian-Dindo >/&#x202f;=&#x202f;III), the odds ratio (OR) of 0.60 (95% CI: 0.46-0.78) and 0.72 (95% CI: 0.52-1.0) respectively was obtained, favouring the MIS approach. Similarly, MIS showed lower odds for mortality [OR:0.62 (95% CI: 0.40-0.95)] compared to open surgery. MIS was associated with shorter hospital stay (less by mean of 3 days) and lesser blood loss (less by mean of 115&#x202f;ml) but longer operative time (higher by mean of 5.8&#x202f;min) and higher R1 resection rates (OR: 1.34; 95% CI: 1.05-1.71). Oncological outcomes, however, were comparable. The certainty of evidence was very low to low across the studies. CONCLUSION: MIS for GBC was associated with relatively lower post operative morbidity and mortality with similar oncological outcomes but with a small but heightened risk of margin positive (R1) resection, especially in primary GBC. The certainty of evidence was very low to low across the included studies. Future prospective studies are needed to overcome the clinical heterogeneity and possible selection bias.

Humans

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (&#x3b7;&#xa0;=&#xa0;42.08%), raising the tumor temperature above 45&#xa0;&#xb0;C within 90&#xa0;s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of &#xb7;OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals