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Dual regulatory effects of medical bovine collagen sponge on macrophages in vitro
Medical bovine collagen sponges (MBCS) are extensively utilized in clinical settings for hemostasis and tissue augmentation owing to their superior biocompatibility, biodegradability and hemostatic properties. Nevertheless, their immunomodulatory influence on macrophage function remains largely unexplored. In this study, we systematically evaluated the effects of MBCS on RAW264.7 macrophages through comprehensive in vitro assays, including proliferation analysis, phagocytosis assessment, cytokine expression and angiogenesis evaluation. Our results demonstrate that MBCS significantly enhances macrophage proliferation and phagocytic capacity while potently stimulating VEGF secretion. Furthermore, MBCS-conditioned macrophage supernatants markedly promote endothelial tubule formation in vitro. Notably, MBCS moderately promotes inflammatory responses in resting macrophages, whereas pretreatment with MBCS effectively inhibits lipopolysaccharide (LPS)-induced pro-inflammatory reactions, as reflected by reduced production of TNF‑α, nitric oxide and CD86. These findings reveal the effects of MBCS on macrophages at the cellular level, providing experimental evidence and mechanistic support for its tissue-repairing functions.
The effect of squat training with different eccentric contraction tempos on lower limb muscle strength
Objective This study aims to investigate the impact of 8-week squat training with different eccentric contraction tempos on maximal squat strength, jump height, and sprint performance among university students majoring in sports training. Methods Thirty participants were randomly assigned to either the 4/0/X/0 group, the 2/0/X/0, or the self-selected eccentric, isometric and inter-repetition tempo group (V/V/X/V), performing tempo-specific loaded squat training twice weekly for 8 weeks. Maximal squat strength, 30-meter sprint performance, countermovement jump (CMJ), and squat jump (SJ) heights were assessed before and after the intervention. A two-way repeated-measures ANOVA and effect size analysis were used to evaluate the training outcomes. Results 1) For maximal squat strength, no statistically significant inter-group difference was detected (P > 0.05). All three groups exhibited significant within-group improvements relative to baseline (P < 0.05 to P < 0.01). Descriptive effect size analysis showed the magnitude of improvement ranked as follows: 2/0/X/0 group (ES = 1.45)> V/V/X/V group (ES = 0.85)> 4/0/X/0 group (ES = 0.64). 2) For CMJ height, both the 2/0/X/0 and V/V/X/V groups showed significant improvement compared to pre-intervention (P < 0.05), while the 4/0/X/0 group exhibited a significant decrease (P < 0.01). ES magnitudes followed the order: 2/0/X/0 group (ES = 1.07) > V/V/X/V group (ES = 0.30) > 4/0/X/0 group (ES = −0.90). 3) SJ height results mirrored CMJ trends, with ES values ranking:2/0/X/0 group (ES = 1.09) > V/V/X/V group (ES = 0.34) > 4/0/X/0 group (ES = −0.83). 4) In 30-meter sprint performance, the 2/0/X/0 group demonstrated significant improvement (P < 0.05), the 4/0/X/0 group showed significant decline (P < 0.01), and the V/V/X/V group exhibited no significant change. Effect sizes indicated significant improvement in the 2/0/X/0 group (ES = −0.76), no meaningful change in the V/V/X/V group (ES = −0.10), and a significant decline in the 4/0/X/0 group (ES = 0.63). Notably, despite significant gains in maximal strength, the 4/0/X/0 group displayed concurrent decrements in stretch-shortening cycle-based explosive performances. Conclusion Compared with the 4/0/X/0 and V/V/X/V tempos, the 2/0/X/0 tempo showed the most favorable improvement trend in lower-limb maximal strength, and induced significantly greater enhancements in explosive power performance.
