Evolution of High-Energy Particle Distribution in Mature Shell-Type Supernova Remnants

Multi-wavelength observations of mature supernova remnants (SNRs), especially with recent advances in gamma-ray astronomy, make it possible to constrain energy distribution of energetic particles within these remnants. In consideration of the SNR origin of Galactic cosmic rays and physics related to particle acceleration and radiative processes, we use a simple one-zone model to fit the nonthermal emission spectra of three shell-type SNRs located within 2 degrees on the sky: RX J1713.7-3946, CTB 37B, and CTB 37A. Although radio images of these three sources all show a shell (or half-shell) structure, their radio, X-ray, and gamma-ray spectra are quite different, offering an ideal case to explore evolution of energetic particle distribution in SNRs. Our spectral fitting shows that 1) the particle distribution becomes harder with aging of these SNRs, implying a continuous acceleration process, and the particle distributions of CTB 37A and CTB 37B in the GeV range are harder than the hardest distribution that can be produced at a shock via the linear diffusive shock particle acceleration process, so spatial transport may play a role; 2) the energy loss timescale of electrons at the high-energy cutoff due to synchrotron radiation appears to be always a bit (within a factor of a few) shorter than the age of the corresponding remnant, which also requires continuous particle acceleration; 3) double power-law distributions are needed to fit the spectra of CTB 37B and CTB 37A, which may be attributed to shock interaction with molecular clouds.Comment: Accepted for publication in The Astrophysical Journal, 11 pages, 3 figures, 1 tabl

Interventions to Promote Follow-up After Trabeculectomy Surgery in Rural Southern China: A Randomized Clinical Trial.

Importance: Follow-up after trabeculectomy surgery is important to surgical success, but little is known about the effect of interventions on improving follow-up in low-resource areas.Objective: To examine whether text message reminders and free eye medications improve follow-up after trabeculectomy in rural southern China.Design, Setting, and Participants: This randomized clinical trial studied 222 consecutive patients undergoing trabeculectomy from October 1, 2014, through November 31, 2015, at 4 rural hospitals in Guangdong and Guangxi Provinces, China. Data from the intention-to-treat population were analyzed.Interventions: Patients undergoing trabeculectomy were randomized (1:1) to receive text message reminders 3 days before appointments at 1 and 2 weeks and 1 month after surgery and free topical corticosteroid medication (US$5.30) at each visit or to standard follow-up without reminders or free medication.Main Outcomes and Measure: Follow-up at 1 month postoperatively.Results: Among 222 eligible patients, 13 (5.9%) refused and 209 (94.1%) were enrolled, with 106 (50.7%) randomized to the intervention group (mean [SD] age, 64.4 [12.7] years; 56 women [52.8%]) and 103 (49.3%) to the control group (mean [SD] age, 63.0 [12.7] years; 53 women [51.5%]). A total of 6 patients (2.9%) were unavailable for follow-up. Attendance at 1 month for the intervention group (59 of 102 [57.8%]) was significantly higher than for the control group (34 of 101 [33.7%]) (unadjusted relative risk [RR], 1.72; 95% CI, 1.13-2.63; P = .01). Factors associated with 1-month attendance in multiple regression models included intervention group membership (RR, 1.65; 95% CI, 1.08-2.53; P = .02) and being told to return for suture removal (RR, 1.80; 95% CI, 1.06-3.06; P = .03). One-month attendance among controls not told about suture removal was 3 of 31 (9.7%), whereas it was 44 of 68 (64.7%) among the intervention group with suture removal (unadjusted RR, 6.69; 95% CI, 2.08-21.6; P = .001).Conclusions and Relevance: In this setting, low-cost interventions may significantly improve postoperative follow-up after glaucoma surgery, a potential opportunity for interventions known to improve surgical success.<br/

Associations between ALDOB polymorphisms and intrahepatic cholestasis of pregnancy susceptibility in the Chinese Han population

