Self-assembled monolayers (SAMs) are key interfacial modifiers for inverted perovskite solar cells (IPSCs), yet their design is often constrained by a trade-off between suppressing molecular aggregation and maintaining efficient charge transport. Here we introduce a π-extended nonplanar molecular design to decouple interfacial morphology control from electronic coupling. Two tetracene-fused SAM molecules, tetraceno-fused carbazole phosphonic acid (PATCz) and tetraceno-fused dibenzazepine phosphonic acid (PATDBAz), were synthesized via dehydrocyclization. While PATCz forms a helicene-like twisted structure, PATDBAz adopts a butterfly-shaped nonplanar geometry that enables Butterfly-shaped π-extended "wings" to form effective intermolecular π-π stacking while preventing excessive aggregation. This structural feature promotes ordered interfacial assembly, improved energy-level alignment, and efficient hole transport. Consequently, PATDBAz-based IPSCs achieve a champion power conversion efficiency of 26.47% and retain 97.5% of their initial efficiency after 1000 h under International Summit on Organic Photovoltaic Stability light-soaking level 1 (ISOS-L-1) conditions. This work highlights π-extended nonplanar frameworks as an effective strategy for designing high-performance SAMs in perovskite photovoltaics.
Prolonged infusion (extended [EI, 2-4 h] or continuous [CI, 24 h] extended) of beta-lactam antibiotics is considered to have advantages for patients with severe infection compared with intermittent bolus (IB). However, the choice of EI and CI is unclear due to the lack of direct comparison. We aimed to compare the EI and CI of beta-lactams in patients with severe infections using a network meta-analysis method. We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, and Weipu Database for randomized controlled trials (RCTs) comparing EI, CI, or IB with beta-lactams in adults with severe infections. The primary outcome was all-cause mortality. A frequentist network meta-analysis with a random-effects model was performed. Risk of bias was assessed using the Cochrane RoB 2 tool. Thirty-five RCTs (10,627 patients) were included. Risk of bias was moderate to high in most studies. For mortality, EI ranked highest (SUCRA 74.20%) with numerically lower rates versus IB (EI: OR 0.80, 95% CI 0.55-1.17; CI: OR 0.86, 95% CI 0.62-1.02). Both EI and CI significantly improved clinical cure rates versus IB (EI: OR 1.58, 95% CI 1.13-2.23; CI: OR 1.35, 95% CI 1.05-1.85), and EI ranked first (SUCRA 87.72%). For microbiological success, CI ranked highest (SUCRA 83.03%), followed by EI (SUCRA 42.98%) and IB (SUCRA 23.99%), but no significant difference was found. For hospital stay, EI was associated with a reduction of borderline statistical significance (MD -3.49 days, 95% CI -6.79 - -0.08), whereas CI did not show a significant reduction (MD 1.11 days, 95% CI -1.24 - 3.63), and EI ranked best (SUCRA 98.09%). No significant adverse event differences were observed. Subgroup analyses showed variable treatment rankings across categories, with no statistically significant subgroup effects. In patients with severe infections, both EI and CI improved clinical cure versus IB, whereas mortality did not differ significantly. Indirect evidence suggests EI may be more effective than CI in most outcomes except microbiological response. EI trended to shorten hospital stay but the difference was of borderline significance. Considering its practical feasibility, EI appears to be a favorable option based on current evidence. However, this finding is based on indirect evidence and requires confirmation in head-to-head trials. PROSPERO CRD420251242437.
Immersive extended reality (iXR) technologies are increasingly adopted within health professions education. However, existing evidence has largely focused on technical skill acquisition or learner satisfaction, with limited examination of how iXR supports the development of clinical reasoning (CR) as a cognitive process. A scoping review was conducted using the Arksey and O'Malley framework and reported in accordance with PRISMA ScR guidance. Searches were undertaken across MEDLINE, CINAHL, Scopus, and Embase. Studies were included if they examined iXR interventions and reported outcomes related to CR across health profession disciplines at Kirkpatrick Level 2 or above. Studies limited to reaction-level outcomes were excluded. Data were charted and synthesised to identify iXR modalities, targeted components of CR, evaluative approaches, and impact. Twenty-four studies published between 2018 and 2026 were included, most involving nursing students. Eleven studies used self-reported measures of CR or related constructs (level 2a), while thirteen used observed or performance-based approaches (level 2b). Of the 2b studies, most inferred reasoning from task performance, structured outputs, or construct-aligned tools, while only two explicitly elicited learners' reasoning processes. No studies examined sustained behavioural change or transfer of CR to practice. Across the full dataset, sixteen studies reported findings supportive of iXR for CR-related outcomes or for making learners' reasoning processes more visible, seven reported no significant difference over comparator approaches and one reported negative findings. All studies reporting neutral or negative findings included comparator instructional approaches, whereas only a minority of studies reporting supportive findings included comparators. Current evidence does not demonstrate sustained or transferable improvements in CR using iXR. However, interpretation is constrained by inconsistent construct definitions and reliance on short-term, self-reported, or task-specific outcome measures. iXR may be more useful for eliciting and evaluating learners' reasoning processes within simulation, than for demonstrating durable improvement in CR.