Public parks utilization and citizen satisfaction in Bangkok Metropolitan: An integrated theoretical model for tropical urban health
Background Tropical megacities face escalating non-communicable disease burdens requiring innovative urban health solutions. Despite public parks’ critical role as health infrastructure, limited research exists on utilization patterns and satisfaction in tropical urban contexts, where extreme heat and humidity create unique challenges. The equitable distribution of park benefits across socioeconomic groups remains underexplored in Southeast Asian contexts, a gap this study directly addresses. Objective This study developed and validated an integrated theoretical model of public park utilization and citizen satisfaction in tropical environments, identifying key determinants and providing evidence-based recommendations for health-promoting urban design, with attention to socioeconomic and gender equity dimensions. Methods We conducted a sequential explanatory mixed-methods study combining the Social Ecological Model, Expectation-Disconfirmation Theory, and Place Attachment Theory. Data were collected from 1,200 park users across 30 Bangkok parks using four-stage stratified random sampling, supplemented by 30 in-depth interviews. Analysis included hierarchical regression, thematic analysis, and comprehensive validity assessment. Results Participants (58.3% female, mean age 35.9 years) visited parks 3.3 times weekly for 1.8 hours per session. Park quality emerged as the strongest satisfaction predictor (β = 0.401–0.607, all p < 0.001), followed by usage patterns and accessibility. The integrated model explained 61.7–68.5% of satisfaction variance, a relatively high figure that partly reflects the common-method effects inherent in self-report designs (see Limitations). All nine hypotheses were confirmed with strong correlations (r = 0.554–0.796). Climate-specific challenges included inadequate shade coverage (M = 2.96/5.0) and insufficient evening lighting (M = 2.98/5.0). Qualitative analysis revealed parks function as urban oases, social ‘third places,’ and community-building spaces, with heat protection identified as the primary accessibility barrier. Significant socioeconomic gradients were observed, with lower-income users reporting systematically lower satisfaction across all domains. Conclusions This study provides a comprehensive integrated theoretical model for tropical urban park utilization, indicating that strategic quality improvements are more strongly associated with satisfaction than quantity expansion. Climate-adaptive features—particularly heat protection and extended evening access—represent essential design requirements differing fundamentally from temperate guidelines. The findings indicate that park benefits are not equitably distributed, with implications for Bangkok Metropolitan Administration (BMA) policies including the 15-minute city park initiative.
Mitochondria‐Targeted Photodynamic Agents Drive Robust Pyroptosis by Caspase‐3/GSDME Activation and Cardiolipin Externalization
ABSTRACT Photodynamic therapy (PDT)‐induced pyroptosis has attracted considerable interest as a strategy for cancer therapy, yet rational design of photosensitizers (PSs) that efficiently elicit pyroptosis remains underdeveloped. Herein, we report mitochondria‐targeted supramolecular PSs that simultaneously activate the caspase‐3/gasdermin E (GSDME) signal pathway and promote cardiolipin (CL) externalization to drive robust PDT–induced pyroptosis. A series of BODIPY‐based supramolecular PSs, containing quaternary‐ammonium moieties and N‐containing aromatic heterocyclic substituents, were rationally designed for mitochondrial accumulation and ROS generation. Upon light irradiation, these PSs elicit pronounced pyroptosis. Transmission electron microscopy and Calcein AM/Co 2 + imaging indicate that the mitochondrial membrane is significantly damaged, which probably is a critical event in the induction of pyroptosis. Immunofluorescence and Western blot analyses further demonstrate that 1 O 2 ‐mediated lipid peroxidation activates the caspase‐3/GSDME pathway and promotes CL externalization, facilitating mitochondrial pore formation and amplified release of mitochondrial contents. This positive feedback loop sustains caspase‐3 activity and pore formation, committing cells to pyroptotic death. The PSs exhibit excellent antitumor efficacy in tumor‐bearing mouse models.
