Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that threatens the vision of premature infants. Various novel drugs have demonstrated therapeutic potential for ROP by targeting signaling pathways associated with vascular endothelial growth factor (VEGF) [such as PI3K/AKT, hypoxia-inducible factor (HIF)-1α/VEGF], oxidative stress, tumor necrosis factor (TNF)-α, and Notch pathways. Propranolol, insulin-like growth factor-1, and celecoxib attenuate pathological neovascularization via the PI3K/Akt signaling pathway. Tripterine and melatonin inhibit retinal neovascularization by modulating the HIF-1α/VEGF signaling axis. Adiponectin mitigates the damage caused by oxidative stress and preserves endothelial function by enhancing endothelial nitric oxide synthase activity. Omega-3 polyunsaturated fatty acids suppress TNF-α-mediated inflammatory responses, modulate retinal development and angiogenesis, and reduce retinal neovascular lesions. DAPT, a γ-secretase inhibitor, blocks Notch signaling to suppress abnormal vascular proliferation. These agents exhibit synergistic multi-pathway anti-angiogenic effects in preclinical models and early-phase clinical trials, offering critical insights for advancing drug development and clinical translation in ROP management.
Retinopathy of Prematurity/metabolism* ; Humans ; Signal Transduction/drug effects* ; Infant, Newborn ; Vascular Endothelial Growth Factor A/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Oxidative Stress/drug effects* ; Fatty Acids, Omega-3/therapeutic use* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Receptors, Notch/metabolism* ; Angiogenesis Inhibitors/therapeutic use* ; Insulin-Like Growth Factor I/therapeutic use*

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective:To analyze the characteristics of adults (non-pregnant women) infected with Listeria monocytogenes and to provide evidence for diagnosis and treatment of this disease. Methods:Patients admitted in West China Hospital of Sichuan University between January 2008 and April 2020 with Listeriadisease were enrolled in this study. The clinical data of patients including age, symptoms, underlying diseases and prognosis, as well as the laboratory results of WBC, neutrophil ratio (N%), procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), were obtained for analyzing the clinical infection and prognosis characteristics of the patients. Results:A total of 57 patients were included, patients were 18-83 (52.8±15.9) years old, percent of over 60 years old patients accounted for 35.09% (20/57). The incidence rate in summer season was the highest (45.61%, 26/57). There were 48 cases with comorbidities, sepsis occurred in 31 cases and meningitis in 18 cases. The time of diagnosis of Listeriosis was (6.1±2.9) days. After diagnosis, the target therapy was applied: such as carbapenem (26.32%, 15/57) and penicillins (22.81%, 13/57). The levels of WBC (6.77 [2.99, 9.54]×10 9/L vs 10.23 [6.71, 16.55]×10 9/L), NLR (3.07 [1.66, 8.16] vs 11.26 [5.66, 20.08]) and CRP (40.7 [16.9, 91.9] g/L vs 92.8 [59.9, 142.7] g/L) were significantly lower after treatment than those before treatment in 47 hospitalized patients (all P<0.05). Thirty-eight patients were treated according to the guidelines, 33 cases improved, 2 cases had poor prognosis and 2 cases died. Conclusion:The main risk factors of Listeria monocytogenes infection in adults (non-pregnant women) are underlying diseases, especially autoimmune diseases and pulmonary infections. Penicillins can be used as the first choice for empirical therapy. Carbapenems and erythromycin serve as the combination medications during the full course of treatment.

Objective To investigate the epidemiology of BDV infection in Yili horses and Yili donkeys and to analyze phylogenetic source of BDV in Yili area, Xinjiang. Methods We established fluo- rescence quantitative nested RT-PCR to detect BDV p24 segment in peripheral blood mononuclear cells (PBMCs) of 518 Yili horses and 206 Yili donkeys in Yili area, Xinjiang. Positive products were validated by detecting BDV p40 segment and plasmid to preclude the contamination, and were sequenced to analyze the homology of gene sequence, amino acid sequence and phylogenetic tree. Results The positive rates of BDV infection in PBMCs of 518 Yili horses and 206 Yili donkeys were 0.97% and 1.94%, respectively. The results of BDV p40 segment verification were positive in all of the samples of BDV p24 positive. All the samples tested were not contaminated by plasmid. There was a homology of the gene sequence of positive PCR samples with strain He/80. And the gene sequence revealed more than 93% identical to H1766 and strain V. Conclusion Our study suggested BDV natural infection in Yili horses and Yili donkeys. The en- demic BDV had a high degree of identity to strain He/80.