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The COVID-19 pandemic placed junior physicians at the forefront of clinical care under extraordinary conditions, compelling them to navigate overwhelming workloads, and emotionally challenging and ethically complex situations. This qualitative study explores how these experiences shaped their perceptions of self-sacrifice, as interpreted through the lens of the social contract as expressed in foundational frameworks of medical professionalism, such as CanMEDS. Semi-structured interviews were conducted with 17 junior physicians at two emergency hospitals in Sweden, and the data were analyzed using reflexive thematic analysis. The findings reveal that junior physicians experienced significant physical and psychological strain, including fear of infection, exhaustion, and strain on personal well-being and relationships. While participants demonstrated strong dedication to patient care, they also voiced resistance to the implicit expectation of unlimited self-sacrifice embedded in professional ideals. These experiences not only tested their endurance but also re-shaped how they understood the balance between altruism, personal limits, and professional duty. Expectations of self-sacrifice are embedded during medical education, yet our findings suggest that these norms are both reproduced and critically questioned as physicians transition into practice, when they are confronted with the lived realities of clinical work. Importantly, the study indicates a contextual re-negotiation of how altruism and self-sacrifice are perceived, with junior physicians in this material challenging inherited ideals of heroic endurance. The extraordinary pressures of the pandemic appeared to accelerate this process, bringing these reflections to the surface earlier and more forcefully than might otherwise have occurred. The study highlights the need to balance professional commitment with sustainable support structures, and points to the importance of renegotiating the social contract between physicians and society in light of evolving professional realities.

Pseudomonas aeruginosa has an extraordinary capacity for resistance emergence during treatment, even with newer antipseudomonals. There is a gap in understanding how resistance mechanisms affect the time-course of bacterial response to these newer agents. Traditional approaches for predicting pathogen response to an antibiotic do not apply to combination therapy. We aimed to develop a modelling framework to predict treatment response based on resistome information, using isolates of the worldwide-disseminated high-risk clone sequence type (ST) 235 and β-lactam antibiotics as the example. In this hollow-fibre in-vitro infection study, we used three extensively drug-resistant ST235 clinical isolates from the national collection of the Clinical Microbiology Department of the Hospital Son Espases (Palma de Mallorca, Spain) that were hospital-acquired, were isolated following routine microbiological procedures from different patients between 2017 and 2022, were susceptible to ceftolozane-tazobactam, and had different levels of meropenem resistance. The selected isolates (ST235-05, ST235-09, and ST235-10) showed classical β-lactam resistance mechanisms pre-treatment. The isolates were investigated in 240-h dynamic hollow-fibre in-vitro infection models (HFIMs). The studies exposed the isolates to pharmacokinetic profiles of ceftolozane-tazobactam (simulating 1 g of ceftolozane and 0·5 g of tazobactam as a 3-h infusion every 8 h) and meropenem (simulating 6 g per day continuous infusion) as observed in hospitalised patients, as monotherapy and in combination. Treatment response was assessed through the quantification of the time-courses of viable total and resistant bacteria. Whole-genome sequencing identified the mechanisms of emerging resistance. A quantitative systems pharmacology (QSP) approach was used to model total and resistant bacterial counts and corresponding pharmacokinetic data from the HFIM. Monte Carlo simulations were used to predict treatment responses in 1000 virtual infected patients treated with ceftolozane-tazobactam and meropenem as monotherapies or in combination over 10 days. In the HFIMs, each antibiotic alone amplified resistance by approximately 48 h for all isolates; that is, monotherapies resulted in a higher concentration of resistant bacteria compared with the control treatment at the respective time, except ceftolozane-tazobactam against ST235-10. Combination of ceftolozane-tazobactam and meropenem was synergistic (bacterial counts ≥2 log10 colony forming units [CFU] per mL lower than the best performing monotherapy and initial inoculum) against all isolates and suppressed resistance. Against ST235-10, ceftolozane-tazobactam monotherapy reduced counts to less than 1 log10 CFU per mL from 192 h onwards, whereas the combination reached less than 1 log10 CFU per mL by 24 h. Across strains, population genomics confirmed monotherapy failures were associated with emerging resistance mechanisms (ceftolozane-tazobactam: ampC Ω-loop mutations; meropenem: ftsl mutation). The developed QSP model incorporated baseline resistance mechanisms and those emerging in resistant mutant subpopulations. The model explained and predicted the monotherapy failures involving amplification of these subpopulations, and synergistic killing and resistance suppression by the combination. Simulations using the model predicted bacterial regrowth above the initial inoculum for more than 90% of patients after 0 to approximately 3 days for meropenem monotherapy across all strains and for ceftolozane-tazobactam monotherapy against ST235-05 and ST235-09. For ceftolozane-tazobactam monotherapy against ST235-10, regrowth was predicted for approximately 30% of patients. In contrast, the simulations predicted sustained bacterial killing of at least 2 log10 CFU per mL compared with the initial inoculum by the combination for more than 89% of patients across all strains. To our knowledge, this model is the first to characterise and predict the time-course of responses of clinical isolates to antibiotics only by the resistance mechanisms present and their complex interplay, representing a step towards pathogen-specific, personalised medicine. Australian National Health and Medical Research Council.