A simulation model to predict the most efficient way to utilise operational resources when vaccinating badgers against bTB
Bovine tuberculosis (bTB) is a disease carried by badgers that seriously impacts the health and productivity of cattle in the United Kingdom (UK). The UK government’s aim is to be officially TB-free in cattle by 2038 in England and badger vaccination is one approach that can be used to achieve this. We use a simulation model to compare the relative performance of different vaccination strategies (treatment every year, every second year and every third year) under different field conditions and assumptions about vaccine efficacy. Population density, disease prevalence and duration of vaccine-induced immunity substantially affected the outcome of vaccination. A vaccine strategy with lower frequency treatment was effective and offers operational efficiency as multiple areas can be treated near concurrently by a single vaccination team, potentially halving the cost per unit area. The information presented here may be used to guide operational managers and decision makers towards a more efficient strategy in a particular area and may provide an estimation of the likely success of the chosen strategy.
Asymmetric Reductive Three‐Component Annulation Reaction for Constructing Fused N‐Heterocycles With Contiguous Stereogenic Centers
ABSTRACT The development of efficient methods for the diverse synthesis of optically active fused N‐heterocycles is vital for advancing medicinal chemistry. Hydrodearomative annulation of weakly reactive azaarenes presents a promising yet challenging strategy to fulfil such a synthetic purpose. Herein, we report a reductive three‐component reaction for the construction of fused N‐heterocycles with contiguous quaternary and tertiary carbon stereocenters, enabled by a simple chiral phosphoric acid/PhSiH 3 catalytic system. A wide variety of isoquinolinium salts were transformed in combination with formaldehyde and N ‐alkyl anilines into the target products with good isolated yields (up to 88%), and high diastereoselectivities (>20:1 dr) and enantioselectivities (up to 96.5:3.5 er). The reaction proceeds through sequential hydrodearomatization, C 4 ‐methylation, and asymmetric annulation, in which the chiral phosphoric acid participates in both the formation of intermediates and the stereocontrolling steps. DFT calculations further reveal that the observed enantioselectivity arises from C–H···O interactions between the substrate and catalyst, with steric repulsion effects playing a decisive role.
Dietitian-led intervention to manage constipation in Parkinson’s disease: Study protocol for a parallel-group randomized controlled trial (NUTRI-GUT-PD)
Background Constipation is a frequent non-motor symptom in Parkinson’s Disease (PD). Standard care includes dietary and lifestyle guidance or the use of laxatives. Diet represents a promising non-pharmacological approach, but its management in PD is complex and goes beyond simple dietary recommendations. This study protocol aims to examine whether nutritional counseling delivered by a dietitian is more effective than usual care in reducing constipation symptoms in PD patients. Methods This 90-day randomized controlled superiority trial uses a parallel-group design. A total of 54 outpatients with PD without dementia and fulfilling the Rome IV criteria for functional constipation will be included. Baseline assessments comprise demographics, nutritional evaluation (anthropometric measurements and sarcopenia indicators), neurological assessment, and the Constipation Scoring System (CSS) scores. Participants will perform stool sample collection for microbiota analysis and will be requested to complete three 24-hour dietary recalls over the subsequent week. After baseline, participants will be randomly allocated to either the control group (usual care) or the intervention group (nutritional counseling delivered by a dietitian). At the first study visit, participants will deliver the stool sample and dietary recalls. The intervention will last for 90 days and will include one in person consultations and bi-weekly follow-up phone calls. Nutritional counseling will address four main topics: healthy eating, food processing, fiber and fluid intake, and levodopa interactions with diet. In addition, participants in the intervention group will receive an individualized diet plan. All baseline assessments will be repeated at the 90-day endpoint. The primary outcome is the change in weekly bowel movement frequency from baseline to day 90, measured through the stool diary. Secondary outcomes include CSS, changes in fecal gut microbiota, macronutrient distribution, diet quality, body composition and sarcopenia indicators. Trial registration number: NCT07213856.