Dupilumab is effective for moderate-to-severe atopic dermatitis, but optimal long-term dosing is unclear. In this single-centre retrospective study, 49 patients underwent dose extension to 300 mg Q3W or 300 mg Q4W, with EASI scores remaining low and stable over 18 months. Patients extending for good disease control had higher EASI90 rates. The impact of age, disease severity and therapy duration remains uncertain.
Lower-extremity peripheral artery disease often requires endovascular therapy. Target-lesion restenosis (TLRS) remains frequent, but current risk stratification is limited. We retrospectively analyzed 1,005 lesions from 917 patients undergoing endovascular therapy for lower-extremity atherosclerotic disease at a single center (2019-2024) with scheduled surveillance (approximately 6, 12, and 24 months) and administrative censoring at 36 months. The primary endpoint was time to first TLRS ≥ 50%, adjudicated by duplex ultrasound (peak systolic velocity ratio criteria) or CTA/DSA when available. Lesion‑level Fine-Gray competing‑risk models (death as a competing event) with patient‑level clustering were used. A prespecified Core model (clinical, anatomic, procedural/device covariates and C‑reactive protein) was compared with an Extended model additionally including the Atherogenic Index of Plasma (AIP) and log‑transformed Systemic Immune-Inflammation Index (SII). Models were internally validated by 1,000 bootstrap resamples and assessed at the 24‑month horizon using the C‑index, calibration, Brier score, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision‑curve analysis. Among 917 patients (1,005 lesions), mean age was 75.2 ± 11.7 years and 68.6% were male. At 24 months, cumulative incidences were 31.4% for TLRS, 14.9% for clinically driven target‑lesion revascularization, and 12.3% for death. In multivariable analyses, GLASS stage III, lesion length ≥ 150 mm, residual stenosis > 20%, chronic kidney disease, and Rutherford class 4-6 predicted higher TLRS risk, whereas good distal runoff was protective. In the Extended model, AIP and SII remained independent predictors and improved the optimism‑corrected 24‑month C‑index from 0.68 to 0.73 (Δ0.05, p = 0.002), reduced the Brier score (0.19 to 0.17), yielded positive IDI and NRI, and preserved good calibration. Exploratory analyses suggested lower TLRS risk with cilostazol and low‑dose rivaroxaban plus aspirin. AIP and SII improved lesion-level prediction of TLRS beyond conventional covariates. The Extended model may support risk-tiered surveillance after endovascular therapy; external validation is warranted.
Herein, we present a new class of hybrid conjugated polymer that integrates [8]cycloparaphenylene ([8]CPP) directly into poly(para-phenylene vinylene) (PPV) frameworks, creating a π-extended poly(cyclo(para-phenylene vinylene)) ([8]CPPV). Comprehensive characterization confirmed its well-defined alternating structure. Photophysical analyses revealed curvature-driven electronic coupling between the radial CPP and linear PPV π-systems, resulting in broadened absorption, red-shifted emission, and high fluorescence quantum yield. Furthermore, [8]CPPV demonstrates excellent performance as a lithium-ion battery anode, combining high initial capacity with stable cycling enabled by mixed pseudocapacitive and diffusion-controlled Li+ storage mechanisms. These results establish [8]CPPV as a versatile all-carbon polymeric framework that bridges molecular nanohoops and extended π-networks, offering a tunable platform for optoelectronic and energy storage applications.
The evolution of mite sensitization profiles from childhood to adulthood is associated with distinct clinical outcomes. Longitudinal sensitization trajectories have never been addressed across two generations over an extended time frame. Using molecular diagnosis, we aimed to investigate how the evolution of mite sensitization relates to the expression of rhinitis and asthma in adult versus pediatric patients over a 20-year period. Specific IgE (sIgE) to mite molecular allergens was determined using the MeDALL allergen chip (Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 37, 18, 21 and 23; Der f 1, Der f 2, Lep d 2, Blot t 5). Assessment was made in adult (n = 21), adolescent (n = 11), and pediatric patients (n = 19) with rhinitis and/or asthma, in T1 (20-years ago) and in T2 (current time). After the 20-year period, the adult cohort significantly decreased the number of sIgE responses to mite components-T1: 7 [3-9] versus T2: 4 [2-6], median [IQR], p = .0040. A strong negative correlation was observed between age and the 20-year variation of sensitization count (r = -0.5305; p < .0001). In adults, the reduction in mite molecular IgE responses was associated with improvement in rhinitis (p = .0010) and asthma (p = .0020), reflecting disease progression patterns not observed in the pediatric cohort. This is the first analysis to show that molecular mite sensitization declines with aging, and this reduction may relate to decreased asthma and rhinitis symptoms and severity. This age-associated decline highlights the importance of careful clinical interpretation in older adults to avoid overtreatment and missed diagnoses.
