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أليس في بلاد العجائب
تبدأ القصة في حديقة البيت كانت أليس مع أختها الكبرى حيث كانت تخبرها عن العالم من كتاب التاريخ لكن اليس لم تكن تصغي لها لأن هذا الكتاب لم يكن يحتوي على صور ونقاش فأصبحت تفكر في عالمها الخاص بها حيث تغني الأزهار وترقص العصافير فيظهر أرنب من العدم وكان مستعجلا مع ساعة جيب وفضولها جعلها تلحق الأرنب لترى لم هو مستعجل فلحقت به حتى وصولها إلى جحر صغير لا يمكنها دخوله حتى يدلها الأرنب على قنينة صغيرة يجعل الجميع يتقلص ويصبح صغيرا جدا فتمكنها من الدخول لتقع في الجحر المعتم وتمشي في الممر المظلم حتى تصل إلى غابة فيظهر لها أخوان توأمان ويبدأ كل منهما بقص القصص عليها ولكن أليس قامت بتجاهلهما وهربت مشيا في الغابة الكبيرة حين سمعت أصوات غناء ورقص فتبعت الصوت حتى وصلت إلى بيت المجنون حيث كانت حفلة شاي.
BOOK
Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells
The genome is organized within the nucleus as three-dimensional domains that modulate DNA-templated processes. Bintu et al. used high-throughput Oligopaint labeling and imaging to observe chromatin dynamics inside the nuclei of several different mammalian cell lines. After combining the datasets, single-cell matrices revealed chromatin arranged in topologically associating domains (TADs). Removing cohesin resulted in a loss of aggregate TADs among populations of cells, but specific TADs were still detected at the single-cell level. Furthermore, higher-order organization was detected, suggestive of cooperative interactions within the genome. Science , this issue p. eaau1783 Chromatin imaging reveals topologically associating domain–like structures with spatially segregated conformations. The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method for tracing chromatin organization with kilobase- and nanometer-scale resolution, unveiling chromatin conformation across topologically associating domains (TADs) in thousands of individual cells. Our imaging data revealed TAD-like structures with globular conformation and sharp domain boundaries in single cells. The boundaries varied from cell to cell, occurring with nonzero probabilities at all genomic positions but preferentially at CCCTC-binding factor (CTCF)- and cohesin-binding sites. Notably, cohesin depletion, which abolished TADs at the population-average level, did not diminish TAD-like structures in single cells but eliminated preferential domain boundary positions. Moreover, we observed widespread, cooperative, multiway chromatin interactions, which remained after cohesin depletion. These results provide critical insight into the mechanisms underlying chromatin domain and hub formation.
Journal Article
Spatial organization of chromatin domains and compartments in single chromosomes
The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.
Journal Article
A Fully Automated Deep Learning Pipeline for Anatomical Landmark Localization on Three-Dimensional Pelvic Surface Scans
Accurate identification of anatomical landmarks on three-dimensional (3D) pelvic surface scans is essential for musculoskeletal assessment, yet manual procedures remain limited by operator dependence and soft tissue variability. This study presents a fully automated deep learning pipeline for localizing anatomical landmarks on the posterior pelvic region from raw 3D point cloud data. The pipeline integrates three modules: PelvicROINet for extracting the region of interest, PelvicAlignNet for rotation correction to standardize posture, and PelvicLandmarkNet for localizing six anatomical landmarks including the bilateral posterior superior iliac spines, bilateral iliac crests, L1, and L4. The models were trained independently with task-specific annotations and combined sequentially during inference. Under a subject-level split evaluation setting, the fully integrated system achieved a median error of 11.25 mm, demonstrating consistent localization performance across unseen subjects. Compared with manual landmark marking, the automated measurements showed improved within-visit repeatability, with reduced variability and higher intraclass correlation coefficients. The entire inference process required approximately three seconds per scan, supporting near real-time clinical applicability. These results indicate that the proposed modular framework enhances numerical consistency and robustness in surface-based pelvic landmark assessment and provides a scalable foundation for AI-assisted musculoskeletal evaluation and longitudinal monitoring.
Journal Article
Coronavirus vaccine development: from SARS and MERS to COVID-19
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.
Journal Article
Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications
Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.
Journal Article
COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection
Coronavirus Disease 2019 (COVID-19) has been the most severe public health challenge in this century. Two years after its emergence, the rapid development and deployment of effective COVID-19 vaccines have successfully controlled this pandemic and greatly reduced the risk of severe illness and death associated with COVID-19. However, due to its ability to rapidly evolve, the SARS-CoV-2 virus may never be eradicated, and there are many important new topics to work on if we need to live with this virus for a long time. To this end, we hope to provide essential knowledge for researchers who work on the improvement of future COVID-19 vaccines. In this review, we provided an up-to-date summary for current COVID-19 vaccines, discussed the biological basis and clinical impact of SARS-CoV-2 variants and subvariants, and analyzed the effectiveness of various vaccine booster regimens against different SARS-CoV-2 strains. Additionally, we reviewed potential mechanisms of vaccine-induced severe adverse events, summarized current studies regarding immune correlates of protection, and finally, discussed the development of next-generation vaccines.
Journal Article
Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant
Background
Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients.
Methods
We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled.
Results
Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9–20) and 11 (range, 8–19) days, with a cumulative incidence of 97.8 and 97.1% (
P
= 0.528), respectively. HID recipients had an increased cumulative incidence of grades II–IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%,
P
< 0.001), grades III–IV aGVHD (10.1 vs. 1.5%,
P
= 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%,
P
< 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%,
P
= 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (
P
= 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (
P
= 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type.
Conclusions
Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.
Journal Article
Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms
ObjectiveThe SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.DesignCOVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.ResultsAmong enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2.ConclusionWe report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
Journal Article
Programmable motion of DNA origami mechanisms
DNA origami enables the precise fabrication of nanoscale geometries. We demonstrate an approach to engineer complex and reversible motion of nanoscale DNA origami machine elements. We first design, fabricate, and characterize the mechanical behavior of flexible DNA origami rotational and linear joints that integrate stiff double-stranded DNA components and flexible single-stranded DNA components to constrain motion along a single degree of freedom and demonstrate the ability to tune the flexibility and range of motion. Multiple joints with simple 1D motion were then integrated into higher order mechanisms. One mechanism is a crank–slider that couples rotational and linear motion, and the other is a Bennett linkage that moves between a compacted bundle and an expanded frame configuration with a constrained 3D motion path. Finally, we demonstrate distributed actuation of the linkage using DNA input strands to achieve reversible conformational changes of the entire structure on ∼minute timescales. Our results demonstrate programmable motion of 2D and 3D DNA origami mechanisms constructed following a macroscopic machine design approach.
Journal Article