Transient Polarized Cavities Mediate an Ultrafast and Stable Graphite Anode for Potassium‐Ion Batteries
ABSTRACT Conventional ester‐based electrolytes exhibit intrinsic limitations for potassium‐ion batteries (PIBs): ethylene carbonate is solid at room temperature, while propylene carbonate induces graphite exfoliation via solvent co‐intercalation and suffers from poor rate capability. To address these challenges, we design a dipole‐engineered electrolyte that enables the formation of transient polarized cavities upon K + desolvation. These cavities generate localized negative electrostatic potentials that attract incoming K + ions, effectively lowering the ion transport barrier. This mechanism not only enhances K + kinetics but also promotes the formation of a stable, ion‐conductive solid electrolyte interphase, enabling highly reversible K + (de)intercalation in graphite. As a result, the K||graphite half‐cell delivers a high capacity of 290 mAh g −1 at 50 mA g −1 with negligible decay over 16 months (> 1000 cycles), and retains 226 mAh g −1 even at 500 mA g −1 . This work reveals a cavity‐mediated ion transport mechanism that offers new insights for designing high‐rate, long‐life graphite anodes in PIBs.
A systems biology approach to find representative genes in Acute Myeloid Leukemia
In this study, we modeled gene expression profile data from Acute Myeloid Leukemia (AML) and healthy cases. At first, the GEO-GSE9476 dataset was processed, and a total of 341 genes were identified as differentially expressed genes (DEGs) in patients, and 599 DEGs in healthy individuals. Gene Ontology and pathway analysis on DEGs led to the identification of 5 Transcription Factors for patients and 3 for healthy cases. Analysis of the respective metabolic pathways revealed a common region in the metabolic pathway between AML and Tuberculosis (TB) that confirmed the validity of our procedure due to the consistency with similar reports. Upon PPI network analysis, Hub genes and three modules containing 41 up-regulated and down-regulated genes in AML patients were identified. Survival analysis on these genes results in reducing the number of identified effective genes into 3 upregulated ( ITGAM , ITGAL and CD163 ) and 5 downregulated genes ( MCM2 , MCM3 , RFC4 , RFC5 and FEN1 ). Finally, drug sensitivity analysis was performed on these genes demonstrating complexity in drug-resistance due to the pattern of gene expression. This knowledge could potentially enable personalized treatment approaches based on individual patient responses due to the epigenetics and life style which affect gene expression pattern.
Reactivity of a d <sup>2</sup> Mo(IV) Alkylidyne Fragment Bearing a PNCNP Pincer Ligand Toward Alkynes: Coordination and Catalytic Alkyne Metathesis
ABSTRACT Currently, almost all alkyne metathesis catalysts are based on high valent d 0 Schrock‐type alkylidyne complexes. Although non‐d 0 transition‐metal alkylidyne complexes are also common, to date, only Re(V) alkylidyne have been reported to be capable of catalyzing alkyne metathesis. Herein, the reactivity of a d 2 Mo(IV) alkylidyne fragment bearing a PNCNP pincer ligand toward alkynes was studied. A series of novel Mo carbyne‐alkyne complexes was synthesized and characterized. The incorporation of N‐Me moieties in the pincer ligand reduced the energy barrier of the metathesis process. Accordingly, the first example of a catalytic system for alkyne metathesis reaction involving a d 2 Mo(IV) alkylidyne fragment was developed.
