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The role of PD-1 signaling in health and immune-related diseases
Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.
Journal Article
Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis
High-throughput screening platform for the testing of small bioactive molecules that promote oligodendrocyte differentiation and remyelination: a new path to the discovery of potential drugs for multiple sclerosis.
Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.
Journal Article
العمارة الصينية : بناء الجمال بالطوب والحجارة : السحر الأزلي
فن العمارة الصينية قديمة العهد كالحضارة الصينية. من كل مصدر للمعلومات الأدبية والرسمية والمثالية، هناك أدلة قوية تدل على أن الصينيين كانوا يتمتعون دائما بنظام بناء السكان الأصليين الذي احتفظ بخصائصه الرئيسية من عصور ما قبل التاريخ حتى يومنا هذا. على مساحة واسعة من تركستان الصينية إلى اليابان، من منشوريا إلى النصف الشمالي من الهند الصينية الفرنسية، نفس نظام البناء هو السائد. هذا هو مجال التأثير الثقافي الصيني. أن هذا النظام من البناء يمكن أن يظل موجودا لأكثر من أربعة آلاف سنة على مثل هذا الإقليم الشاسع ولاتزال البنية الحية، محافظة على خصائصها الرئيسية على الرغم من الغزوات الأجنبية المتكررة العسكرية والعقلية والروحية، هي ظاهرة قابلة للمقارنة فقط لاستمرارية الحضارة التي تشكل جزءا لا يتجزأ منها.»ليانغ، سو-شونغ، 1984، 1984 خلال القرن العشرين حاول المهندسون المعماريون الصينيون المدربون من الغرب الجمع بين التصاميم الصينية التقليدية في الهندسة المعمارية الحديثة (عادة الحكومة) مع نجاح كبير علاوة على ذلك فإن الضغط من أجل التنمية الحضرية في جميع أنحاء الصين المعاصرة يتطلب سرعة أعلى من البناء ونسبة مساحة الطابق الأعلى، مما يعني أنه في المدن الكبرى الطلب على المباني الصينية التقليدية، والتي هي عادة أقل من 3 مستويات ورفض لصالح العمارة الحديثة. مع ذلك، فإن المهارات التقليدية للهندسة المعمارية الصينية، بما في ذلك النجارة الرئيسية والثانوية والبناء والحجارة لا تزال تطبق على بناء العمارة العامية في المنطقة الريفية الشاسعة في الصين.
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Dual-band transmission polarization converter based on planar-dipole pair frequency selective surface
A novel linear polarization converter operating in C- and X-bands with high polarization conversion ratio is described and demonstrated based on frequency selective surface. The building element is a planar-dipole pair, which is orthogonally printed on a double-layer substrate and vertically connected by a pair of through-via holes functioning as a quasi-two-wire transmission line coupler. A perforated metal shielding layer is sandwiched between the double-layer structure to only support a transverse electric and magnetic (TEM) mode coupling between the top and bottom dipolar components. The front dipole responds to the incident transverse electric (TE) wave, and sends the induced current into the two-wire transmission line to feed the bottom dipole. The bottom dipole is orthogonal or oriented at an arbitrary angle with respect to the top one, and a resultant outgoing transverse magnetic (TM) wave or arbitrary orientation polarized wave can be achieved. In addition, a bidirectional orthogonal polarization converter is realized by using double orthogonally arranged planar-dipole pairs, which are also printed on the same double-layer substrate.
Journal Article
Twenty-Five Years of Evolution and Hurdles in Electronic Health Records and Interoperability in Medical Research: Comprehensive Review
Electronic health records (EHRs) facilitate the accessibility and sharing of patient data among various health care providers, contributing to more coordinated and efficient care.
This study aimed to summarize the evolution of secondary use of EHRs and their interoperability in medical research over the past 25 years.
We conducted an extensive literature search in the PubMed, Scopus, and Web of Science databases using the keywords Electronic health record and Electronic medical record in the title or abstract and Medical research in all fields from 2000 to 2024. Specific terms were applied to different time periods.
The review yielded 2212 studies, all of which were then screened and processed in a structured manner. Of these 2212 studies, 2102 (93.03%) were included in the review analysis, of which 1079 (51.33%) studies were from 2000 to 2009, 582 (27.69%) were from 2010 to 2019, 251 (11.94%) were from 2020 to 2023, and 190 (9.04%) were from 2024.
The evolution of EHRs marks an important milestone in health care's journey toward integrating technology and medicine. From early documentation practices to the sophisticated use of artificial intelligence and big data analytics today, EHRs have become central to improving patient care, enhancing public health surveillance, and advancing medical research.
Journal Article
Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis
Grafting of C7 from the nonparalyzed to the paralyzed side in patients with arm paralysis resulted in greater improvements in power, spasticity, and function at 12 months than rehabilitation therapy alone, and functional connection to the ipsilateral cerebral hemisphere developed.
Journal Article
Glaucoma, Alzheimer's Disease, and Parkinson's Disease: An 8-Year Population-Based Follow-Up Study
Glaucoma is the leading cause of irreversible blindness worldwide and primary open-angle glaucoma (POAG) is the most common type of glaucoma. An association between POAG and the subsequent risk of Alzheimer's disease (AD) and Parkinson's disease (PD) was unclear.
To investigate the association between POAG (including normal-tension glaucoma) and the subsequent risk of AD or PD 8 years following a diagnosis of POAG.
We performed a retrospective, propensity-score-matched analysis of a population-based cohort consisting of patients with and without POAG aged 60 years and older. Control patients without POAG were propensity-score matched to POAG patients based on their baseline characteristics.
The incidence rates and confidence intervals (CIs) of AD among the patients with and without POAG were 2.85 (95% CI: 2.19-3.70) and 1.98 (95% CI: 1.68-2.31) per 1000 person-years, respectively. The incidence rates of PD among the POAG and non-POAG cohorts were 4.36 (95% CI: 3.52-5.39) and 4.37 (95% CI: 3.92-4.86) per 1000 person-years, respectively. Kaplan-Meier failure curves showed that the POAG patients had a higher risk of AD than the control patients did (log-rank test, P= .0189). However, the cumulative PD hazard ratios for the POAG and non-POAG patients did not differ significantly (log-rank test, P= .9953).
In elderly patients, POAG is a significant predictor of AD, but POAG is not a predictor of PD.
Journal Article