Covering: up to December 2025The incorporation of distinctive structures such as uncommon functional groups, distinct molecular scaffolds, unusual modifications and other characteristic structural features can significantly enhance metabolic stability, bioactivity, and pharmacokinetic properties of drug molecules, offering ways to optimize the design and synthesis of novel bioactive molecules in synthetic biology. Streptomyces, a highly diverse and widespread bacterial genus, produces an extraordinary array of secondary metabolites, exhibiting remarkable structural variety. This structural ingenuity lies at the heart of functional innovation, establishing Streptomyces as a prolific source for drug discovery. The vast and diverse structural repertoire of these natural products offers valuable inspiration for novel structural designs in medicinal chemistry. Moreover, the vast array of natural enzymes provides a versatile toolkit for the site-specific modifications of complex scaffolds, facilitating the development of novel drug molecules that bypass the structural limitations of traditional chemical synthesis. This review highlights Streptomyces natural products with rare functional groups, unique scaffolds, and atypical modifications, examining the enzymatic mechanisms to link biosynthetic diversity with synthetic biology applications and efficient cell factory design.

Despite the extraordinary scientific success of vaccines, vaccination policy continues to struggle to sustain public trust, legitimacy, and consistent uptake in many contemporary societies. Policy responses to these challenges frequently prioritize communication strategies, behavioral interventions, or stronger implementation, implicitly treating vaccination as a primarily biomedical intervention whose effectiveness depends on evidence dissemination and administrative execution. This article argues that such approaches overlook a structural limitation within vaccinology itself: the lack of an explicit framework to address vaccination as a social process embedded in public life. We propose a tripartite model distinguishing basic vaccinology, programmatic vaccinology, and social vaccinology. Social vaccinology is defined as the domain concerned with individual and collective behaviors arising from the interaction between policy design, social influences, ethical considerations, institutional trust, and public discourse. Recognizing social vaccinology does not replace scientific evidence or programmatic delivery but complements them by clarifying the social conditions under which vaccination policies succeed or fail. By reframing vaccination as both a technical and a governance challenge, this article offers a conceptual framework to support more socially robust and sustainable vaccination policies.

Developing microwave-absorbing materials with wideband efficacy, low density, and minimal thickness remains a key challenge for electromagnetic interference shielding and stealth. This study unveils two ultralight aerogels prepared in parallel: a ZnO/ZnFe2O4/Fe3O4/RGO heterostructure and its MWCNT-reinforced counterpart (ZnO/ZnFe2O4/Fe3O4/RGO/MWCNT), the latter incorporating both GO and MWCNT simultaneously during synthesis. The optimized composite demonstrates extraordinary bandwidth performance, achieving a reflection loss (RL) below -10 dB across an exceptionally broad frequency range of 5.4 to 18 GHz, effectively covering 12.6 GHz of the measurable spectrum with matching thicknesses of just 1.4 to 4.0 mm. The formation of a synergistic conductive network between RGO and MWCNTs facilitates superior charge transport and dielectric loss, which is instrumental in realizing this ultra-wideband absorption. The central finding of this work is that the material's architecture successfully fulfills the dual criteria of excellent impedance matching and a high attenuation coefficient. The presented aerogel, with its remarkable bandwidth, represents a highly promising candidate for next-generation electromagnetic wave absorption applications.

Nonlocal metamaterials, which are metamaterials that interact with non-neighboring unit cells, have recently attracted growing attention as a new paradigm for wave control owing to their extraordinary band structures. However, existing nonlocal metamaterials remain limited in scalability, making it difficult to implement multiple nonlocal couplings and higher-dimensional arrays. Elastic nonlocal metamaterials have an additional limitation of mode coupling, which hinders clear investigations of unique nonlocal wave phenomena in individual elastic wave modes. This study addresses these limitations by proposing a new material platform for elastic nonlocal metamaterials, leveraging the "Metaspire" architecture with sequential rotation. Subsequently, the detailed wave motions around the maxon and roton are investigated, and the role of nonsymmorphic symmetry in flexural band behavior is further examined. In addition, actual fabrication and experimental validation are conducted to further support the proposed approach. The results quantitatively demonstrate the high scalability of the proposed method and its suppression of mode coupling. The proposed material platform provides a basis for the development of multifunctional wave platforms, thereby enabling various new-wave systems and devices.

