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Anthraquinone‐Based Electron Reservoir‐Pump Photosensitizer Generating Radical Ion Pairs for Metabolism‐Targeted Photodynamic Therapy
ABSTRACT Type I photodynamic therapy (PDT) overcomes oxygen (O 2 ) dependence of type II PDT, but developing hypoxia‐efficient electron‐transfer photosensitizers remains challenging. Herein, we proposed an anthraquinone (AQ)‐based single‐component “electron reservoir‐pump” strategy to enhance the electron transfer ability of type I photosensitizers. In this molecular design, the AQ scaffold functioned as an intrinsic electron reservoir, while the electron‐rich tetraphenylethylene (TPE) served as an electron pump that actively donated electrons. The synergistic reservoir‐pump interaction enabled the photosensitizer AQTPE to undergo photo‐disproportionation and generate radical ion pairs: the anionic radical efficiently reduced O 2 to form superoxide (O 2 −• ), while the cationic radical oxidized key metabolic cofactor flavin adenine dinucleotide (FADH 2 ) to disrupt redox homeostasis and suppress fatty acid synthase (FASN)‐mediated metabolism. In contrast, control photosensitizers AQCN and AQNI bearing electron‐withdrawing substituents maintained singlet oxygen ( 1 O 2 ) generation. Theoretical calculations revealed that AQTPE possessed a markedly reduced singlet‐triplet energy gap (Δ E ST = 0.01 eV) and enhanced spin‐orbit coupling (7.538 cm −1 ), facilitating intersystem crossing. Notably, AQTPE nanoparticles exhibited potent type I photodynamic activity and robust tumor suppression even under hypoxic conditions. This study establishes a molecular electronegativity‐modulation framework for integrating electron reservoir‐pump systems within single‐component photosensitizers, offering a general design principle for next‐generation metabolism‐targeted and hypoxia‐tolerant photosensitizers.
‘Every box has been opened’: London botanic gardens digitizes seven million specimens
Daily briefing: Iron-Age human bones were made into tools before interment
Stereoselective Biotransformation: Transfer of Learning to Advance Drug Metabolism and Biocatalysis
ABSTRACT Chirality is an important determinant of drug action, as enantiomers can exhibit markedly different pharmacological and toxicological profiles. Although the importance of stereochemistry in drug efficacy is well established, its role in drug metabolism and disposition remains comparatively underexplored, despite the inherently stereoselective nature of drug metabolizing enzymes. Given the high prevalence of chiral drugs in clinical use and among newly approved drugs, a systematic evaluation of stereoselective drug metabolism is needed. Understanding stereoselective biotransformations has important implications for predicting drug disposition and response and may also inspire novel biocatalytic and biomimetic strategies to address challenges in enantioselective synthesis of chiral active pharmaceutical ingredients and their metabolites. In this Systematic Review, we examine current trends and practices in the investigation of stereoselectivity in drug metabolism, the key factors influencing stereoselective metabolism, and the associated challenges and opportunities. We highlight how biocatalytic approaches can improve stereoselective access to chiral metabolites, and how insights from drug metabolism and pharmacokinetics (DMPK) studies can inspire the development of novel biocatalytic and biomimetic synthesis routes. Transfer of learning and cross‑disciplinary collaboration between biocatalysis and DMPK scientists will be critical for accelerating progress in these areas and for addressing shared challenges, including stereoselectivity prediction.
