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AlphaFold 3 (AF3), an artificial intelligence (AI)-based software for protein complex structure prediction, represents a significant advancement in structural biology. Its flexibility and enhanced scalability have unlocked new applications in various fields, specifically in plant science, including improving crop resilience and predicting the structures of plant-specific proteins involved in stress responses, signalling pathways, and immune responses. Comparisons with existing tools, such as ClusPro and AlphaPulldown, highlight AF3’s unique strengths in sequence-based interaction predictions and its greater adaptability to various biomolecular structures. However, limitations persist, including challenges in modelling large complexes, protein dynamics, and structures from underrepresented plant proteins with limited evolutionary data. Additionally, AF3 encounters difficulties in predicting mutation effects on protein interactions and DNA binding, which can be improved with molecular dynamics and experimental validation. This review presents an overview of AF3’s advancements, using examples in plant and fungal research, and comparisons with existing tools. It also discusses current limitations and offers perspectives on integrating molecular dynamics and experimental validation to enhance its capabilities.

The availability of corneal donor tissue is limited in most developing countries. This study evaluated whether patients with coexisting cataract and Fuchs’ dystrophy with corneal decompensation awaiting Descemet’s membrane endothelial keratoplasty (DMEK) benefited from phacoemulsification. This is a retrospective case–control study which included patients with Fuchs’ dystrophy and evidence of corneal decompensation awaiting DMEK. Best-corrected visual acuity (BCVA) and central corneal thickness (CCT) were documented at baseline (pre-cataract surgery in the case group, or at the time of transplantation registry in the control group), 1-month and pre-DMEK. A total of 16 phakic patients with visually significant cataracts had cataract surgery during the study period, and 15 pseudophakic patients were included as controls. There was no significant difference with regard to BCVA at baseline, 1-month or pre-DMEK between the case and control groups. Similarly, no significant difference in CCT was found at baseline, 1-month or pre-DMEK. In the case group, 4 patients with improved visual acuity post-cataract surgery chose to defer DMEK. After stratification, statistical analysis showed significantly better BCVA in the deferred group ( n  = 4) at 1-month post-cataract surgery, compared to the DMEK group ( n  = 12) (0.21 ± 0.21 vs. 0.86 ± 0.29 LogMAR, P  = 0.004). The other parameters, including baseline BCVA and CCT at any time point documented, were not statistically different. In conclusion, in patients with Fuchs’ dystrophy and decompensated corneas awaiting transplantation, phacoemulsification did not lead to significant increase of corneal thickness nor deterioration of visual acuity. A few patients achieved satisfactory vision after cataract surgery and deferred endothelial keratoplasty.

Background Diabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment. Case presentation A 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/μL before medication, which increased to 429.09/μL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves’ disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved. Conclusion In this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.

Aims/hypothesisIt has been proposed that the neuro-insular network enables rapid, synchronised insulin secretion. However, to date, acquiring the pancreatic tissue map to study the neural network remains a challenging task as there is a lack of feasible approaches for large-scale tissue analysis at the organ level. Here, we have developed 3-dimensional (3D) panoramic histology to characterise the pancreatic neuro-insular network in young mice.MethodsPancreases harvested from young wild-type B6 mice (3 and 8 weeks old) and db/db mice (3 weeks old; db/db vs db/+) were used to develop 3D panoramic histology. Transparent pancreases were prepared by optical clearing to enable deep-tissue, tile-scanning microscopy for qualitative and quantitative analyses of islets and the pancreatic tissue network in space.Results3D panoramic histology reveals the pancreatic neurovascular network and the coupling of ganglionic and islet populations via the network. This integration is identified in both 3- and 8-week-old mice, featuring the peri-arteriolar neuro-insular network and islet–ganglionic aggregation. In weaning hyperphagic db/db mice, the 3D image data identifies the associated increases in weight, adipose tissue attached to the pancreas, density of large islets (major axis > 150 μm) and pancreatic sympathetic innervation compared with db/+ mice.Conclusions/interpretationOur work provides insight into the neuro-insular integration at the organ level and demonstrates a new approach for investigating previously unknown details of the pancreatic tissue network in health and disease.

Background In a heterogeneous population of cells, individual cells can behave differently and respond variably to the environment. This cellular diversity can be assessed by measuring DNA methylation patterns. The loci with variable methylation patterns are informative of cellular heterogeneity and may serve as biomarkers of diseases and developmental progression. Cell-to-cell methylation heterogeneity can be evaluated through single-cell methylomes or computational techniques for pooled cells. However, the feasibility and performance of these approaches to precisely estimate methylation heterogeneity require further assessment. Results Here, we proposed model-based methods adopted from a mathematical framework originally from biodiversity, to estimate genome-wide DNA methylation heterogeneity. We evaluated the performance of our models and the existing methods with feature comparison, and tested on both synthetic datasets and real data. Overall, our methods have demonstrated advantages over others because of their better correlation with the actual heterogeneity. We also demonstrated that methylation heterogeneity offers an additional layer of biological information distinct from the conventional methylation level. In the case studies, we showed that distinct profiles of methylation heterogeneity in CG and non-CG methylation can predict the regulatory roles between genomic elements in Arabidopsis. This opens up a new direction for plant epigenomics. Finally, we demonstrated that our score might be able to identify loci in human cancer samples as putative biomarkers for early cancer detection. Conclusions We adopted the mathematical framework from biodiversity into three model-based methods for analyzing genome-wide DNA methylation heterogeneity to monitor cellular heterogeneity. Our methods, namely MeH, have been implemented, evaluated with existing methods, and are open to the research community.

