Rice false smut caused by Ustilaginoidea virens is a major fungal disease of rice in rice-growing regions throughout the world. However, the key genes and key metabolites related to U. virens resistance in rice remain unclear. Here, we used transcriptomics and metabolomics to determine the gene expression and metabolite accumulation changes in rice at 5, 7, and 9 d after inoculation with U. virens. By comparing the transcriptomes of IR27 (resistant cultivar) and 9311 (susceptible cultivar) spikelets, variable transcriptional responses under control and infection conditions were revealed. In total, 11,235 and 13,453 differentially expressed genes (DEGs) were identified in IR27 and 9311, respectively. The results of Kyoto Encyclopedia of Genes and Genomes and co‑expression analyses showed that the DEGs involved in flavonoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction responded to disease resistance. Several WRKY transcription factors were also differentially regulated in the resistant and susceptible cultivars. The metabolome analysis identified 343 and 303 differentially accumulated metabolites in IR27 and 9311, respectively, including salicylic acid, jasmonic acid, gibberellin, d-pantothenic acid, and p-coumaric acid. Many of these are primarily involved in plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways. Furthermore, the combined transcriptome and metabolome analysis revealed that plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis were significantly enriched in resistant rice varieties. Therefore, these results provide valuable information on the molecular mechanisms by which rice defends against U. virens infection, and they will facilitate the development of disease‑resistant rice cultivars.
Accounts of normative ethics that are based on the African conception of personhood tend to say that the goal of morality is to develop one's normative personhood (i.e., character), which is accomplished by exercising other-regarding virtues in the context of community. One argument in the African philosophical tradition that defends the permissibility of euthanasia appeals to this understanding of personhood. This argument suggests that developing a sufficient degree of personhood leads to a kind of achievement dignity that can be lost in the process of a bad death. As such, euthanasia is permissible in order to preserve achievement dignity. I argue that there are a number of problems with this argument, including that it cannot apply to those who fail to develop their personhood, that it is impossible to lose achievement dignity for non-moral reasons, and that the argument may prove too much in justifying involuntary euthanasia. An argument for the permissibility of euthanasia that appeals to the achievement dignity associated with African personhood cannot be successful. Furthermore, shifting the argument to an appeal to status dignity, which is grounded in personhood, is unlikely to completely rescue it.
Age-related eye diseases (AREDs), such as diabetic retinopathy (DR), cataract, glaucoma, age-related macular degeneration (AMD), presbyopia, and represent the primary sources of vision impairment globally. Numerous investigations have indicated that the onset and progression of these conditions are significantly linked to oxidative stress (OS) affecting the eye. The Keap1-Nrf2-ARE signaling pathway is a well-established mechanism that defends the body against OS and inflammation. This pathway is also implicated in the advancement of AREDs. However, the contribution of Nrf2 is likely to be disease-context dependent, and in multifactorial conditions such as glaucoma and dry eye disease, OS should be viewed as one interacting mechanism among several pathogenic processes rather than the sole or dominant driver. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) serves as a key modulator of numerous life processes, playing a critical role in antioxidant mechanisms, anti-inflammatory activities, antifibrotic responses, and cancer development. This review emphasizes the possible role of Nrf2 in the onset and progression of AREDs. Additionally, it explores various Nrf2 activators, encompassing noncoding RNAs and external substances, that regulate Nrf2 expression via distinct pathways within ocular disease models and eye cells, thereby safeguarding them from harmful alterations. However, most evidence supporting Nrf2-targeted interventions in age-related eye diseases remains preclinical, and important issues including disease-specific ocular delivery, target engagement in human tissues, long-term safety, and the potential risks of chronic Nrf2 activation must be addressed before clinical translation can be considered feasible. Consequently, Nrf2 may represent a significant target for the safeguarding of ocular cells against assorted stressors and the prevention of ocular ailments.