Beyond the Pre‐Equilibrium Approximation: Consequences of Elementary Step (Ir)reversibility on the Mechanistic Interpretation of Tafel Slope
ABSTRACT The relationship between electrochemical potential and reaction rate—or Tafel slope—is fundamental to the study of multi‐step charge transfer reactions. However, despite its importance and ubiquitous use, Tafel slope is seldom interpreted outside of “cardinal” values. The mechanistic interpretation of cardinal Tafel slopes is predicated on the pre‐equilibrium approximation (PEA): that the path between the (catalyst) resting state and rate‐determining step is in equilibrium. This stringent approximation severely limits opportunities to elicit mechanistic information from electrochemical processes. In this Scientific Perspective, we broaden the existing framework for mechanistic interpretation of Tafel slope through a simple, universal equation that generally describes Tafel slope in terms of elementary‐step symmetry factors and approach‐to‐equilibrium (i.e., approach to PEA accuracy). The predictiveness and mechanistic utility of these theoretical developments are showcased through analysis of experimental data available in the literature for a broad range of electrochemical and thermochemical catalytic reactions, including O 2 , H 2 , Cl 2 , and CO redox. The learnings accrued in these case studies inform kinetic studies of all multi‐step charge transfer reactions and are particularly relevant for mixed‐potential‐driven mechanisms of thermochemical catalysis, which in recent years have been shown to be preponderant at metal‐liquid interfaces.
Subsurface Stabilization of Interstitial Pt Atoms on CeO <sub>2</sub> (111): Rethinking Single‐Atom Catalyst Architectures
ABSTRACT Single‐atom catalysts (SACs) offer maximal efficiency by stabilizing isolated metal atoms on oxidic supports. Platinum on cerium oxide (CeO 2 ) is a key SAC system, where adsorbed CO typically exhibits red‐shifted vibrational modes due to Pt back‐donation. Using polarization‐resolved IR spectroscopy on Pt‐deposited CeO 2 (111) single‐crystal surfaces, we do not observe CO vibrational bands below 2140 cm −1 at low coverages, indicating that the surface‐bound Pt atoms are not present in detectable amounts. DFT calculations demonstrate that this unexpected observation is consistent with Pt atoms occupying buried interstitial sites. Such subsurface single‐atom sites, not considered in previous studies, are thermodynamically favored at low coverages, adopt an unusual oxidation state, and are inaccessible to direct CO binding. Our findings challenge the prevailing assumption that single atoms remain surface‐bound and highlight the critical role of subsurface interstitial species, prompting a rethinking of how active sites in single‐atom catalysts are stabilized on reducible oxides.
Automatic early detection of pathological signs following primary total hip arthroplasty using radiographs, clinical scores, and comorbidities
The growing prevalence of total hip arthroplasty (THA) revisions, along with their generally poorer outcomes compared to primary procedures, emphasizes the urgent need for early detection of primary THA failure. This study proposes a model that integrates radiographic, clinical, and comorbidity data to automatically detect pathological signs within one year after primary THA. The dataset included two independent patient cohorts: the first comprised 400 patients, leading to 801 radiographs with pathological signs and 785 without; the second included 155 patients, resulting in 417 radiographs with pathological signs and 508 without. After preprocessing, the dataset was split into training, validation, and test sets. Three models were developed, one for each data type. A deep learning framework was applied to the radiographic data, while multiple machine learning classifiers were trained on the clinical and comorbidity data. Predictive probabilities were obtained for each subset and data type, and the final combined model was generated by averaging the predicted probabilities from all individual models. The final combined model achieved an F1 score of 0.72 (95% CI: 0.65–0.79), a balanced accuracy of 0.69 (95% CI: 0.63, 0.77), and an area under the curve (AUC) of 0.72 (95% CI: 0.65, 0.79) on the internal test set. On the external validation set, it achieved an F1 score of 0.66 (95% CI: 0.62, 0.70), a balanced accuracy of 0.62 (95% CI: 0.59, 0.66), and an AUC of 0.67 (95% CI: 0.62, 0.72). The results demonstrate the potential of the developed approach to automatically detect early pathological signs of THA, enabling virtual follow-up and potentially reducing the burden on clinicians.
The time sensitivity of aspirational interventions: Evidence from a role-modeling RCT
This paper investigates the short-run effects of an aspiration-raising intervention delivered as part of a randomized controlled trial among postgraduate students at a UK university during the Covid-19 pandemic. We document suggestive evidence, that a video-based role-modeling intervention led to an immediate increase in aspirations and a delayed increase in self-reported effort. However, both effects dissipated within a few weeks. Our findings suggest that timing and reinforcement are important considerations for the sustained effectiveness of aspiration-building strategies.