Objectives: To research the associations between fructose-bisphosphate aldolase B (ALDOB) gene polymorphisms and intrahepatic cholestasis of pregnancy (ICP) risk. Material and methods: Whole-genome sequencing (WGS) was performed to detect ALDOB polymorphisms. Five web-available tools were employed to predict the effect of the site variant on the protein. Protein structure comparisons between the reference and ALDOB-modified samples were performed by SWISS-MODEL and Chimera 1.14rc, respectively. Results: We identified 28 genetic variants in the ALDOB gene. When the cut-off value of minor allele frequency (MAF) of loci was 0.001 in four databases, five missense variants, including rs747604233, rs759204107, rs758242037, rs371526091 and rs77718928, were reserved for subsequent analysis. These variants were absent from the 1029 control individuals. The influence of all five variants on protein function was predicted to be damaging by the abovementioned five prediction software programs. Bioinformatics analysis demonstrated that these five missense variants were highly conserved among vertebrates. Compared to the wild-type protein structure, all five mutated protein structures showed a slight change in the chemical bond lengths of the enzyme activity domains. The combined clinical data indicate that the variant group had a significantly older age (p = 0.038), a higher level of indirect bilirubin (IDBIL, p = 0.033), and lower counts of white blood cells (WBCs, p = 7.38E-05) and platelets (PLTs, p = 0.018) than the wild-type group. Conclusions: This is the first study to examine the associations between ALDOB polymorphisms and ICP disease in 249 Chinese patients with ICP. Our present study expands the understanding of the pathogenesis of ICP

Novel estrogen-related gene variants identified by whole-exome sequencing in pregnancy-associated intrahepatic cholestasis

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, including fetal morbidity and mortality. It is a complex liver disorder influenced by genetic interactions, estrogen levels, and environmental factors. Although elevated estrogen levels are known to contribute to ICP pathogenesis, the role of genetic variants in estrogen-related genes remains poorly characterized. Accordingly, we conducted whole-exome sequencing (WES) in 249 patients with ICP, focusing on eight key estrogen-related genes (ESR1/2, CYP17A1/19A1, CYP1A2/1B1/3A4, and COMT). Variants were validated by Sanger sequencing and functionally characterized using comprehensive bioinformatics analyses (PolyPhen-2, SIFT, and MutationTaster) combined with molecular modeling. Our whole-exome sequencing analysis of 249 patients with ICP identified 235 variants across eight estrogen-related genes, with three novel CYP17A1 missense mutations (p.Pro28Thr, p.Phe93Leu, and p.Arg347Leu) demonstrating particularly significant findings. These variants exhibited the following characteristics: (1) complete absence in 1,237 controls and all public genomic databases (1000 Genomes, ExAC, and dbSNP); (2) evolutionary conservation of the affected residues, with unanimous pathogenic predictions from all algorithms (PolyPhen-2: damaging; SIFT: deleterious; MutationTaster: disease-causing); (3) molecular modeling demonstrating structural perturbations in critical functional domains, including steroid-binding and redox partner interaction sites. Furthermore, analysis of placental tissue revealed significantly reduced CYP17A1 expression in ICP cases versus controls (P &lt; 0.05), suggesting functional impairment of estrogen metabolic pathways. We identified three novel pathogenic CYP17A1 variants associated with ICP through whole-exome sequencing, elucidated their structural and functional effects on estrogen metabolism, and demonstrated significantly reduced placental CYP17A1 expression, thereby providing crucial insights into the genetic basis of ICP pathogenesis

Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury

As a worldwide medical problem, spinal cord injury has no clear and effective treatment to improve its prognosis. Hence, new treatment strategies for spinal cord injury with good therapeutic efficacy have been actively pursued. As a new drug loading system, acetal dextran nanoparticles (SAD) have good biocompatibility and biodegradability. Therefore, we designed spermine-functionalized acetal-dextran (SAD) nanoparticles and encapsulated paclitaxel (PCL) into them. This design can ensure the sustained release of paclitaxel in the injured area for 4 days and promote the extension of nerve processes in vitro. In our experiment, we found that paclitaxel-loaded SAD nanoparticles (PCL@SAD) decreased the level of chondroitin sulfate proteoglycan in the rat spinal cord injury model, which reduced the scar repair of the injured site and changed the inhibitory environment after spinal cord injury. This reveals that PCL@SAD can effectively protect the injured spinal cord and ultimately improve the functional recovery of the injured spinal cord. One single injection of PCL@SAD shows better therapeutic effect than that of PCL. This study opens an exciting perspective toward the application of neuroprotective PCL@SAD for the treatment of severe neurological diseases