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الطيور البنية المهاجرة : قصص
يولي الكاتب في هذه المجموعة القصصية اهتماما خاصا بالزمن، وارتباطه بالإنسان ذاته دون تجريد، وبعده المكاني وذاكرته، ويوحي بأن الكتابة تجل للزمن الإبداعي، حيث يقول : «غالبا ما نتحدث عن الأبعاد المكانية الثلاثة، إضافة إلى بعد زمني واحد، إذن هي أربعة أبعاد، والبعد الأرجح الذي يمنحنا مغزى هو البعد الزمني، ولا أعني بذلك أن البعد المكاني لا أهمية له».
BOOK
Study of Retinoic Acid-Induced Osteoarthritis: Integrating RNA-Sequencing, Network Pharmacology, Molecular Docking, and Experimental Validation
Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and disruption of chondrocyte homeostasis. Although retinoic acid (RA) has been used in OA models, its precise targets are not clear. A translational framework was employed, integrating RNA-sequencing results, network pharmacology prediction, computational ligand-receptor molecular docking, and biological experimental validation, to systematically elucidate RA’s disease-modifying targets in OA pathogenesis. RNA-sequencing of RA-treated chondrocytes revealed 656 differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment [Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)] highlighted key pathways, including extracellular matrix (ECM) reorganization and PI3K-Akt-mediated mechanotransduction and others. Network pharmacology analysis identified 42 shared targets between RA and OA. PPI analysis and functional enrichment (GO/KEGG) highlighted pathways including the renin–angiotensin system and the neuroactive ligand–receptor interaction, among others. Molecular docking ranked candidate targets by binding affinity of RA in descending order as MAPK14 (p38α), PTGER3 (PGE2 receptor), CA2 (CA2), and others. Five intersecting targets CA2, ACE, PTGS1 (COX-1), PGR, and EDNRA (ETAR) were identified by integrating RNA-sequencing (RNA-seq) results and network pharmacology predictions. These interactions were experimentally validated via western blot, RT-qPCR and immunofluorescence. RA increased the expression of MMP13, CA2 and ACE, and decreased the expression of COL2A1 in chondrocytes. siRNA-mediated knockdown of both CA2 (human CA2 homolog) and ACE (human ACE homolog) inhibit cartilage degradation through downregulating MMP13 and upregulating COL2A1. This study not only elucidates potential molecular mechanisms by which RA modulates chondrocyte catabolism but also offers a valuable reference for the development of novel OA therapeutics.
Journal Article
Burdens of sense organ diseases across global, regional, and national levels from 1990 to 2021 and projections for 2050
Background
Sensory organ diseases (SOD) pose a considerable challenge to global health. This study analyzed the burden of SOD from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021.
Methods
We analyzed prevalence, disability-adjusted life years (DALYs), and age-standardized rates using Joinpoint regression and age-period-cohort (APC) models to separate the effects of age, period, and birth cohort. Health inequalities were evaluated through the slope index of inequality (SII) and concentration index (CI). Additionally, we identified risk factors influencing DALYs and projected future disease burden trends for 2022 to 2051 using Bayesian age-period-cohort (BAPC) models.
Results
In 2021, the global prevalent cases of SOD reached 2,386,160,888 (95% uncertainty interval [UI]: 2,207,871,226 to 2,591,000,614), with 77,327,293 DALYs cases (95% UI: 53,419,192 to 107,972,583). Age-related hearing loss was the most common condition, accounting for 1,545,690,283 prevalent cases (95% UI: 1,480,358,023 to 1,618,714,974) and 44,449,944 DALYs cases (95% UI: 30,689,648 to 62,029,878). The highest age-standardized prevalence rates (ASPR) for blindness and vision loss were observed in Southern Sub-Saharan Africa and South Asia. DALYs attributable to high fasting plasma glucose and high body mass index (BMI) increased significantly from 903,991 to 97,878 in 1990 to 1,555,976 and 229,558 in 2021, respectively. Health inequality analysis revealed a reduction in both SII and CI for SOD from 1990 to 2021, indicating an improvement in health inequality. Future projections indicate that from 2022 to 2051, ASPR for SOD will continue to increase, with the ASPR of blindness and vision loss increasing by about 17.78%. While age-standardized DALYs rates (ASDR) are expected to stabilize, with the ASDR of age-related and other hearing losses is expected to rise by approximately 0.67%.
Conclusion
The burden of SOD is high and unevenly distributed. Increasing prevalence and DALYs highlight the need for targeted interventions. Future efforts should focus on risk mitigation and reducing health inequalities.