In response to the large number of people who use substances involved in the criminal legal system, various diversion programs have been introduced as an alternative to standard legal proceedings and sanctions. Drug courts operating at trial courts are perhaps the best known example, but other formats have emerged. Opt for Help and Hope is a prosecutor-led diversion program operating at six municipal courts in New Jersey. This study set out to evaluate the implementation of Opt for Help and Hope as a program operating in the novel context of municipal courts. This cross-sectional study drew on semi-structured interviews with participants in two stakeholder groups in the six participating NJ municipalities: (1) professional stakeholders (n = 41), consisting of prosecutors, municipal judges, peer specialist providers, and public defenders, and (2) defendants who had completed the Opt for Help and Hope program (n = 7). Analyses used a hybrid inductive-deductive approach to code and thematically analyze interview transcripts. All program sites followed key elements developed by New Jersey Office of the Attorney General, although some components of program design, such as division of responsibilities between the county and municipal prosecutors, differed to fit local contexts. There was a universally positive view of the program and its objectives across sites and professional stakeholder categories. Interviewees from four sites expressed satisfaction with the program's results, while the remaining two sites reported lower-than-expected numbers of participants and successful completers. Buy-in from implementing stakeholders and interest in participating among eligible defendants were seen as key factors for program success. Lessons during implementation included the need to ensure sufficient administrative capacity, to think through key parameters such as eligibility criteria and definition of compliance, and to pay attention to the potentially conflicting role and responsibilities of peer specialists working with program participants and reporting to the courts. Municipal courts offer a feasible diversion opportunity away from the criminal legal system. Ensuring adequate administrative capacity for program implementation, and sufficient education and support for service providers facing the problem of conflicting duties towards both participants and the court are key implementation considerations.
Cryo-electron tomography (Cryo-ET) has emerged as a transformative tool for visualizing viral components within their native cellular environment, enabling structural interrogation of viral life cycle events at nanometer resolution without chemical fixation or heavy metal staining. However, a persistent challenge in applying Cryo-ET to virus research is the unambiguous identification of specific viral components within densely crowded tomographic volumes. Electron density encodes mass and shape but not molecular identity, and as the cellular environment grows more complex, the assumption that a given density has no plausible alternative assignment becomes increasingly difficult to defend. This review surveys labeling and localization strategies for in situ Cryo-ET of viral components, encompassing label-free exploitation of native electron density, Cryo-immunogold labeling, genetically encoded and synthetic molecular tags, and correlative Cryo-light/electron microscopy (Cryo-CLEM) combined with Cryo-focused ion beam (Cryo-FIB) milling. We first summarize the landmark structural discoveries that in situ Cryo-ET has delivered across virus families, and then evaluate each labeling strategy against the structural and functional constraints that viral proteins impose, providing a practical framework for matching a labeling approach to a specific viral component and life-cycle stage.
Respiratory syncytial virus (RSV) impairs STAT3 activation in infected ciliated cells in infants, but not adults, causing apoptosis to facilitate virus spread. How age regulates the STAT3 response to RSV in human bronchial epithelial cells (BEpiCs) is unknown. Here, we identify an age-associated immune-poised physiological state in human bronchial basal stem cells (BSCs) and progeny BEpiCs, rendering robust RIG-I to guard against the inactivation of RIG-I-STAT3 signaling by RSV nonstructural protein 2. In contrast, infant BEpiCs are vulnerable to such inactivation by RSV due to lower RIG-I levels. We show that acute respiratory viral infection in specific pathogen-free mice, rather than physical age, triggers sustained epigenetic and transcriptomic remodeling in BEpiCs that resembles age-associated changes in human BEpiCs. In addition, cytokine pretreatment of human neonatal BSCs induces an adult-like immune-poised state that is maintained in progeny BEpiCs to defend against RSV. Therefore, respiratory infection and inflammation during a lifetime imparts the effect of age to BSCs, which fortifies RIG-I in progeny cells to mitigate RSV infection.