By reducing the duration of the vitrification-warming procedure to 1 min does ultra-rapid vitrification-warming (URV/W) effectively maintain oocyte viability and improve clinical outcomes compared to conventional vitrification-warming (CV/W) timing (14 min) and what is the effect of the two procedures on cellular stress? URV/W shortens procedure time, reduces cryoprotectant exposure, improves oocyte survival, and is associated with fewer transcriptomic alterations in oocytes than CV/W. CV/W techniques require extended cryoprotectant exposure and micromanipulation, which elevate cellular stress and the risk of cryoinjury. URV/W procedures address these challenges by reducing exposure and manipulation, though comparative data on clinical outcomes and transcriptomic signatures in human oocytes remain limited. The study was performed between August 2024 and December 2024 and included a clinical cohort and a transcriptomic cohort to provide a thorough assessment of the effects of cryopreservation methodology on oocyte and embryo viability, development, and cellular stress. The clinical cohort comprised 1077 oocytes used to evaluate clinical outcomes following CV/W and URV/W. The study also included a prospective analysis involving 68 oocytes from 4 donors in the transcriptomic cohort. Oocytes and trophectoderm biopsy samples from blastocyst-stage embryos were assigned to three groups: fresh, CV/W, and URV/W. The clinical study was performed using a total of 1077 oocytes from 46 donors, which were matched and allocated for the comparison of clinical outcomes between CV/W (n = 519) and URV/W (n = 558). Following vitrification-warming, the oocytes were fertilized via ICSI for assessment of embryo development and clinical outcomes. In the transcriptomic cohort of the study, transcriptomic testing and analysis were performed as part of the prospective analysis to compare CV/W and URV/W in terms of their effectiveness in oocyte freezing and warming, their impact on embryo development, and their effects at the molecular level. A total of 68 samples were obtained from 4 donors, including eight oocytes and eight trophectoderm biopsy samples from each of the three groups. These samples were analyzed to investigate the cellular effects of cryopreservation-induced stress through transcriptomic profiling. The single-cell transcriptomic study included preparation of cDNA libraries followed by next-generation sequencing to investigate differential gene expression across oocytes and embryonic trophectoderm cells in the three groups. This method allowed for the comprehensive monitoring of transcriptional activity, enabling the detection and quantification of mRNA molecules to evaluate the transcriptomic signatures of the study groups. In addition, functional enrichment analyses of up- and downregulated genes were conducted and classified based on gene ontology to identify potential pathways associated with embryo quality and cellular stress. Transcriptomic analysis indicated that gene expression patterns following URV/W were more similar to fresh oocytes than those undergoing CV/W. Differences in gene expression patterns among blastocysts from the three groups were minimal, as the total number of differentially expressed genes was limited. Oocytes subjected to URV/W demonstrated a significantly higher survival rate, lower post-ICSI degeneration, and produced more high-quality Day-5 blastocysts compared to those vitrified using CV/W methods (P < 0.001 for all comparisons). These findings are unlikely to be solely attributable to differences in procedural timing, as fertilization, cleavage, euploidy, clinical pregnancy, and live birth rates were comparable between groups (P > 0.05 for all comparisons). All oocyte samples donated (1145) for research purposes were included in the study without quality-based selection. Only embryos reaching the blastocyst stage on Days 5 or 6 using the URV/W method were included in the transcriptomic analysis. Embryos not reaching these stages were excluded. Consequently, only data from embryos with optimal development and good quality were analyzed, and compared among the three groups. Obtaining cDNA in single-cell studies is a novel and challenging process, particularly due to the limited availability of RNA. While advanced clinical evaluations can still be conducted on biopsied oocytes and embryos, the failure to obtain cDNA from the same samples may result in incomplete data, which can limit the overall scope and outcomes of the study. The comprehensive single-cell transcriptomic data obtained from this expanded dataset will help delineate pathways altered by different vitrification methods, providing critical insights into their efficacy and potential risks in clinical practice. Additionally, the findings will illuminate key genes and pathways involved in embryonic stress, enabling the development of more cost-effective, targeted gene panels for evaluating these factors. This study was funded by the Sanatórium pre liečbu neplodnosti SPLN's, Ovogene and Mikrogen Genetic Diagnosis Laboratory's own resources. A.V.P. is a Medical Science Liaison for Kitazato Corporation-Dibimed. His role in the study was strictly scientific and unrelated to any commercial interest. All the other co-authors declare no conflicts of interest. n/a.