Multivalent Antibody‐Recruiting Molecules for Targeted Immune‐Killing of Carbonic Anhydrase IX‐Expressing Cancer Cells
ABSTRACT Antibody clustering on the surface of cells enables recognition by Fc receptors on innate immune cells and activation of the complement cascade, resulting in elimination. This effect can be leveraged for cancer therapy by monoclonal antibodies that recognize a cell surface antigen, but can also be achieved by synthetic bivalent molecules that mediate ternary complex formation between a cancer cell and endogenous, that is, non‐externally administered, antibodies. We report on antibody‐recruiting molecules (ARMs) targeting carbonic anhydrase IX (CAIX)‐expressing cancer cells. CAIX, a marker overexpressed in many hypoxic tumors, was targeted using acetazolamide (AAZ) analogs, while dinitrophenol (DNP) analogs were used to recruit endogenous anti‐DNP antibodies. We synthesized both single‐ligand ARMs (SL‐ARMs) and multivalent dextran‐templated ARMs (dex‐ARMs). Our results showed that dex‐ARMs significantly outperformed SL‐ARMs in recruiting anti‐DNP antibodies to the cell surface of CAIX‐expressing cells. The multivalent dex‐ARMs demonstrated robust antibody recruitment even in the presence of competing ligands, suggesting the recruitment of multiple antibodies per dextran. Furthermore, dex‐ARMs effectively recruited endogenous antibodies from serum, inducing cancer cell killing by macrophages. This study establishes the foundational efficacy of dex‐ARMs and suggests their utility in enhancing immune responses against hypoxia‐associated tumor markers, providing a novel strategy for cancer immunotherapy.
Choroidal metastasis: Impact of primary tumors and age on survival - a single center analysis
Purpose The purpose of this study was to determine whether patient’s age and their primary tumor type act as independent predictors of their survival after a diagnosis of choroidal metastasis. Methods This retrospective single-center study (August 2013 – August 2025) included 70 patients with choroidal metastases. Clinical data and multimodal imaging were extracted from medical records. Tumor volume was calculated from ultrasound measurements. Patients were grouped according to primary tumor origin (lung, breast, or other primaries). Survival was compared between these three primary tumor groups and according to age. Group differences in continuous variables were assessed using ANOVA/Kruskal-Wallis testing, and survival distributions were analyzed with Kaplan-Meier curves. Patients were categorized into younger (<59.6 years) and older (≥59.6 years) groups for Kaplan-Meier survival analysis. Univariate and multivariate Cox regression models were performed to identify independent predictors of overall survival. Results Median overall survival was 71.6 weeks. Statistically significantly longer survival was found in patients <59.6 years (median 88.3 weeks; estimated 3-year survival 33.2%) compared with those ≥59.6 years (median 41.9 weeks; 3-year survival 16.8%; p = 0.037. Primary tumor group analysis showed a median survival of 94.4 weeks for breast cancer (estimated 3-year survival 38.3%), 52.7 weeks for lung cancer (9,5%), and 40.6 weeks for other primaries (19.7%). However, this difference was not statistically significant (p = 0.269). In multivariate Cox regression analysis, age ≥ 59.6 years (HR 2.10; p = 0.016) and >1 extraocular metastases elsewhere in the body (HR 2.53; p = 0.029) were independent predictors of mortality. Conclusion Survival in choroidal metastases is strongly driven by age and the number of extraocular metastatic sites at presentation. Our findings suggest that younger age and a lower metastatic burden are most reliable indicators for a more favorable prognosis.
The economic burden of Type 2 Diabetes by social determinants of health: A systematic review
Background The unequal distribution of resources in society generates social gradients that translate into health inequalities and differential use of health care resources and their costs. Non-medical factors such as employment, income, ethnicity and education impact the prevalence and treatment outcomes of patients with type 2 diabetes mellitus (T2DM); however, there is a scarcity of articles assessing the relationship between health inequalities and the economic costs of treatment. Therefore, we conducted a systematic review of published studies examining the cost differences of treating T2DM across social determinants of health (SDH). Methods We systematically searched MEDLINE, Embase, PsycINFO, EconLit, and NHS EED for original peer-reviewed articles that provided cost differences of treating T2DM by SDH: education, income, employment, residency and ethnicity. We grouped the studies by each SDH and calculated the percentage differences where possible between the lowest and highest ends of the gradient (education, income and employment). Residency was categorised as rural vs. urban and ethnicity as white or general population vs other ethnic minorities. Results We included 19 articles retrieved internationally from varying healthcare systems. Results were contextualised given the healthcare financing model. In countries with high out-of-pocket expenses, Black and Hispanic ethnic backgrounds and rural residence were associated with lower direct health care and costs likely to be determined by ability to pay rather than clinical need. Indirect costs such as lost productivity due to absenteeism were also lower in unemployed, and lower income groups. Conclusions There are evident health disparities in the direct and indirect economic consequences of T2DM. The effect of decreased healthcare use and costs on treatment outcomes needs to be further explored to inform policies to ensure healthcare delivery is based on clinical need rather than socio-economic factors.