Selective Hydrogenation of Formamide to Methanol Over Supported Platinum Catalysts
ABSTRACT The rising global energy demand, driven by population and economic growth, continues to be met largely by fossil fuels. Consequently, atmospheric CO 2 concentration has increased from ∼280 ppm in the pre‐industrial era to over 430 ppm today, motivating integrated capture‐and‐conversion strategies that valorize CO 2 as a feedstock. Amines are widely employed for post‐combustion CO 2 capture due to their low cost, rapid kinetics, and reversible carbamate formation. These amine–CO 2 adducts can be hydrogenated to formamides and subsequently to methanol under mild conditions (<150°C), regenerating the amine. However, selective C─N bond cleavage during the formamide hydrogenation for efficient release of methanol without sorbent deactivation remains a key challenge. Here, we demonstrate that 1 wt% Pt supported on TiO 2 (commercial P25) catalyzes the conversion of 4‐formylmorpholine to methanol with up to 62% yield and 95% selectivity at 150°C. In situ characterizations and DFT computations reveal that strong interaction between dispersed Pt and the support promotes selective C─N hydrogenolysis. The catalyst also exhibits excellent stability. These findings establish a robust heterogeneous platform for combined CO 2 capture and methanol synthesis, highlighting the critical role of support‐induced electronic effects in controlling bond scission.
Sulfur‐Directed Construction of Vinyl Cyclopropanes from 1,3‐Dienes
ABSTRACT The stereoselective cyclopropanation of 1,3‐dienes remains a long‐standing challenge in the preparation of vinyl cyclopropanes (VCPs) due to the intrinsic electronic and steric bias of the diene scaffold. We report a sulfur‐directed strategy that enables highly site‐ and diastereoselective cyclopropanation of S ‐substituted 1,3‐dienes with diazo reagents under Cu‐catalyzed reaction conditions. This unprecedented approach overrides the innate reactivity of the 1,3‐diene through a thioether‐directed reaction mode, providing rapid access to a broad library of highly functionalized S ‐VCPs obtained as single regio‐ and diastereomers. Preliminary mechanistic studies indicate a pericyclic cascade involving a 6π‐electrocyclization and a [2,3]‐sigmatropic rearrangement and postmodifications permit streamlined access to complex VCPs that remain inaccessible through conventional cyclopropanation techniques.
Not an infection: Endogenous circoviral elements underlie BFDV detections in Old World vultures
Circoviruses (family Circoviridae) are small, single-stranded DNA viruses known to infect a broad range of bird species. The Beak and Feather Disease Virus (BFDV), typically associated with parrots, has occasionally been reported in unrelated avian taxa, raising questions about host range and potential spillover. We investigated BFDV-like sequences in three sympatric vultures breeding in Spain (Egyptian vulture Neophron percnopterus , cinereous vulture Aegypius monachus , and griffon vulture Gyps fulvus ). PCR screening revealed low and inconsistent prevalence in Egyptian vultures (7.4%, n = 163) and cinereous vultures (2.9%, n = 47), and absent in griffon vultures (n = 35). Phylogenetic analyses identified nine highly divergent haplotypes spanning three distinct clades, with no structure by species, geography, or year, and no evidence of nest- or territory-level transmission. These patterns contradict expectations for an actively circulating virus and instead suggest that the sequences represent endogenous circoviral elements (ECV) integrated into the host genome. The absence of clinical signs, except in one inbred Egyptian vulture nestling (offspring of a brother-sister mating), indicates these elements are non-pathogenic. Our findings demonstrate that BFDV detections in non-psittacine birds often reflect genomic remnants rather than active infections. This reinterpretation underscores the need to combine molecular surveillance and evolutionary genomics to distinguish actual infections from viral relics.