The COVID-19 pandemic prompted extraordinary response measures in Central Asia (Kazakhstan, Kyrgyzstan, and Mongolia), but mortality outcomes varied. This retrospective population-based ecological study assessed age-standardized COVID-19 mortality rates (ASMRs per 100,000) from January 2020 to December 2021. Monthly COVID-19 deaths and population data by age and sex were obtained from official statistical and health sources. ASMRs were calculated using direct age standardization; monthly trends were examined by country, sex, and age group using joinpoint regression and interpreted in relation to governmental mitigation measures and circulating SARS-CoV-2 variants. Rates were higher in men than in women: in Kazakhstan, 24.8 vs. 12.8 in 2020 and 87.3 vs. 67.6 in 2021, in Kyrgyzstan, 46.6 vs. 25.2 and 40.8 vs. 29.7, respectively; and in Mongolia, 91.5 vs. 73.1 in 2021, with no deaths reported in 2020. In 2021, the gap between men and women narrowed as female ASMR increased fivefold. COVID-19 mortality was observed among infants in Kazakhstan and children ages 0-4 in Mongolia (2021). Rates rose sharply from age 60, especially among men and showed distinct country-specific timing: an early peak in Kyrgyzstan, delayed acceleration in Kazakhstan, and a late rise in Mongolia. These results underscore the need for timely, coordinated, age- and sex-sensitive response measures and targeted protection of vulnerable groups.

S-Adenosyl-L-methionine (SAM) is a central biological cofactor that supplied activated methyl groups and enables a broad-spectrum biochemical transformation. Beyond canonical SN2 methyl transfer, SAM-dependent enzymes could initiate radical-mediated chemistry via reductive SAM cleavage, enabling versatile reactions from methyl transfer to alkylation, isomerization, and decarboxylation. Despite their extraordinary catalytic plasticity and potential for sustainable industrial synthesis, SAM-dependent enzymes are often limited by insufficient activity, stability, and substrate scope, necessitating further engineering. In this review, we summarize SAM-dependent enzymes into methylation and nonmethylation catalytic systems, and systematically summarize recent protein engineering efforts aimed at enhancing activity, selectivity, and stability. Together, these advances establish a unified framework for unlocking the full catalytic potential of SAM-dependent enzymes, paving the way for their integration as versatile and sustainable biocatalysts in modern chemical synthesis.

Driven by the Confucian cultural ideal of "wang zi cheng long"-the fervent hope that one's child will rise like a dragon (i.e., achieve extraordinary success)-Chinese parents commonly engage in intensive academic involvement, such as frequent homework checking. However, the mechanisms through which this high-intensity monitoring affects adolescent mental health, and whether its effects are culturally specific, remain underexplored. Drawing upon the stimulus-organism-response (SOR) theory and the stress process model, this study used data from the 2022 China Family Panel Studies (CFPS) on 1831 adolescents aged 9-15 to examine the impact of parental homework checking frequency on adolescent loneliness, the mediating role of academic pressure, and the moderating role of parental educational expectations. The results show that parental homework checking frequency was positively associated with academic pressure, which in turn was positively associated with loneliness. The mediating role of academic pressure was significant. Parental educational expectations significantly and negatively moderated the relationship between homework checking and academic pressure, and the moderated mediation was significant. Simple slope analysis indicated that the positive association between homework checking and academic pressure was stronger. In the Confucian cultural context that emphasizes academic achievement and filial responsibility, frequent parental homework checking is associated with adolescent loneliness through increased academic pressure. Unexpectedly, high parental expectations served as a buffer-a pattern that differs from typical findings in Western individualistic cultures, where high expectations often directly increase psychological distress. These findings suggest that interventions in Chinese family education should distinguish controlling from supportive monitoring and transform high expectations into emotional support and resource investment, thereby reducing adolescents' academic pressure and loneliness.