Perylene Diimide‐Derived Bis(Macrocyclic) Ligand Affords Chiral Multinuclear Pd(II) Complexes via Direct Bay‐Region Palladation
ABSTRACT Macrocyclic ligands provide powerful access to structurally defined multi‐metallic architectures, yet direct π‐core metalation of imide‐functionalized polycyclic aromatic dyes remains difficult to control. Herein, we present the design and synthesis of a new nitrogen‐rich bis(macrocyclic) ligand ( 1 ) based on a perylene diimide (PDI) scaffold. Coordination of Pd(II) to this ligand triggers direct C─H palladation at the bay region of the PDI, yielding two distinct complexes—a bis‑Pd and a tetra‑Pd species ( 1‐Pd 2 and 1‐Pd 4 )—each featuring asymmetrically coordinated, bridged Pd centers within the macrocyclic cavities. Furthermore, palladation distorts the PDI core and induces conformational chirality in the macrocyclic framework. Ultrafast transient absorption measurements further reveal systematic changes in the excited‐state response across the series. In addition, OTTLE spectroelectrochemical studies show that direct palladation creates strongly redox‐responsive low‐energy optical states, with markedly enhanced near‐IR absorption in the reduced Pd complexes. This work provides a feasible synthetic route for the direct metalation of perylene diimide dyes, enabling strong dye‐metal electronic coupling and establishing such chiral multinuclear complexes as functionally tunable multi‐metallic π‐systems.
Semi‐Ionic C‐F Bonds Modulate Hydrogen Dynamics for Selective CO <sub>2</sub> ‐to‐CH <sub>4</sub> Electroreduction on Carbon Quantum Dots
ABSTRACT Electrochemical CO 2 reduction to CH 4 represents an attractive route for carbon recycling and energy storage, but remains limited by sluggish hydrogenation kinetics and ineffective management of reactive hydrogen species. Herein, we develop a molecular fusion strategy to synthesize fluorine‐rich carbon quantum dots (F1‐CQDs) featuring an unprecedented F content of up to 28.8 at. % in optimized F1‐CQDs. The catalyst delivers a CH 4 Faraday efficiency of 63.2% together with a CH 4 partial current density of 210.8 mA cm −2 in a flow cell. Combined in situ spectroscopy and theoretical calculations reveal that semi‐ionic C‐F bonds create abundant Lewis basic sites that selectively stabilize key CO 2 ‐reduction intermediates, while also regulating hydrogen dynamics by facilitating water activation and transient active hydrogen (*H) formation on neighboring carbon sites. This synergistic dual‐site functionality enhances the effective *H availability for stepwise hydrogenation without excessively favoring the competing hydrogen evolution reaction, as clarified by isotope labeling and *H‐scavenging experiments. This work establishes a clear structure‐activity relationship between C‐F bonding and catalytic performance, and provides a general design principle for metal‐free electrocatalysts through the coupled engineering of intermediate stabilization and hydrogen kinetics.