A widely cited 2024 analysis reported that only 5% of therapeutic interventions tested in animals obtain regulatory approval for human use, reviving the debate about the predictive value of animal models. This review asks how the scientific community has interpreted that finding and what collective position is emerging. The literature citing the original study was assembled from public citation indexes and classified by argumentative stance into five categories: defences of animal experimentation, critiques, methodological and disease-specific analyses, the author's own position, and work developing non-animal methods; no new animal data were generated. Across the corpus, attempts to strengthen the validity of animal studies tended to reduce rather than reinforce their apparent translational signal; the low translation rate recurred across unrelated disease domains; and even defenders of animal models increasingly restricted their claims to specific contexts while conceding poor translation. In parallel, non-animal methods-including organoids, organ-on-chip systems, and computational models-were repeatedly described as equalling or surpassing animal models in several fields. The scientific, ethical, economic and regulatory cases now converge, supporting a deliberately planned transition toward human-relevant methods rather than its deferral.
The prefrontal cortex (PFC) is often treated as the anatomical seat of executive control. We defend a distributed but structurally constrained account. The PFC is not an exclusive executive locus; it is a transient and structurally tuned cortical interface in which laminar differentiation, molecular tuning, recurrent synaptic persistence, thalamocortical embedding, and long-range connectivity converge to support context-sensitive control. We review prefrontal organization across genomic and transcriptomic patterning, receptor architecture, synaptic and interneuronal organization, laminar microcircuitry, white-matter constraints, and large-scale network dynamics. We argue that canonical cortical motifs are prefrontally parameterized toward four operations: convergence, filtering, maintenance, and feedback. Inputs are selected through molecularly tuned and inhibitory-gated laminar compartments; task-relevant states are stabilized through recurrent, neuromodulation-sensitive synaptic regimes; and selected states are exported through deep-layer corticocortical, corticostriatal, and corticothalamic channels. Evidence from gradual cortical damage, particularly low-grade glioma, suggests that preserved cognition after prefrontal injury is better explained by network-constrained functional reinstantiation than by strict regional essentialism. Yet compensation should not be equated with unconstrained migration of function; whether it depends on partial microcircuital convergence, synaptic re-weighting, network redistribution, or a combination of these mechanisms remains an open empirical question. Finally, we organize these mechanisms across encoding, maintenance/manipulation, and retrieval, arguing that prefrontal participation is temporally structured rather than statically localized. Progress will require a spatiotemporal multiscale atlas linking molecularly parameterized laminar motifs, tract engagement, and network interactions across cognitive stages.
Innate lymphoid cells (ILCs), a family of innate immune cells of lymphoid origin, serve as first responders to tissue damage and inflammation. They play a crucial role in defending mammals against tumor growth. ILCs can migrate between organs, move within tissues, and replenish from the blood during inflammation. Although much is known about ILCs in humans and mice, their properties in dogs are still largely unclear. To characterize canine ILCs, peripheral blood mononuclear cells (PBMCs) were isolated and cultured to expand ILCs. PBMCs were stimulated with recombinant human interleukin-2 (rhIL-2) and recombinant canine interleukin-7 (rcIL-7) for ILC1s expansion, rcIL-33 for ILC2s, or rh/rcIL-23 for ILC3s. Flow cytometry identified ILCs in PBMCs and cultures. We demonstrated that fresh PBMCs contained distinct populations of ILC1s, ILC2s, and ILC3s, characterized by the expression of cell surface markers (Lin-, CD45+, CD127+) and the subset-specific transcription factors T-bet+ (ILC1s), GATA-3+ (ILC2s), and RORγt+ (ILC3s). Following the expansion on days 0, 7, 14, and 21, the purity of each ILC subset increased, peaking on day 14. The expanded ILCs upregulated subset-specific transcription factors, indicating differentiation and enrichment. These findings provide a reliable method to isolate, characterize, and expand canine ILCs from blood, useful for research on their roles in health, disease, and potential therapies. They also offer insights into human cancer research, as dogs develop cancers similarly to humans.