Research on optimization of train routing problem for railway hubs considering passenger demand
The railway hub with multiple stations has been more common with the expansion of the railway network. It is imperative to investigate the utilization of multiple stations to meet the travel demand of urban residents. This paper focuses on railway hubs and abstracts the division of labor among multiple stations as an optimization of train routing problem. A mixed integer linear programming model is constructed to minimize the total cost of trains and passengers, with the number of stops, capacity of railway lines and station tracks, and passenger demand of traffic zones considered as constraints. A case study based on a multi-station railway hub is implemented to evaluate the effectiveness of the optimization model. Compared with the other two scenarios, the total cost of the optimization results is reduced by 0.1% and 2.7%. Meanwhile, the proposed optimization scheme also achieves a more balanced and efficient utilization of railway line and station track capacity. Furthermore, the research also proposes several operationally feasible recommendations for railway department to support making division of labor scheme for railway hubs.
Interdependent relationship between depression and Internet gaming disorder in parent-child dyads: The mediating role of family relationship and gaming time
Background and objective A well-established link exists between depression and Internet gaming disorder (IGD) at the individual level, while it remains unexplored within the family system. This study aims to investigate the interdependent relationship between parent and adolescent depression and IGD, and to identify the potential mechanisms. Methods A cross-sectional dyadic study was conducted with adolescents and their parents (primary caregiver) in Hong Kong. Adolescents completed anonymous surveys in classrooms, and parents completed online surveys via WhatsApp or phone interviews. The Actor-Partner Interdependence Model (APIM) and Actor-Partner Interdependence Mediation Model (APIMeM) were utilized to test the interdependence and mediators between depression and IGD in parent-child dyads, respectively. Results A total of 1,277 parent-child dyads were included. Depressive symptoms in parents (β = 0.072) and adolescents (β = 0.273, both p < 0.05) were positively associated with their own IGD symptoms (actor effect). Adolescent depressive symptoms were positively associated with parental IGD symptoms (β = 0.078, p < 0.05). Family relationships and adolescent gaming time mediated the association of adolescent depressive symptoms with adolescent IGD symptoms (indirect effect accounting for 21.5%) and parental IGD symptoms (74.3%). Conclusions Adolescent depressive symptoms were positively associated with their own and parental IGD symptoms, which were mediated by adolescent-reported family relationships and adolescent gaming time. The influence of adolescents’ mental health problems on parents’ problematic behaviors within the family system should not be overlooked.
Exploring how hospital based green spaces support stroke rehabilitation: A mixed methods multiple case study protocol
Background In-patient treatment and rehabilitation after stroke represent an important period for recovery, yet recommended levels of rehabilitation activity are challenging to achieve, and many patients remain inactive and at risk of low mood. Research in other conditions suggests that the use of green spaces can benefit in-patients, providing opportunities for activity and social interaction, and improving mood and wellbeing. However, little is known about the use of green spaces post-stroke. Aim To explore how, for whom, and under what conditions hospital based green spaces influence recovery, wellbeing and engagement with rehabilitation among stroke in-patients. Methods A mixed-method multiple case study will involve three hospital sites with different types of green spaces including those used for therapy, those newly designed for stroke survivors, and long-established spaces. Data collection will include gathering of contextual data (documentary analysis, mapping of the green space, interviews with green space designers and informal survey) to understand the setting, design, rationale, and maintenance; behavioural mapping (10-day period, two seasons per site) to understand usage; and semi-structured interviews with 45 in-patients and their visitors (including those who have and have not used the green space) and 30 multidisciplinary staff, to understand their experiences. Interview data will be analysed using the Framework approach. Mixed methods data will be integrated within and across cases to develop and refine a programme theory explaining how green space could support stroke recovery and wellbeing. Programme theory will be refined by expert groups of stroke survivors, carers and staff in three other locations. Discussion This study will generate a transferable programme theory and context-sensitive recommendations to inform the design, implementation and evaluation of green space in stroke care. We will disseminate findings widely to relevant audiences to influence future policy and practice.