Neonatal intensive care units (NICUs) concentrate ethically complex decision-making, yet the leadership behaviours supporting nurses' ethical agency remain insufficiently understood, particularly outside Western contexts. To explore how moral leadership is experienced and enacted in shaping ethical decision-making among NICU nurses. Qualitative narrative inquiry, reported in accordance with COREQ and SRQR. Twenty-four registered nurses were recruited through purposive maximum-variation sampling across four Level III NICUs in northern Saudi Arabia. Narrative interviews (52-97 min; mean ≈ 74 min) were conducted over an eight-month period, from June 2025 to January 2026, and analysed using a narrative analysis approach integrating thematic and structural elements. Trustworthiness was supported through participant review of narrative summaries (14 of 24 participants provided substantive feedback), peer debriefing, reflexive journaling, and inter-coder agreement (κ = 0.83). Five themes and 15 subthemes were identified. Moral recognition was narrated as active, affectively mediated, and culturally embedded. A recurrent gap between moral judgment and moral action was attributed to hierarchical suppression of nursing voice and limited psychological safety. Servant leadership behaviours, empathic listening, moral mentoring, and ethical role modelling, as cumulative relational formation, functioned as moral scaffolding enabling ethical voice and action. Three emergent subthemes extended the framework: ethical role modelling as identity-level formation, spiritually grounded motivation rooted in Islamic accountability, and culturally sanctioned disclosure silence as a source of moral dissonance. Moral leadership in Saudi NICUs is a relational, contextually conditioned practice shaped by leadership behaviours, institutional structures, and cultural frameworks. Strengthening ethical infrastructure through leadership development, nurse-accessible ethics support, and competency frameworks embedding moral leadership as a professional standard is a priority for neonatal nursing in Saudi Arabia and comparable settings. Not applicable.
Pneumonectomy is associated with substantial perioperative morbidity and long-term cardiopulmonary function impairment. Therefore, avoiding pneumonectomy whenever oncologically feasible is an important goal in managing centrally located non-small cell lung cancer. This study evaluated the feasibility and oncologic outcomes of induction chemoradiotherapy administered to avoid pneumonectomy. We retrospectively reviewed patients with centrally located non-small cell lung cancer initially considered candidates for pneumonectomy but underwent induction chemoradiotherapy to reduce surgical margins between April 2010 and December 2025. Induction treatment comprised concurrent chemoradiotherapy with platinum-based doublet chemotherapy and thoracic radiotherapy. Radiological responses, surgical procedures, perioperative outcomes, pathological responses, and survival rates were analyzed. Eleven patients received induction chemoradiotherapy; nine underwent surgical resection, and two declined surgery. Pneumonectomy was avoided and complete resection (R0) was achieved in all patients. Sleeve lobectomy was performed in four patients and extended sleeve lobectomy in four patients. Pulmonary artery plasty was performed in three patients, two sleeve plasty and one wedge plasty. Postoperative complications occurred in four patients (44.4%), with no perioperative mortality. A major pathological response was achieved in eight patients (88.9%), including a pathological complete response in seven patients (77.8%). At a median follow-up of 30 months, the 3-year overall survival was 100%, the recurrence-free survival was favorable, and no locoregional recurrence occurred. Induction chemoradiotherapy may facilitate lung-sparing surgery in selected patients with centrally located non-small cell lung cancer. However, the small retrospective nature of this study and potential selection bias warrant cautious interpretation.
Near-infrared (NIR) organic afterglow probes are attractive for deep-tissue, high-contrast bioimaging, yet simultaneously achieving white-light excitation, long-lived NIR phosphorescence, and uniform nanoparticle fabrication remains challenging. Herein, we develop a bottom-up route to lattice-matched host-guest nanocrystals by incorporating a rigid phenylcarbazole host (BMC) with scaffold-matched, extended-conjugation guests (PyC or BPC). The resulting doped crystals show guest-dominated deep-red/NIR afterglow, with the longest-wavelength vibronic band reaching 762 nm and can be activated by visible light up to 475 nm, delivering an ultralong lifetime of 126.1 ms and a phosphorescence quantum yield of up to 2.7%. Importantly, the intrinsic homogeneity of the lattice-matched incorporation enables direct formation of monodisperse phosphorescent nanoparticles via simple bottom-up nanoprecipitation, avoiding the size heterogeneity and material loss typically associated with top-down crystal fragmentation. These nanoparticles exhibit negligible cytotoxicity and deliver bright, persistent deep-red/NIR emission under white-light excitation for high-contrast in vivo imaging.