Recent US policy decisions affecting domestic and global health funding have renewed debate on the United States' disproportionate influence over global health governance, institutions, and priorities. Although some scholars call for defending existing frameworks and others advocate reimagining global health beyond US-centric paradigms, these discussions often remain focused on immediate geopolitical developments. We place these debates in a broader historical context by examining Latin America, where US-led political and economic interventions interacted with domestic elites to shape health policy trajectories. Drawing on the traditions of Latin American social medicine and collective health, we analyze how global and national political-economic forces reshaped health systems in Chile and Brazil. Neoliberal reforms emerged through the convergence of international financial pressures, domestic elite coalitions, and policy diffusion. These reforms occurred through 3 interconnected processes: the depletion of public health capacity, the marketization and fragmentation of services, and the weakening of community-based care models. Latin America's experience demonstrates how neoliberal governance commodified health while also fostering enduring traditions of resistance and rights-based care, offering lessons for reimagining social medicine and global health today. (Am J Public Health. Published online ahead of print July 23, 2026:e1-e8. https://doi.org/10.2105/AJPH.2026.308564).
Advanced Persistent Threats (APTs) pose a serious threat to Internet of Things (IoT) systems because of their stealthiness, persistence, and ability to adapt to defensive responses. Communication-Based Train Control (CBTC) systems, as IoT-enabled railway signaling infrastructures, have evolved from relatively closed operational environments into interconnected cyber-physical networks, exposing train control systems to coupled cyber intrusion and operational-safety risks. To address this challenge, this paper proposes an alert-driven active defense framework for CBTC systems that integrates Bayesian belief updating, hypergame-based cognitive-bias modeling, and Hierarchical Reinforcement Learning (HRL). The framework converts intrusion detection system (IDS) alerts, network traffic observations, and cyber-physical observations into belief-state, transition, and reward inputs. The Bayesian model estimates attacker type and attack stage, the hypergame model represents deception-induced asymmetric cognition between attackers and defenders, and the HRL decouples strategic defense posture selection from tactical defense execution. The scenario-driven simulations in a CBTC APT defense setting show that the proposed model strategy achieves an 87.1% defense success rate against APT attacks while consuming 62.7% of the normalized defense resources, outperforming DQN, PG, and PPO under the same test conditions. These results suggest that explicitly coupling cyber observations, CBTC operational constraints, and hierarchical deception-aware policies can improve cost-aware active defense for railway signaling infrastructures.
Psychiatric illnesses and intellectual disabilities commonly occur in the criminal justice system and may impair an individual's ability to participate effectively in legal proceedings. Fitness to stand trial (FST) is an important safeguard for ensuring fair trial processes. This retrospective chart review examined the demographic, clinical, and legal profiles of 159 court-referred individuals assessed for FST at a major tertiary forensic psychiatry centre in New Delhi (India) between January 2017 and December 2022. Data on sociodemographic variables, ICD-10 diagnoses, current mental status, alleged offences, and FST outcomes were analysed using chi-square/Fisher's exact tests and multivariate logistic regression. The sample was predominantly male (81.1%) with a mean age of 37.9 years (SD 14.2). Psychotic disorders were the most frequent diagnosis (35.2%), followed by bipolar affective disorder and intellectual disability. Violent offences constituted 62.9% of alleged crimes. Overall, 54.7% were found fit to stand trial. Active psychiatric symptoms (adjusted OR 47.2, 95% CI 6.1-365.3) and organic mental disorder or intellectual disability (adjusted OR 22.5, 95% CI 4.8-105.6) independently predicted unfitness. Active psychopathology and cognitive impairment were the strongest determinants of unfitness, highlighting the need for structured assessment tools and restoration programmes under the Bharatiya Nagarik Suraksha Sanhita 2023.