Neuromuscular changes during a four-week individualized in-season strength-training program based on the dynamic strength index in youth basketball players: A quasi-experimental study
The dynamic strength index (DSI) is commonly used as a neuromuscular profiling metric to inform individualized strength-training decisions; however, evidence describing short-term in-season changes in DSI and constituent neuromuscular variables in youth team-sport athletes remains limited. This quasi-experimental applied study quantified neuromuscular changes during a four-week individualized in-season strength-training program in 21 youth basketball players (age: 16.4 ± 1.3 years). Players were stratified into high (>0.57), neutral (0.45–0.57), or low (<0.45) baseline DSI tertiles to prioritize training emphasis (maximal strength, mixed, or ballistic/plyometric, respectively). Participants completed three individualized sessions per week alongside regular basketball training. Pre- and post-intervention measures included countermovement jump (CMJ) height and peak force, isometric squat (ISOBelt) peak force, and estimated one-repetition maximum (1RM) back squat. DSI was subsequently calculated from CMJ and ISOBelt peak force values. The high DSI tertile showed increases in ISOBelt peak force ( p = 0.004, d = 2.10) and estimated 1RM back squat ( p = 0.002, d = 1.84), accompanied by a reduction in DSI ( p < 0.001, d = −1.56), whereas CMJ outcomes showed no statistically significant changes across tertiles (all p > 0.05). The neutral tertile showed an increase in estimated 1RM back squat ( p = 0.002, d = 0.89), although no significant interaction effects were observed. During the competitive season, DSI-based profiling was associated with distinct within-tercile neuromuscular changes over four weeks; findings should be interpreted as observational outcomes within an applied in-season context and may assist practitioners in guiding individualized in-season strength-training prioritization.
Prevalence, outcomes, and predictors of mortality among adult intensive care unit patients with sepsis at a Tertiary Hospital in Tanzania: A prospective cohort study
Background Sepsis continues to pose a significant global health challenge, particularly in low- and middle-income countries, which face a disproportionate burden of sepsis and sepsis-related deaths. The estimated prevalence of sepsis and sepsis-related mortality is higher in intensive care units than in hospitals overall. The burden can be higher in tertiary referral centers that receive patients from different regions. This study aimed to determine the prevalence of sepsis, its outcomes, and the factors associated with these outcomes among adult patients admitted to the Intensive Care Unit (ICU) of the Muhimbili National Hospital (MNH) in Tanzania. Methodology This prospective cohort study was conducted over a period of six months from May 16 to November 16, 2023, at MNH. A total of 248 patients were admitted during the study period and screened for sepsis on admission or for the development of sepsis during their ICU stay. Sepsis was defined according to the Sepsis-3 criteria as a suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥2 within 24 h of ICU admission. Proportions were used for descriptive statistics, and modified Poisson regression analysis was used to identify independent predictors of mortality at a 95% confidence interval, with P < 0.05 indicating statistical significance. Results The prevalence of sepsis was 41.5%. The respiratory system was the most common source of infection (32%), and 22.3% of patients had more than one infection site. The ICU mortality rate was 55.3%, with 35% of patients developing systemic complications during their ICU stay. Factors independently associated with mortality included multiple comorbidities (aPR 3.35, 95% confidence interval [CI], 1.20–9.32; p = 0.021) and a higher SOFA score (aPR 7.08, 95% CI 3.48–14.4; p < 0.001). Early initiation of antibiotics was independently associated with improved survival (aPR 0.47, 95% CI 0.27–0.84; p = 0.011). Conclusion This study revealed a high prevalence of sepsis and sepsis-related mortality in the ICU. A high SOFA score and multiple complications were independent predictors of mortality. Early initiation of antibiotic therapy was an independent predictor of survival. This underscores the importance of early treatment, close monitoring, and aggressive management in patients with predictors of poor outcome.