Atopic dermatitis (AD) and asthma are key manifestations of the atopic march, characterized by a progressive development of allergic diseases from early skin inflammation to later respiratory involvement. Emerging evidence highlights the role of gut microbiota in modulating immune responses. However, the therapeutic potential of specific probiotic strains in preventing or mitigating the atopic march remains underexplored. This study aimed to evaluate the immunomodulatory and therapeutic effects of selected probiotic strains in a murine model of ovalbumin (OVA)-induced AD and asthma. Mice received oral administration of B. plebeiu, B. ovatus, F. duncaniae, F. taiwanense, and F. prausnitzii for four weeks before being exposed to OVA to induce AD and, later, asthma. Skin reactions were assessed after OVA application, and asthma was induced via aerosolized OVA. Afterward, blood and lung fluid samples were collected to evaluate immune markers such as total IgE, OVA-specific IgE, and IL-4. The results showed that B. plebeius improved skin histology in AD, while B. ovatus initially induced AD symptoms but later reduced them significantly between days 40 and 54. B. plebeius and B. ovatus reduced serum total IgE in asthma. B. plebeiu, B. ovatus, F. duncaniae, F. taiwanense, and F. prausnitzii significantly lowered OVA-IgE levels in serum and IL-4 levels in lung fluid (p < 0.05). These selected probiotic strains helped reduce allergic skin responses and, later, asthma by decreasing inflammation, particularly IL-4. These findings support the potential of these probiotics to prevent or mitigate the progression from AD to asthma and offer promising insight into targeted probiotic interventions for allergic diseases.

PurposeTo evaluate the 1-year progression of myopia and associated risk factors in second-grade primary school children.MethodsThe myopia investigation study in Taipei provided semiannual visual acuity testing and cycloplegic refraction for all second-grade primary school children (mean age: 7.49 years) in Taipei who provided parental consent. A questionnaire was distributed to the participants’ parents before the first and third examinations. We evaluated 1-year follow-up data for children noted to have myopia on the first examination. Multinomial logistic regression models were applied to assess risk factors associated with myopia progression. Myopia progression was categorised, based on the change in spherical equivalent (ΔSE) over 1 year, as slow (ΔSE>−0.5 dioptres (D)), moderate (−1.0 D<ΔSE≤−0.5 D) or fast (ΔSE≤−1.0 D). Of the 4214 myopic children, data were analysed for 3256 (77.3%) who completed the 1-year follow-up evaluation.ResultsThe baseline SE was −1.43±1.1 D. The average ΔSE was −0.42±0.85 D, with 46.96%, 28.50% and 24.54% of the study subjects showing slow, moderate and fast myopia progression, respectively. When compared with slow myopia progression, fast myopia progression was associated with a greater myopic SE at baseline (OR: 0.67, 95% CI: 0.61 to 0.72) and a shorter eye–object distance when doing near work (OR: 1.45, 95% CI: 1.18 to 1.78). More outdoor activity time and self-reported cycloplegic treatment were not associated with slow myopia progression.ConclusionsChildren with fast annual myopia progression were more myopic at baseline and had a shorter reading distance. Our study results highlight the importance of having children keep a proper reading distance.

Debates about prehistoric Amazonian subsistence, social organization, and landscape use have ranged from ethnographically based characterizations of relatively mobile foragers to archaeological evidence that suggests sedentary agriculturalists. Recently, great antiquity of settled agriculture and complex social organization has been asserted for portions of the northern Amazon. However, the role of theory and inferences drawn from habitat diversity have receded in these debates. This paper synthesizes the current literature regarding long-term evolutionary changes in Amazon Basin societies with an archaeological case study from mound-building sites of Guyana and ethnoarchaeological data from Venezuelan forager–gardeners to develop a hypothesis regarding the critical role of habitat, aquatic resources, and seasonality in the transition from intensified foraging to cultivation.

Ischemia/reperfusion （I/R） injury is the main cause of tissue damage and dysfunction. I/R injury is characterized by Ca2＋ overload and production of reactive oxygen species （ROS）, which play critical roles in the process of I/R injury to the brain, heart and kidney, but the underlying mechanisms are largely elusive. Recent evidence demonstrates that TRPM2, a Ca2＋-permeable cationic channel and ROS sensor, is involved in I/R injury, but whether TRPM2 plays a protective or detrimental role in this process remains controversial. In this review, we discuss the recent progress in understanding the role of TRPM2 in reperfusion process after brain, heart and kidney ischemia and the potential of targeting TRPM2 for the development of therapeutic drugs to treat I/R injury.