Bullying represents a complex problem affecting students of all ages. Among the factors that influence it, appraisals of the transgressions and bystanders' responses play a very important role. The present study examined adults' emotional, evaluative, and behavioral responses to hypothetical bullying scenarios varying by bullying type and victim ethnicity. It also explored whether psychological distress was associated with bystanding behaviors as well as previous bullying experiences. The study used a mixed 3 × 4 vignette-based design. Victim ethnicity (i.e., Romanian, Roma, or Hungarian) was manipulated between participants, while bullying type was manipulated within participants through four scenarios describing physical, verbal, indirect, and cyberbullying. The final sample included 477 adults aged between 18 and 52 years. Participants appraised each transgression (i.e., empathic reactions, unacceptability), reported their likely bystander behavioral intentions (i.e., defend, ignore, report or join the aggression), completed the Depression Anxiety and Stress Scale (DASS-21) and reported previous bullying experiences as victim, witness, and aggressor. Bullying type was the most consistent factor shaping participants' appraisals as well as bystander reactions. The most tolerated forms were indirect bullying (e.g., highest probability to join the aggression) and verbal bullying (e.g., lowest unacceptability) the least accepted was physical bullying (e.g., lowest probability to join the aggression) while cyberbullying elicited specific patterns (i.e., lower empathy but higher willingness to report the incident). Victim ethnicity had a very limited effect, only concerning reporting intentions: lower for Hungarian targets compared to Romanian. Psychological distress was mainly associated with previous victimization and witnessing, while associations with scenario-based responses were smaller and more specific. The findings suggest that bystander responses are differentiated across bullying forms and prevention efforts should address subtle, indirect, verbal, and online forms of bullying, as these may be more easily normalized or less directly confronted.
This longitudinal study examined the extent to which students' outcome expectations (i.e., beliefs about the consequences of behaviors) and outcome values (i.e., the importance placed on these consequences) regarding defending behavior, as well as their individually and collectively perceived expectations from teachers and peers, and teachers' social management strategies, relate to students' behaviors in bullying situations. Participants included 605 South Korean elementary school students (Mage = 10.49; 50.41% male) and their teachers, assessed at the start and end of a five-month academic semester. Controlling for baseline behaviors, students who reported stronger outcome values and perceived greater expectations to defend at Wave 1 demonstrated lower levels of bullying, victimization, and bystanding, and higher levels of defending at Wave 2. Moreover, individual and collective perceived expectations, along with teachers' social management strategies, moderated these associations. Specifically, negative associations between outcome expectations and bullying or victimization emerged only when students perceived strong expectations from teachers and peers that they should defend. The positive association between outcome values and defending was evident only in classrooms where collective expectations for defending were high. In classrooms with high levels of teacher social management, bullying remained low regardless of students' outcome values, whereas associations between outcome values and bullying were evident primarily in classrooms with lower levels of teacher social management. These findings underscore the importance of perceived social norms and proactive teacher strategies in shaping students' behavioral responses to bullying.
HIV (Human Immunodeficiency Virus) is a virus that causes the immune system to be damaged, which results in reducing the body's ability to defend against infections and illnesses. This study aims to model new HIV cases among adults in KSA using selected growth, time series, and hybrid models. The study utilized official data on new HIV/AIDS cases among adults (15-49) from the World Bank website for the period 1990-2024. Various growth, conventional time series and hybrid models were proposed and used to model the series. The accuracy measures like RMSE, MAE, MAPE, MASE, and SMAPE were used to compare models, and the DM test was applied to assess the consistency between model predictions. Results were considered statistically significant if p < 0.05 and all the analyses and visualizations were performed in R-Studio. The time-series data of newly infected HIV cases among adults (ages 15-49) from 1990 to 2024 showed the mean number of cases was approximately 502 ± 323. Among the hybrid frameworks evaluated, Exponential-ETS emerged as the superior model, attaining the lowest RMSE value of 91.500, outperforming all competing specifications. The forecast for 2025 using the hybrid model projects new cases at 1,553.91 (95% CI: 1,272.23-1,828.94), rising to 2,157.74 (95% CI: 1,497.40-2,866.45) by 2029. However, the projected annual increment is lower than the surge observed in 2019-2024. This study concluded that the hybrid model provides the most robust forecasting framework for HIV incidence in KSA. The 5-year projections indicated a continued upward trend, but with a decelerated rate of growth compared to the sharp surge observed in 2019-2024. This deceleration suggests progress towards Vision 2030 goals of reducing the burden of infectious diseases through strengthened health infrastructure, expanded screening programs, and improved public health awareness.