Journal Article
Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights
Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O
6
-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective autophagy, an immunosuppressive tumor microenvironment (TME), altered signaling pathways, and active drug efflux transporters. Recent advancements to overcome these resistance mechanisms, including enhancing TMZ bioavailability through nanoparticle-based delivery systems and the inhibition of efflux transporters, have been explored. Novel therapeutic approaches that target DNA repair pathways and manipulate autophagy are highlighted. Immunotherapeutic interventions reversing immune suppression and metabolic strategies targeting tumor metabolism offer additional avenues. Emerging therapies such as CRISPR-based gene editing, phytochemical combinations, repurposed drugs, and novel TMZ analogs designed to bypass MGMT-mediated resistance are also discussed. This review highlights current developments and identifies emerging areas, with the goals of enhancing clinical outcomes and prolonging survival for glioma patients.
Journal Article
The glymphatic system in neurodegenerative diseases and brain tumors: mechanistic insights, biomarker advances, and therapeutic opportunities
Dysfunction of the glymphatic system (GS), a brain-wide waste clearance pathway dependent on polarized aquaporin-4 (AQP4) water channels on astrocytic endfeet, is increasingly recognized as a critical mechanism in both neurodegenerative diseases and brain tumors. In Alzheimer’s (AD) and Parkinson’s (PD) diseases, impaired glymphatic function leads to the accumulation of neurotoxic proteins, including amyloid-β (Aβ), tau, and α-synuclein (α-syn). Contributing factors include loss of AQP4 polarization, reduced arterial pulsatility, genetic risks (e.g.,
APOE4
,
FAM171A2
mutations), and sleep disturbances. These functional impairments can be quantified using neuroimaging biomarkers such as the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus volume (CPV), which correlate with pathological burden and clinical decline, though the direct physiological interpretation of these metrics requires further validation. Conversely, in glioblastoma and other brain tumors, mechanical compression and lactate-driven acidosis obstruct perivascular fluid transport, promoting an immunosuppressive tumor microenvironment that limits T-cell infiltration and confers therapeutic resistance. Here, too, glymphatic dysfunction is reflected by a reduced ALPS index, which correlates with tumor grade, peritumoral edema, and survival. Emerging therapeutic strategies aimed at restoring GS function include pharmacological interventions (e.g., circadian regulators, AQP4 modulators), non-invasive techniques (e.g., cervical lymphatic stimulation, gamma stimulation, exercise), and surgical approaches (e.g., lymphatic-venous anastomosis). Advances in multimodal MRI and artificial intelligence (AI)-enhanced analytics further support novel diagnostic capabilities. This review highlights the dual role of the GS across neurological disorders and underscores its potential as a therapeutic target for enhancing waste clearance and immune modulation. However, significant challenges remain, including the validation of human biomarkers, elucidating bidirectional tumor–glymphatic crosstalk, and translating preclinical discoveries into clinical practice.
Journal Article
Influence of La2O3 Addition on Microstructure and Mechanical Properties of Al2O3 Ceramics
In this paper, alumina ceramics were prepared with alumina powder and lanthanum nitrate. The influence of La2O3 on the microstructure and properties of alumina ceramics were studied. The result showed that the addition of La2O3 contributed to the mechanical property of the samples. The alumina ceramics with adding of 0.05wt% La2O3 sintered at 1490°C had the best mechanical properties. And the flexural strength, fracture toughness of the ceramics could reach 571.902MPa and 5.82MPa•m1/2，which were improved by 37.55% and 10.65% respectively compared with the alumina ceramics without La2O3. Besides, the average grain size of alumina ceramic is about 2.8μm, and the effect of inhibition on grain growth of alumina ceramics was obvious.
Journal Article
Quality of plant-based diets in relation to all-cause and cardiovascular disease mortality in US adults with sarcopenia: a population-based study
Purpose
This observational study aimed to examine the relationship between three plant-based diet (PBD) indices and the risk of all-cause and cardiovascular disease (CVD) mortality in patients with sarcopenia.
Methods
Adults with sarcopenia from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey were included. A total plant-based diet index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI) were created based on 17 food groups and were assessed for their associations with all-cause and CVD mortality risk using Cox proportional hazards regression models, restricted cubic spine analysis, and interaction analysis.
Results
A total of 684 (222 from CVD) deaths were documented in 2218 participants (mean age 51.36 years; 53.90% men) during a median follow-up of 117 months. Compared with the lowest quartile, the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality in the highest quartile were 0.49 (0.33–0.75) for total PDI, 0.27 (0.19–0.39) for hPDI, and 1.85 (1.30–2.65) for uPDI. Similarly, for CVD mortality, the HRs and 95% CIs in the highest quartile were 0.29 (0.12–0.69) for total PDI, 0.30 (0.18–0.50) for hPDI, and 2.65 (1.21–5.77) for uPDI, compared to the lowest quartile. The protective associations of hPDI with all-cause and CVD mortality were more pronounced in participants younger than 45 years.
Conclusion
Higher adherence to PDI and hPDI is associated with a lower risk of all-cause and CVD mortality, whereas higher adherence to uPDI is linked to an increased risk of mortality in US adults with sarcopenia.
Journal Article
Treatment of acetabular fracture involving anterior and posterior columns using a single pararectus approach: surgical experience and preliminary results
Purpose
This study aims to evaluate the efficacy of single pararectus approach in patients confirmed with acetabular fracture involving anterior and posterior columns.