Posterior urethral valves (PUV) represent the most common cause of lower urinary tract obstruction in male infants and are a leading contributor to chronic kidney disease (CKD) in children. This systematic review and meta-analysis aimed to synthesize and quantify the available evidence regarding the risk of long-term CKD in children with posterior urethral valves and to identify factors associated with adverse renal outcomes. A systematic review and meta-analysis were conducted in accordance with PRISMA and MOOSE guidelines. PubMed, Embase, Web of Science were searched from inception to January 31, 2026 for observational studies evaluating long-term renal outcomes in pediatric patients with posterior urethral valves. Eligible studies reported CKD outcomes, renal function decline, end-stage kidney disease, or need for renal replacement therapy with corresponding effect estimates or extractable data. Two reviewers independently screened studies, extracted data, and assessed methodological quality using Joanna Briggs Institute appraisal tools. Nine cohort studies published between 1988 and 2024 met the inclusion criteria, representing pediatric populations from Europe, North America, South America, and Africa. Across studies, children with PUV demonstrated a substantial risk of long-term CKD, with many progressing to renal impairment or end-stage kidney disease during extended follow-up. Meta-analysis of within-study comparisons demonstrated that PUV children with adverse prognostic features (absence of pop-off mechanisms, elevated nadir creatinine, or established renal dysplasia) had a significantly higher risk of CKD compared with PUV children with more favorable prognostic profiles (pooled OR: 1.44, 95% CI: 1.20-1.73). Although effect sizes varied, the overall trend consistently indicated adverse renal outcomes. Studies identified important prognostic factors, including renal dysplasia, elevated nadir creatinine, bladder dysfunction, and delayed diagnosis, while the presence of pop-off mechanisms was frequently associated with improved renal prognosis. Substantial heterogeneity was observed among studies (I² = 89%). Funnel plot assessment suggested no significant publication bias. This systematic review and meta-analysis demonstrates that children with posterior urethral valves remain at significant risk for developing long-term chronic kidney disease despite advances in early diagnosis and management. Future prospective studies are needed to refine prognostic models, standardize outcome reporting, and evaluate strategies aimed at preserving renal function and improving long-term health outcomes.
Up to now, a considerable number of borophosphates have been reported, despite the young history of this material class. However, detailed Tanabe-Sugano analyses to investigate the coordination strength of the host structures have barely been reported yet. Herein, the series Ca0.5M(H2O)2[B(PO4)2]·H2O with M = Ni, Fe was extended by introducing further metal cations with M = Mg, Mn, Co, Zn, Cd; the M atoms are coordinated octahedrally by oxygen and water. Thus, the reflection spectra for M = Mn, Co were elucidated by determining the Racah parameter and the ligand field splitting of the d-orbitals which revealed that borophosphates can be classified as weakly coordinating host materials. The crystal structure contains corner sharing borate and phosphate tetrahedra forming one-dimensional helical chains with water molecules inside those helices. Single-crystal data revealed the presence of systematically absent reflections in the original space group P6122 which was solved by losing the twofold axis, whereby the structure was refined in the trigonal subgroup P3121. Next to single-crystal XRD and UV-vis spectroscopy, the titled compounds were further characterised by powder XRD, FT-IR spectroscopy and thermal analysis.
Small-cell lung cancer (SCLC) accounts for 13-15% of lung-cancer diagnoses but nearly one quarter of lung-cancer-related deaths. Until 2015, the combination of platinum-etoposide chemotherapy, thoracic radiotherapy and prophylactic cranial irradiation (PCI) had kept median overall survival broadly stable at ≈ 12 months in extensive-stage (ES-SCLC) and ≈ 24 months in limited-stage (LS-SCLC) disease. We summarise the key therapeutic advances of the last decade. This is a curated narrative review. PubMed/MEDLINE, Embase, ClinicalTrials.gov, FDA and EMA releases and ASCO/ESMO/WCLC abstracts published between January 2015 and May 2025 were searched for phase II/III trials, regulatory approvals and biomarker studies in SCLC. Quantitative pooling was not performed. Practice-changing