Migrants rely on habitat shifts to adapt to changing environments, yet how migratory insect populations cope with global warming remains elusive. Here, we illustrated changes in heat tolerance, reproduction, flight performance, and energy metabolism pathways of a migratory insect Cnaphalocrocis medinalis, a serious pest of rice, induced by heat acclimation, which enhance the capacity to buffer further warming. Compared to natural populations, adults from the heat-acclimated strain exhibited longer heat knockdown time, higher critical thermal maxima, shorter pre-oviposition period, extended oviposition period, and increased fecundity under heat stress. Heat acclimation promoted the take-off behavior at an extremely high temperature and flight distance of adults at normal temperature, and induced a greater number of differentially expressed genes of larvae when exposed to high temperature, particularly genes associated with energy metabolisms. Gene sets related to glycolysis/gluconeogenesis, tricarboxylic acid cycle, oxidative phosphorylation, and pentose phosphate pathway were markedly upregulated in the heat-acclimated larvae. The insulin receptor gene of adults was downregulated in the heat-acclimated strain at normal temperature but significantly upregulated under heat stress which may be involved in energy regulation for migration, reproduction, and heat tolerance. Collectively, our findings demonstrate that migratory populations have an extraordinary capacity to buffer heat stress through energy metabolism-mediated acclimation driven by global warming.

A high-performance optical fiber surface plasmon resonance (SPR) biosensor for the determination of dopamine (DP) is reported based on gold nanocone arrays combined with gold nanoparticles (AuNPs). The sensor was fabricated via thermal nanoimprinting, gold sputtering, and single-stranded DNA-assisted AuNPs immobilization to form gap hotspots. Finite element simulation and experimental results verified strong electromagnetic field enhancement via extraordinary optical transmission and SPR-LSPR coupling. The sensor achieved a detection limit of 2.7 × 10-14 M for DA, with sensitivity and FOM improved by 37.4% and 54.2% relative to conventional gold film structures. It showed excellent selectivity and stability in serum, cerebrospinal fluid (CSF), and whole blood. This robust, scalable design provides a promising label-free platform for ultrasensitive DA detection in clinical point-of-care applications.

In the present study, a distinctive lineage of lymnaeid gastropods from the deep-water deposits of the Late Miocene Lake Pannon (Central Europe) is revised. The examined material includes specimens from museum collections as well as newly collected fossils from different parts of the Pannonian Basin System. During the past 150 years, at least 30 deep-water lymnaeid species assigned to ten genera have been described from the Lake Pannon deposits; however, our examination of more than 700 specimens shows that these records represent only 11 species belonging to five genera. Lectotypes are designated for four species for which earlier type designations were invalid. Species belonging to the Radix-Velutinopsis-Undulotheca-Provalenciennesia-Valenciennius lineage form one of the most extraordinary molluscan groups of Lake Pannon. Their interest lies in their distinctive shell morphology - large (sometimes exceeding 10 cm), wide, thin, cap-like shells with reduced coiling and undulated ribs - and their deep-water mode of life, supported by occurrences in drill cores and bathymetrically calibrated by seismic sections. This taxonomic revision enables the lineage to be applied in deep-water biostratigraphy of Lake Pannon sediments. Based on first appearance datums of key lineage species and associated taxa from other mollusc groups, four new lineage zones are proposed, integrated with the established deep-water mollusc biozonation. In contrast to the anagenetic evolutionary patterns typical of biostratigraphically important Lake Pannon bivalves, this gastropod lineage shows predominantly anacladogenetic speciation.

The transient time correlation function (TTCF) method has emerged as a powerful methodology for accurately probing systems at low shear rates. In the present study, TTCF was used to evaluate the shear rate dependence of the slip length in a high-slip system consisting of water confined between graphene walls at experimentally accessible shear rates, for which classical nonequilibrium molecular dynamics (NEMD) is unfeasible. The corresponding Navier friction coefficient was computed for all shear rates spanning six orders of magnitude and compared with the equilibrium limit. We report for the first time NEMD results obtained at experimentally accessible shear rates using the TTCF approach for a system that has attracted significant interest over the past decades. The slip length calculated with TTCF is in good agreement with previous equilibrium molecular dynamics simulations and experiments. Our aim here is to highlight the extraordinary power of TTCF, particularly for high-slip (low effective shear rate) systems, and to verify that equilibrium methods directly match NEMD measurements at experimentally accessible shear rates.

Constructing chiral organic long-persistent luminescence materials has garnered considerable attention owing to their extraordinary ultralong emission duration but has thus far achieved limited success. Herein, we present a straightforward approach to develop chiral chromophore engineered donor for exploring chiral exciplex system, which exhibits a blue circularly polarized exciplex emission peaked at ~ 440 nm, as well as an ultralong yellow organic long-persistent luminescence from the triplet emission of chiral chromophore with emission peak at 540 nm and ultralong duration of 90 minutes. Particularly, the exciplex system achieves mirror-symmetric chiroptical signal with the dissymmetry factor of 7.8×10-3. Theoretical and experimental analyses reveal that the phenomenon is attributed to the charge transfer process that facilitates exciplex formation, followed by effective energy transfer from the exciplex to the chiral chromophore. The developed exciplex enables the applications of multi-level information encryption and three-dimensional display objects. This work presents a significant insight into advancing organic chiral afterglow materials with ultralong duration, unlocking broad application potentials across various domains.