Methods
A total of 58 patients confirmed with acetabular fracture involving anterior and posterior columns and treated at our hospital between January 2015 and January 2020 were retrospectively analyzed. A single pararectus approach was applied for all patients. Routine X-rays were performed at follow-up of one, three, six, 12, and 18 months, and three-dimensional CT scans were added at six and 18 months. Fracture reduction quality was assessed using the Matta score system, and functional assessment used the Modified Merle D’Aubigné and Postel score system. Post-operative complications, including fat liquefaction and deep vein thrombosis, were recorded and analyzed.
Results
The median operation time was 186 min while the intra-operative blood loss was 421 mL. The rate of good-to-excellent reduction was 94.8%, and the rate of good-to-excellent hip function score reached 93.1%. Seven patients presented with post-operative complications, including three intra-operative small vascular injuries, two peritoneal small perforations, one fat liquefaction, and one deep vein thrombosis.
Conclusion
Using a single pararectus approach is convenient and effective for treating acetabular fracture involving anterior and posterior columns, especially those involving the quadrilateral area.
Trial registration
ChiCTR, ChiCTR2100054604. Registered 21 December 2022. Retrospectively registered,
http://www.chictr.org.cn/showproj.aspx?proj=144783
.
Journal Article
Integration of Network Pharmacology, Molecular Docking, and Experimental Validation to Identify the Effect of EGCG on Alleviating Chondrocyte Inflammatory Damage by Targeting ER Stress-STAT3 Crosstalk
Osteoarthritis (OA) is the most common joint disorder and a major global health burden. Epigallocatechin-3-gallate (EGCG), a green tea-extracted polyphenol, shows therapeutic potential for OA, but a comprehensive understanding of its mechanisms is essential to enhance clinical utility.
EGCG-related targets were identified utilizing the TCMSP, BATMAN-TCM, PharmMapper, and SwissTargetPrediction databases. OA-related targets were retrieved from GeneCards, DisGeNET, OMIM, and TTD databases. A protein-protein interaction (PPI) network was constructed using Cytoscape 3.10.1, and the CytoNCA plugin was used for topological analysis to identify the core targets. To clarify EGCG's therapeutic mechanisms in OA, we performed systematic functional annotation via Gene Ontology (GO) enrichment and interrogated relevant biological pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Furthermore, molecular docking was applied to assess the binding affinity between EGCG and key targets. Finally, in vitro experiments using primary chondrocytes stimulated with IL-1β were conducted to validate the predictions from network pharmacology.
488 EGCG-related targets were identified, with 172 overlapping OA-related genes. Four core genes were identified, including STAT3, TP53, AKT1, and JUN. GO enrichment analysis revealed 2163 biological processes, 92 cellular components, and 223 molecular functions; KEGG analysis identified 175 enriched signaling pathways. Molecular docking showed EGCG's binding affinity to core target STAT3 was approximately -8.1 kcal/mol. In vitro experiments showed that EGCG reduced IL-1β-induced catabolic and inflammatory responses in chondrocytes, which is linked with attenuated endoplasmic reticulum (ER) stress. Moreover, the involvement of STAT3 in the effects of EGCG that alleviate ER stress in OA has been established, highlighting its therapeutic potential.
This study reveals that EGCG may ameliorate the metabolic imbalance of extracellular matrix (ECM) and inflammatory responses by modulating the activity of the ER stress-STAT3 crosstalk.
Journal Article
MULTIFREQUENCY MONOPOLE ANTENNAS BY LOADING METAMATERIAL TRANSMISSION LINES WITH DUAL-SHUNT BRANCH CIRCUIT
The theory and design of a new family of multifrequency monopole antennas by smartly loading a set of complementary metamaterial transmission line (CMTL) unit cells are investigated. The distributed CMTL elements, epsilon negative (ENG) or double negative (DNG) through incorporating additional capacitive gaps, contain a Koch-shaped extended complementary single split ring resonator pair (K-ECSSRRP) etched on the signal strip. The K-ECSSRRP features dual-shunt branches in the equivalent circuit model, rendering a distinguished resonator with dual zeroth-order resonant (ZOR) modes. By smartly controlling the element layout and loading different numbers of unit cells, ten antennas covering different communication standards (GSM1800, UMTS, Bluetooth, DMB and WIMAX) are designed and four of them are fabricated and measured. At most of operating frequencies, the antennas exhibit impedance matching better than -10 dB and normal monopolar radiation patterns. Numerical and experimental results both confirm that the single-cell or dual-cell ENG and DNG CMTL-loaded monopoles exhibit almost identical dual ZOR modes. Moreover, the loaded elements also contribute to the radiation, which is the major advantage of this prescription over previous lumped-element loadings. These antennas are compact and the multiple operating bands can be arbitrarily engineered, enabling an alternative and easy avenue toward monopoles with multifunction and high integration.
Journal Article