Prevalence, risk factors, and management practices of premenstrual syndrome among female university students in Lebanon: An observational cross-sectional study
Background Premenstrual syndrome (PMS) is common among women of reproductive age and may impair quality of life, academic performance, and social functioning. In Lebanon, data on PMS and its management among female university students remain limited. This study aimed to estimate the prevalence of PMS among female university students in Lebanon, identify risk factors, and recognize adopted management practices and their perceived effectiveness. Methods An observational cross-sectional study was conducted among female students at Beirut Arab University, Lebanon, between April 20 and May 8, 2026. Data were collected using a self-administered questionnaire assessing sociodemographic, menstrual, lifestyle, behavioral, psychosocial, and management-related factors. Premenstrual symptoms, social media addiction, and perceived stress were assessed using the Premenstrual Symptoms Screening Tool, Bergen Social Media Addiction Scale, and Perceived Stress Scale-4, respectively. Binary logistic regression was used to identify factors associated with moderate-to-severe PMS and premenstrual dysphoric disorder (PMDD). Results Among 1,062 participants, 497 participants screened positive for moderate-to-severe PMS (46.8%), and 175 had symptoms consistent with PMDD based on the PSST (16.5%). The most frequently reported moderate-to-severe symptoms were physical symptoms (69.7%), fatigue or lack of energy (68.8%), depressed mood or hopelessness (67.8%), and overeating or food cravings (66.2%). Academic absenteeism was reported by 37.2%. More than one-third of the participants with moderate-to-severe PMS and PMDD (39%) reported using pharmacological management practices, mainly non-steroidal anti-inflammatory drugs. However, less than half of medication users perceived these treatments as being very effective (45.8%). Higher odds of moderate-to-severe PMS were observed among current smokers (AOR = 1.61, P = 0.003), those with heavy menstrual bleeding (AOR = 1.58, P = 0.03), high meal skipping (AOR = 1.38, P = 0.03), high fast-food consumption (AOR = 1.34, P = 0.04), higher social media addiction scores (AOR = 1.31, P < 0.001), and higher perceived stress scores (AOR = 1.48, P < 0.001). Conclusion PMS was common among female university students in Lebanon and a considerable proportion experienced PMDD. In fact, lifestyle, behavioral, and psychosocial factors were associated with moderate-to-severe symptoms, highlighting the need for university-based awareness, screening, and counseling strategies that address modifiable risk factors and support appropriate management of premenstrual symptoms.
Formation Energy‐Dominated AB‐Stacking Structure Promotes Metal‐Covalent Organic Frameworks for High‐Performance Dual‐Ion Storage Potassium‐Ion Batteries
ABSTRACT The long‐range AA‐stacking structures present in most covalent organic frameworks (COFs) result in poor utilization of redox‐active sites and suboptimal electrochemical performance. Herein, we report a metallized COF (Cu@MCOF‐D) by pre‐synthesizing cyclic trinuclear copper clusters (Cu 3 ) and integrating them with 2,6‐diaminoanthraquinone (DAAQ). Formation energy calculations confirm that the material possesses a thermodynamically stable AB‐stacking structure, which effectively alleviates interlayer K + adsorption shielding and optimizes the interlayer K + diffusion kinetics. Results from ex situ transmission electron microscopy analyses under different charge/discharge states indicate that Cu 3 exhibits strong adsorption capability toward FSI − , while the ‒C═O/‒C═N‒ groups chemically bind K + , and together they synergistically enable dual‐ion storage. When applied as potassium‐ion battery (PIB) anode, the reduced diffusion barrier allows a high reversible capacity of 153.8 mAh g −1 at 20.0 A g −1 , and delivers 96.8% capacity retention after 6500 cycles at 5.0 A g −1 , demonstrating exceptional long‐term K + storage stability. In PIB full cells using potassium iron hexacyanoferrate as the cathode, a high energy density of up to 197.5 Wh kg −1 is achieved. Furthermore, by employing 3,4,9,10‐perylenetetracarboxylic dianhydride heat‐treated at 450°C as the cathode, outstanding cycling stability is realized, with a capacity retention of 93.2% after 2000 cycles.