trials, selected pivotal phase II studies that led to regulatory approval, translational papers that re-defined the molecular taxonomy and informative negative trials were prioritised for in-depth discussion. A PRISMA-style flow diagram (Fig. 1) summarises the selection process. Consolidative thoracic radiotherapy improved 2-year OS in ES-SCLC responders (CREST: 13% vs. 3%; HR 0.84, 95% CI 0.69-1.01) and brain-MRI surveillance preserved cognition while replacing routine PCI in patients with ES-SCLC who had access to neuro-imaging. IMpower133 and CASPIAN established first-line chemo-immunotherapy: adding atezolizumab or durvalumab to platinum-etoposide extended median OS by ≈ 2-3 months (IMpower133: 12.3 vs. 10.3 months, HR 0.70, 95% CI 0.54-0.91; CASPIAN: 13.0 vs. 10.3 months, HR 0.73, 95% CI 0.59-0.91) and approximately doubled 18-month survival; 5-year OS now reaches 12-13%. Lurbinectedin produced a 35% response rate in platinum-sensitive relapse in a single-arm phase II study; the confirmatory phase III ATLANTIS trial was negative. Trilaciclib reduced severe chemotherapy-induced myelosuppression. Molecular profiling re-segregated SCLC into ASCL1- (SCLC-A), NEUROD1- (SCLC-N), POU2F3- (SCLC-P) and YAP1/inflamed-defined (SCLC-I) subtypes, supporting the development of subtype-directed trials. DLL3 has re-emerged as a target via the bispecific engager tarlatamab (DeLLphi-301: ORR 40%, mDOR 12 months) and next-generation antibody-drug conjugates. In LS-SCLC, durvalumab consolidation up to 24 months after chemoradiotherapy improved median OS from 33.4 to 55.9 months (ADRIATIC; HR 0.73, 95% CI 0.57-0.93). Maintenance lurbinectedin plus atezolizumab more than doubled median PFS after induction chemo-immunotherapy in IMforte (5.4 vs. 2.1 months; HR 0.54, 95% CI 0.43-0.67) and improved median OS (13.2 vs. 10.6 months; HR 0.73, 95% CI 0.57-0.95). Several phase III trials in this period were negative (KEYNOTE-604, CheckMate-451, CheckMate-331, SKYSCRAPER-02, ATLANTIS, TAHOE, MERU). SCLC therapy has shifted from uniform cytotoxic treatment to a tiered, mechanism-driven algorithm that incorporates PD-L1 blockade, targeted cytotoxics, myeloprotection and refined radiotherapy, raising long-term survival above 20% in selected populations. From a European-practice perspective, current best practice is platinum-etoposide plus a PD-L1 inhibitor for treatment-naïve ES-SCLC, thoracic consolidation radiotherapy in selected responders, lurbinectedin or DLL3-directed clinical trials at relapse, and durvalumab consolidation after chemoradiation in LS-SCLC. Outstanding challenges include a low absolute survival gain from chemo-IO, the absence of validated predictive biomarkers, lineage plasticity, and unequal global access to new agents.
Fucoidans are sulfated polysaccharides from brown algae with promising anticancer properties, but the specific structural determinants underlying their biological effects remain poorly defined. Here, four different GH107 family endo-fucanases were used to depolymerize Fucus evanescens fucoidan (FeF), yielding eight high- (HMP) and low-molecular weight (LMP) derivatives differing Mw and sulfation. Enzymatic depolymerization revealed the hidden structure regularity of FeF fucoidan, characterized by extended mostly regular sites of [→4)-α-L-Fucp2S-(1 → 3)-α-L-Fucp2S-(1→]n and [→4)-α-L-Fucp2S-(1 → 3)-α-L-Fucp2,4S-(1→]n linked by less regular sites rich in 2,3-di-sulfated L-fucose residues. The ability of FeF and its enzymatic derivatives to inhibit the colony growth of human cancer cell lines (MCF-7, MDA-MB-231, DLD-1, HuTu80, and SK-MEL-28) was further tested. Reduction in FeF molecular weight (Mw) proved critical for inhibiting colony growth of DLD-1 and MCF-7 cells, with native FeF most potent and LMP derivatives showing practically no effect. In contrast, certain HMP or LMP derivatives with reduced Mw and optimized sulfate content and/or sulfation pattern (especially 2,4-di-sulfated) exhibited enhanced activity against MDA-MB-231, SK-MEL-28, and HuTu 80 cell lines compared to native FeF. Additional EGF-treatment was found to alter the sensitivity of certain cancer cells to specific structural motifs of fucoidans. Certain HMP and LMP derivatives also demonstrated enhanced chemopreventive effects against EGF-induced JB6 Cl41 transformation. These findings reveal that structural determinants of fucoidan anticancer effects differ not only by cancer cell type but also by exogenous or endogenous factors modulating cellular responses. These data further demonstrate the efficacy of specific endo-fucanases in tailoring native fucoidan structure to modulate its biological activity.