The recently synthesized monolayer MoSi2N4 (Y.-L. Hong, Z. Liu, L. Wang, T. Zhou, W. Ma, C. Xu, S. Feng, L. Chen, M.-L. Chen and D.-M. Sun, Chemical vapor deposition of layered two-dimensional MoSi2N4 materials, Science, 2020, 369(6504), 670-674.) boasts extraordinary environmental stability and superior comprehensive performance, offering exciting opportunities for the exploration of two-dimensional MX2Z4 materials. However, the low carrier mobility of α-MoSi2N4 significantly limits its practical applications in field-effect transistor (FET) devices. In this study, first-principles calculations were utilized to systematically investigate the structural stability, photoelectronic properties, tensile mechanical behavior, and carrier mobility of a novel family of β-SnA2N4 (A = Si, Ge) monolayers. Our findings reveal that these β-SnA2N4 monolayers demonstrate remarkable dynamic and thermal stability. Specifically, calculations based on the HSE06 functional reveal that the SnSi2N4 and SnGe2N4 monolayers are semiconductors with band gaps of 3.36 eV and 2.13 eV, respectively. Additionally, the SnA2N4 monolayers exhibit distinct mechanical anisotropy, characterized by high ideal tensile strengths and critical tensile strains exceeding 27%, indicating outstanding ductility. Importantly, the SnA2N4 monolayers display exceptional anisotropic in-plane charge transport, achieving electron mobility levels of up to 103 cm2 V-1 s-1, surpassing those of the α-phase MA2N4 (M = Mo, W; A = Si, Ge) monolayers. These novel ternary monolayer structures are expected to enrich the 2D MA2Z4 material family and emerge as promising candidates for FET applications.

Meiosis requires specialized mechanisms to coordinate chromosome pairing, recombination, and stepwise chromosome segregation. Central to these processes are cohesin complexes that incorporate meiosis-specific subunits, including SMC1β, REC8, RAD21L, and STAG3. Unlike canonical mitotic cohesin, these variants endow germ cells with distinct regulatory properties that ensure durable sister chromatid cohesion, promote homolog interactions, and establish the unique segregation patterns of meiosis I and II. Genetic and cytological studies have revealed that individual kleisin subunits perform non-redundant functions: REC8 provides the primary replication-coupled cohesion essential for chromosome axis integrity, whereas RAD21L supports homolog pairing and recombination through mechanisms linked to double-strand break formation. At centromeres, protected cohesin complexes cooperate with shugoshin-PP2A to preserve cohesion and define kinetochore orientation, thereby enabling reductional division. A remarkable feature of mammalian oocytes is the extraordinary longevity of meiotic cohesin, which must be maintained for years to decades without efficient turnover. Age-dependent deterioration of this cohesion machinery represents a major source of chromosome mis-segregation, contributing to infertility, miscarriage, and congenital aneuploidies. In this Review, we focus on the molecular composition, regulation, and functional specialization of meiosis-specific cohesins in mammalian germ cells. We integrate recent genetic, biochemical, and imaging studies to discuss how distinct cohesin complexes partition tasks during prophase, how cohesion is protected at centromeres, and how cohesin failure underlies reproductive aging and disease.

The naked mole-rat (Heterocephalus glaber) defies mammalian norms with lifelong fertility and postnatal oogenesis. Unlike most mammals, which experience reproductive senescence due to depletion of a finite ovarian follicle pool, naked mole-rat queens maintain fertility for their entire 30+-year lifespan through multiple mechanisms, including postnatal oogenesis, an exceptionally large ovarian reserve, and maintenance of primordial germ cells into adulthood. This review explores the unique reproductive biology of naked mole-rats within the context of their eusocial lifestyle, examining how social suppression of reproduction in subordinates, the role of very-high-molecular-weight hyaluronan (vHMW-HA) in cancer resistance and tissue maintenance, and the maintenance of germline stem cell populations contribute to their extraordinary reproductive longevity. We discuss the evolutionary advantages of eusociality, mechanisms of reproductive suppression and activation, and the potential of naked mole-rats as a research model for understanding ovarian aging and developing fertility-preserving therapies in humans.