Inefficiency and inequity of the law review submission system
Where a legal scholar works shapes publication outcomes nearly as much as what they write. Law reviews, the primary publication market for legal scholarship in the United States, are run by student editors who face thousands of submissions for a handful of slots and rely heavily on institutional prestige as a proxy for article quality. We build a calibrated agent-based simulation of this market and benchmark it against deferred acceptance, a centralized matching algorithm used in markets like medical residencies. The simulation predicts severe misallocation: more than 60% of top-tier placements differ from what centralized signal-based matching would produce, and the rank correlation between article quality and journal prestige is 0.45 versus 0.79 under centralized matching. Which system produces better placements overall depends on how many authors are competing for how many slots. As competition intensifies, the current system’s disadvantage grows, with the model predicting up to 13.4% loss in match quality. Partial reforms like extending deadlines have negligible effects; in the simulation, the primary source of inefficiency is the decentralized structure of the market itself. The simulation also reveals that credential dependence produces inequity that persists even among articles of comparable quality: authors from prestigious institutions receive markedly better placements regardless of the matching mechanism. Centralized matching fixes the sorting problem but not this equity problem, because prestige bias is embedded in editorial signals and would require changes to how articles are evaluated, not just how they are assigned.
Stability of the two enveloped viruses NDV LaSota and YF-ZIKprM/E to support process development
Building on the established use of enveloped viral vectors, like lentivirus and vesicular stomatitis virus, we investigated the stability of the oncolytic Newcastle disease virus LaSota strain and the chimeric construct of a Zika vaccine candidate YF ZIKprM/E. These vectors are currently being developed for the treatment of solid tumors, such as melanoma and glioblastoma, and for vaccine initiatives, respectively. Virus stability is a critical attribute during cell culture-based virus production and also relevant for downstream processing, storage of the produced material, final vaccine storage and shelf life. Therefore, temperature and pH stability were tested as important parameters during upstream processing and freeze-thaw cycles were tested in context of laboratory-analytics. In this study, both viruses exhibited strong stability of the infectious virus titer when subjected to repeated freeze-thaw cycles. However, exposure to temperatures above 22°C substantially reduced the infectious titers, indicating sensitivity to elevated temperatures. To improve viral stability during storage, we investigated the use of sucrose as a stabilizing excipient. While this did not result in significant improvements for YF-ZIKV, an extended half-life for NDV at room temperature was observed. The observed half-life values of upstream material from NDV of 2.6 h and 2.8 h for YF-ZIKV at 37°C demand consideration of changes to the process design, such as the implementation of a perfusion process to enable continuous, cooled virus harvesting.
A scoping review of force plates in female soccer: The utility, existing practice and identification of knowledge Gaps
Female soccer has grown exponentially with increasing funding, participation and competition. Force plates enable high resolution force-time assessment using isometric and dynamic tasks for acute or longitudinal monitoring, and profiling performance and injury risk. However, more research has been conducted in male soccer players compared to females with the utility of force plates in female soccer yet to be reviewed. The purpose of this scoping review is to review existing research using force plates in female soccer describing the utility of force plates, methods used, reported metrics and to identify gaps in our current understanding. A literature search was conducted using PubMed, Google Scholar, Medline, and Cinahl using the following search terms: “girl*” OR “female*” OR “women*” AND “football*” OR “soccer*” AND “force plat*” AND “ jump” OR “isometric” AND (“multi joint*” OR “single joint*” OR “plantar flex*” OR “knee*” OR “hamstring*” OR “knee flex*” OR “hip exten*” OR “posterior chain*” OR “drop*” OR “rebound*” OR “stiffness*” “power*” OR “strength*” OR “counter*movement*” OR “dominant*” OR “non dominant*”). Sixty-three studies were eligible with most studies investigating senior elite players during dynamic tasks. The bilateral countermovement jump was the most common test followed by pre-planned change of direction and the isometric mid-thigh pull. Force plates were mostly used for performance assessment/ sex comparison research designs, followed by acute monitoring. Peak force was the most reported metric across all studies and jump height was most reported in studies investigating jumping. Most researchers used force plates in laboratory settings relating to change of direction and landing tasks with limited research conducted in applied settings and at youth level. Therefore, future researchers should focus on field-based assessments aiming to provide benchmarks and prospectively track players for injury as to support the health and performance of female soccer players at all levels of competition.