Cervical cancer remains a major public health concern in Sarawak, East Malaysia, which reports the highest incidence in the country. Prophylactic human papillomavirus (HPV) vaccination programme currently uses bivalent (2 v) and quadrivalent (4 v) vaccines targeting HPV16 and 18 (and additional low-risk HPV6 and 11 for 4 v). However, the alignment of these vaccines with locally circulating high-risk HPV (hrHPV) genotypes is poorly understood. We conducted a serial cross-sectional study involving 1,108 women in Sarawak, Malaysia from 2018 to 2024. Self-collected high vaginal swabs were analyzed using the Anyplex™ II HPV HR Detection Kit for 14 hrHPV genotypes. Demographic data and vaccination status were collected. Descriptive statistics and Chi-square tests were used to evaluate associations between hrHPV positivity and demographic variables. The overall hrHPV prevalence was 10.2% (95% CI: 8.6-12.1%). Among positive cases, 87.6% had single, 10.6% dual, and 1.8% triple genotype infections. The most frequent genotypes were HPV18 (19.2%), HPV52 (16.9%), HPV39 (14.6%), and HPV51 (10.0%). Genotypes covered by the 2 v/4 v vaccines (HPV16/18) accounted for 25.4% of infections, and those included in the nonavalent (9 v) vaccine extended coverage to 56.2%. Notably, 43.8% of infections were due to non-2v/4 v/9 v vaccine genotypes. No significant associations were found between HPV positivity and age group, ethnicity, geographic division, or vaccination status. Our findings indicate a mismatch between current HPV vaccines and the prevalent hrHPV genotypes in Sarawak. While the 9 v vaccine offers improved coverage, a substantial proportion of infections are due to non-vaccine types. Strengthening molecular surveillance, improving access to screening, and addressing vaccine-derived complacency are critical to achieving cervical cancer elimination in this region.
Pushing lithium cobalt oxide (LCoO2) toward extremely high-voltage operation up to 5V is critical to boosting a battery's energy density for future compact electronics. However, its degradation mechanisms at such extreme voltages remain unexplored. Here, we employ machine-learning-aided super-resolution electron microscopy to directly visualize, at atomic resolution, how LCoO2 structurally deteriorates under 5 V for the first time. We discover that deep delithiation activates global deformation in which in-plane shear breaks the O3 lattice into nanoscale mosaics of O1 and reoriented O3 domains, while out-of-plane distortions drive cracking and kinetically trapped structural motifs. Upon extended cycling, these coupled chemomechanical processes evolve into a frustrated surface architecture comprising intertwined misoriented domains and antiphase boundaries. Building on these mechanistic insights, we deliver a proof-of-concept demonstration that rationally designed codoping provides a targeted route to mitigate the coupled deformation and phase-degradation cascade, markedly pushing the cycling stability of LiCoO2 toward unprecedented ultrahigh voltage. Our work establishes a new paradigm for materials optimization by leveraging atomic-scale diagnostics to mitigate degradation at its origin.
To achieve sufficient dispersion stability, ionizable groups such as dimethylolpropionic acid (DMPA) are often incorporated into the framework of water-based polyurethane dispersions (PUDs). As a weak acid, this group exhibits pH-dependent dissociation, which directly influences the degree of electrostatic repulsion between two particles. To gain deeper insights into the structure-stability relationship of PUDs, we synthesized numerous samples with different soft segments (polyether, polyester, and polycarbonate polyols) and varying contents of DMPA according to the acetone process. The dissociation behavior of the carboxyl groups and the particle charge were characterized by potentiometric acid-base titration, and the corresponding titration curves were fitted assuming multiple functional groups with adaptable acid strengths. To determine the surface potentials, electrokinetic measurements as a function of electrolyte concentration were performed and analyzed by the hard particle theory considering the relaxation effect. Dispersion stability was examined by means of the critical coagulation concentration (ccc) and evaluated according to the DLVO and XDLVO theory. Hamaker constants were determined based on contact angle data of the respective PU films with an apolar test liquid using the van Oss-Chaudhury-Good theory. The study shows that not all carboxyl groups incorporated into the polymer backbone can be detected by potentiometric titration. In addition, data from titration curves are best fitted when at least two functional groups with different acid strengths are assumed, indicating a nonuniform charge distribution in a peripheral layer and hindered dissociation. Interestingly, early DMPA incorporation during the prepolymerization step has a significant effect on the charge localization in the PUD particles. Compared to PUDs, in which the ionizable groups were incorporated during the final chain extension step, the proportion of charge groups in the particle interior increases significantly. However, these differences hardly affect the determined surface potentials and dispersion stabilities. Similar to a recent study, the surface potentials decrease slightly with increasing DMPA content, which is a result of the decreasing particle size. As expected, the ccc values increase with rising DMPA content, but in particular, they show a strong influence of the polyol component. The analysis of our data indicates that the DLVO approach should be extended by considering an additional attractive interaction energy, which is probably based on the hydrophobicity of the polymer components.