Vehicle routing optimization and algorithms for instant delivery under customer loss mechanism
In the field of instant delivery, the mismatch between delivery resources and customer demands has led to increasingly significant customer losses. To address this issue, this study introduces the customer loss mechanism and constructs an evaluation function to screen out resource-intensive customers, thereby clarifying the scope of delivery services. Based on this, this study establishes the vehicle routing optimization model under the customer loss mechanism with the objective of minimizing the sum of vehicle fixed costs, variable routing costs, and time window penalty costs. An improved genetic algorithm is employed to solve this model. Case study results demonstrate that the improved genetic algorithm outperforms traditional genetic algorithms and tabu search algorithms in convergence speed, optimization capabilities, and stability, reducing total delivery cost by 36.25% and 4.18%, respectively, with zero delivery violations. Regarding model performance, when proactively excluding 8.33% of customers, the total delivery cost is reduced by 17.18%, primarily driven by the reduction in fleet size. Furthermore, large-scale experiments reveal a pronounced leverage effect: excluding a mere 5% of marginal customers counter-intuitively reduces both fleet size and travel distance, while a 10% loss yields an 18.39% total delivery cost reduction with zero violations, proving that the mechanism precisely screens out inefficient nodes rather than arbitrarily rejecting them. Sensitivity analysis further confirms the model’s robustness across varying resource tightness, demonstrating that proactive customer loss is a feasible and effective strategy for improving resource utilization through precise resource focusing.
Dearomative [3,3]‐Claisen Rearrangement of 2‐Indolyl Alcohols: An Efficient and General Protocol for Synthesizing 3,3‐Disubstituted Indolines and Related Indole Alkaloids
ABSTRACT Dearomative reactions of indoles have long been a focal point of research in organic synthesis due to their ability to transform planar molecules into three‐dimensional structures. Among these reactions, the dearomative indolic [3,3]‐Claisen rearrangement stands out, though it has been largely limited to two substrate classes: 2‐allyloxy indoles and 3‐indolyl alcohols. Herein, we report a practical and reliable dearomative Meerwein–Eschenmoser–Claisen rearrangement of 2‐indolyl alcohols, providing an innovative solution for the efficient construction of the widely observed structural unit of 3,3‐disubstituted indolines, prevalent in natural products and pharmaceuticals. This synthetic methodology features simple reaction conditions, broad substrate scope, good E/Z selectivity for products, and excellent chirality transfer from starting materials. The robustness of this methodology is demonstrated via the concise asymmetric total synthesis of the structurally complex alkaloid minfiensine, wherein the success of the total synthesis hinges on the strategic transformation of the dearomative indolic [3,3]‐Claisen rearrangement coupled with the palladium‐catalyzed regioselective α‐vinylation of carbonyl compounds.
Expanding High‐Fidelity Multiplexing in Ultrasensitive Single‐Molecule Protein Detection via Proximity Barcoding
ABSTRACT The human proteome presents a vast information reservoir for basic and diagnostics research, yet the low abundances of many proteins in biofluids pose an analytical challenge. While ultrasensitive methods such as digital enzyme‐linked immunosorbent assay have expanded the window of detectable proteins, multiplexing with high accuracy, sensitivity, and throughput remains limited by cross‐reactivity and signal readout channels. To address this challenge, we introduce PRO‐MOSAIX (PROximity‐barcoded Molecular On‐bead Signal Amplification for Individual MultipleXing), a high‐accuracy multiplex digital immunoassay platform that integrates ultrasensitive single‐molecule protein detection with proximity ligation. PRO‐MOSAIX generates “ON” signals only from matched affinity reagents in proximity, minimizing false positives from cross‐reactive binding. This approach overcomes the multiplexing ceiling imposed by fluorescence spectral overlap by employing a single signal readout channel and DNA barcoding. We further improve multiplexing fidelity by mitigating a secondary source of false positives from DNA‐based signal amplification. As a proof of principle, we establish and validate a 15‐plex PRO‐MOSAIX assay in human plasma, with low femtomolar sensitivities and high measurement accuracies. PRO‐MOSAIX is modular and utilizes common laboratory instrumentation with a high‐throughput flow cytometric readout, providing a broadly accessible tool across research and clinical labs and bridging the gap between analytical sensitivity and high‐order multiplexing.