We offer a practical roadmap for implementing Counsel at First Appearance (CAFA) in the United States using evidence from Texas. CAFA consists of early access to legal representation for individuals facing bail adjudications after arrest, a stage of the case in which defendants do not enjoy a federal constitutional right to counsel. Drawing on randomized studies conducted in Texas and observations from jurisdictions that adopted CAFA, the paper outlines a step-by-step approach to implementation. It identifies stakeholders, including judges, public defenders, prosecutors, court administrators, and policymakers-and emphasizes the importance of early coordination and shared objectives. Alongside procedural guidance, the paper presents a set of questions for jurisdictions to consider during planning and rollout. By providing actionable strategies, the paper serves as a resource for jurisdictions and policymakers aiming to enhance fairness and efficiency through CAFA.
This study aimed to quantify and compare the absolute daily and weekly external loads and training-to-match ratios of high-speed running distance (HSRD) and sprint distance (SPD) across the microcycle in semi-professional male soccer players. Twenty-four players from a Portuguese fourth-division team were monitored across nine standardized microcycles (7 days; 1 match) during the 2024-2025 competitive season using Global Navigation Satellite System devices. Absolute HSRD and SPD values were calculated for each training day and match, and daily and weekly training-to-match ratios were derived. Linear mixed-effects models assessed the effects of weekday, playing position, and their interaction. Match day elicited the highest absolute HSRD and SPD across all positions (p < 0.001). Within the training week, HSRD peaked on MD-3, whereas SPD peaked on MD-2, with the lowest values observed on MD-1. Significant position-by-day interactions were identified for both HSRD and SPD (p < 0.001). Wide defenders and midfielders accumulated greater absolute HSRD during both training and matches, while central defenders exhibited comparatively higher training-to-match ratios despite lower absolute match demands. Notably, in the analyzed team, all playing positions exceeded 100% of match-derived HSRD and SPD during the training week. In conclusion, the semi-professional soccer players investigated herein accumulated weekly high-speed and sprinting loads that exceeded match demands, although their distribution varied by playing position and training day. Confirmatory studies are necessary to further explore training-to-match load ratios across different competitive levels.
Cardiovascular disease (CVD) remains the leading cause of premature global mortality and one of the largest contributors to disability-adjusted life years lost. Over the past decade, the field has been transformed by the convergence of population biobanks, deep learning applied to imaging and electrocardiography, polygenic risk scores, wearable biosensors, and methodological advances in causal inference and target trial emulation. These innovations are reshaping precision public health for the general population. Yet the gains have not been equitably distributed. People with disability (PwD), comprising approximately 16 per cent of the global population and recognised by the United States National Institute on Minority Health and Health Disparities as a population experiencing health disparities are systematically under-represented in clinical trials, biobanks, electronic health records and the artificial-intelligence (AI) models trained upon them. Their cardiovascular health is therefore both worse and less precisely characterised than that of the general population. This article maps the key methodological vectors of change in CVD epidemiology, explains why each has so far failed to reach PwD, and presents a layered, defendable framework for disability-inclusive big-data and AI-enabled CVD research. It argues that disability inclusion is not a peripheral equity concern but a stress-test for the validity, generalisability and ethical legitimacy of the entire precision-cardiovascular enterprise.
It is well-established that teachers' perceptions of their students are impacted by their students' behavior, gender, and race. Less is known as to the impact of students' more nuanced behaviors such as defending victims of bullying. Participants included 1404 4th- and 5th-graders (19.0% Black girls, 20.9% Black boys, 30.0% White girls, 31.1% White boys). Peers rated children's defending in the fall. Teachers rated children's prosocial and aggressive behavior in the fall, winter, and spring. Linear growth curve models revealed that defending was associated with being perceived by the teacher as more prosocial and, particularly for Black children, less aggressive. However, high-defending Black children were viewed as increasingly aggressive if they had many same-race classmates. Furthermore, low-defending White girls were rated as similarly, or more, prosocial than high-defending boys. Thus, defending may contribute to teachers' positive impressions of their students but may not overcome potential racial and gender biases.