In recent years, protein language models (pLMs) and graph neural networks (GNNs) have demonstrated powerful expressive and reasoning capabilities in modeling protein-RNA/DNA interactions. However, existing methods, which use simple graphs to describe the relationships between residues, struggle to effectively capture the high-order, multi-body residue interactions present in protein-nucleic acid complex structures. In fact, spatially continuous but sequence-wise discontinuous residues often cooperatively determine nucleic acid binding capacity. In this study, we present IKANbind, a computational approach that combines hypergraph representation learning and interpretable Kolmogorov-Arnold Networks (KANs), for identifying nucleic acid binding residues (NBRs) in proteins. By combining the advantages of pLM, hypergraph neural networks and symbolic KAN, IKANbind outperforms existing methods on multiple NBR benchmark datasets. We also demonstrated that the pLM used in IKANbind can implicitly learn the physicochemical properties of binding residues, such as charge and hydrophobicity. In addition, the symbolic KAN, which uses a unique weighted mechanism of decomposable basis functions, can accurately identify the features with the greatest contribution to NBR recognition. We found that polarity and charge make greater contributions to NBR prediction than other physicochemical properties or evolutionary information. Finally, IKANbind achieves promising performance when extended to other ligand-binding residue prediction tasks. IKANbind is freely available at https://github.com/yangfengzhuguet/IKANBind. Supplementary data are available at Bioinformatics online.
To compare the effectiveness of different treatment strategies after unplanned surgery for myxoid liposarcoma (MLS) and explore the clinical value of salvage therapy versus planned treatment following unplanned resection. The clinical data of 37 MLS patients admitted between June 2014 and June 2024 who met the selection criteria were retrospectively analyzed. Patients were divided into three groups based on initial treatment status: the unplanned treatment group (group A, 14 cases, transferred after benign tumor excision without further treatment at external hospitals, presenting with local recurrence), the salvage planned treatment group (group B, 10 cases, transferred within 1 month after benign tumor excision at external hospitals), and the planned treatment group (group C, 13 cases, transferred without prior treatment or only after biopsy). No significant difference ( P>0.05) was observed among the three groups in baseline characteristics including age, height, weight, and maximum preoperative tumor diameter. Tumor recurrence or metastasis time were recorded. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method with intergroup comparisons. All 37 patients were followed up 19-193 months (mean, 67.4 months). Group A exhibited higher tumor recurrence (28.6%) and metastasis rates (35.7%) than group B (10.0%, 10.0%) and group C (0, 23.1%), with significant differences in recurrence rates ( P<0.05), no significant differences existed between groups B and C ( P>0.05); metastasis rates showed no intergroup significance ( P>0.05). Group A demonstrated lower 1-/3-/5-year DFS (71.4%, 42.9%, 21.4%) than group B (100%, 88.9%, 74.1%) and group C (92.3%, 83.9%, 71.9%), with significant differences ( P<0.017), no significant difference existed between groups B and C ( P>0.017); 3-/5-year OS showed no intergroup significance ( P>0.05). Patients with MLS should undergo standard extended resection and individualized adjuvant radiotherapy and chemotherapy as soon as possible after unplanned surgery to significantly reduce the local recurrence rate. In view of the high risk of extrapulmonary metastasis, a comprehensive preoperative assessment of metastasis is required. 比较黏液样脂肪肉瘤（myxoid liposarcoma，MLS）非计划手术后不同治疗策略的疗效，探讨非计划手术后补救性治疗与计划性治疗的临床价值。. 回顾性分析2014年6月—2024年6月收治且符合选择标准的37例MLS患者临床资料。根据入院时治疗情况分为3组：非计划治疗组（A组，14例，外院按良性肿瘤切除后未进一步治疗，局部复发后转入）、补救计划治疗组（B组，10例，外院按良性肿瘤切除后1个月内转入）、计划治疗组（C组，13例，未经治疗或仅行活检后转入）。3组患者年龄、身高、体质量、术前肿瘤最长径等基线资料比较差异均无统计学意义（ P>0.05）。记录患者肿瘤复发或转移时间等；采用Kaplan-Meier法计算总生存率（overall survival，OS）及无病生存率 （disease-free survival，DFS）并进行组间比较。. 37例患者均获随访，随访时间19～193个月，平均67.4个月。A组肿瘤复发率（28.6%）和转移率（35.7%） 均高于B组（10.0%、10.0%）和C组（0、23.1%），复发率差异有统计学意义（ P<0.05）；B、C组间差异无统计学意义（ P>0.05）。3组间转移率无统计学意义（ P>0.05）。A组1、3、5年DFS（71.4%、42.9%、21.4%）均低于B组（100%、88.9%、74.1%）和C组（92.3%、83.9%、71.9%），差异有统计学意义（ P<0.017），B、C组间差异无统计学意义（ P>0.017）；3组间3、5年OS差异无统计学意义（ P>0.05）。. MLS患者在非计划手术后，应尽快行规范的扩大切除及个体化辅助放化疗，以显著降低局部复发率。鉴于其肺外转移风险极高，术前需全面评估转移情况。.