THE EFFECTS OF VISUAL PROMPT ON PEDESTRIAN SAFETY

Since 2005, pedestrian deaths nationwide had decreased by more than 16 percent, averaging about 200 fewer deaths per year. However, preliminary data collected from the first six months of 2010 show that the decrease had apparently slowed or stopped--seven more pedestrians died in the first six months of 2010 than for the same period in 2009 (Fogel, 2011). Car - pedestrian collisions at crosswalks were serious matters that required continuous research on increasing pedestrian safety at crosswalks. In this paper, although (e.g., Cox, et al., 2010; Houten & Retting, 2001; Huybers, Van Houten, & Malenfant, 2004; Reagan, Sifrit, Compton, Tenebaum, & Van Houten, 2010) have all contributed to the behavior interventions in pedestrian safety, we followed the procedure of earlier research conducted by Crowley-Koch et al. (2011) on the effects of pedestrian prompts on motorist yielding at crosswalks. In addition, this current study extended the previous study by examining the effects of a pedestrian prompt through a wearing of a Bell® Spider flasher over left arm at resting position, on motorist yielding at a controlled crosswalk. Implications and future directions are discussed

Clinicopathologic characteristics of extramammary Paget’s disease of the scrotum associated with sweat gland adenocarcinoma—a clinical retrospective study

Extramammary Paget’s disease of the scrotum with sweat gland adenocarcinoma is a rare malignant tumor. This study aims to summarize the clinicopathologic characteristics related to the prognosis of scrotal Paget’s disease with underlying sweat gland adenocarcinoma. Clinical datum of four patients with scrotal Paget’s disease with sweat gland carcinoma, treated in Beijing Chao-Yang Hospital from 2002 to 2009 was analyzed, and a literature review was conducted. The typical manifestation of scrotal Paget’s disease with sweat gland carcinoma was eczematoid-like skin lesions. All patients underwent primary lesion resection plus inguinal lymphadenectomy. Three patients had inguinal lymph metastasis. One of them developed distant metastases in bone and bone marrow and died of metastatic carcinoma. The dead patient had higher serum carcinoma embryonic antigen (CEA) level, Her-2 overexpression and shorter disease course than the other patients. The other patients were observed for at least 3 years, and lived without tumor. Scrotal Paget’s disease with sweat gland adenocarcinoma may be prone to inguinal lymph node and bone metastasis. Serum CEA level, Her-2 overexpression, dermis and lymphovascular invasion may be associated with the prognosis of scrotal Paget’s disease with sweat gland adenocarcinoma. The primary lesion resection plus inguinal lymphadenectomy is the major treatment for scrotal Paget’s disease with sweat gland adenocarcinoma. The effect of combination chemotherapy in the treatment of metastatic extramammary Paget’s disease remains to be proven by prolonged follow-up and wide experience

OsMADS1 represses microRNA172 in elongation of palea/lemma development in Rice

Specification of floral organ identity is critical for the establishment of floral morphology and inflorescence architecture. Although multiple genes are involved in the regulation of floral organogenesis, our understanding of the underlying regulating network is still fragmentary. MADs-box genes are principle members in the ABC model that characterized floral organs. OsMADS1 specifies the determinacy of spikelet meristem and lemma/palea identity in rice. However, the pathway through which OsMADS1 regulates floral organs remains elusive; here, we identified the miR172 family as possible regulators downstream of OsMADS1. Genetic study revealed that overexpression of each miR172 gene resulted in elongated lemma/palea and indeterminacy of the floret, which resemble the phenotype of osmads1 mutant. On the contrary, overexpression of each target APETALA2 (AP2) genes resulted in shortened palea/lemma. Expression level and specificity of miR172 was greatly influenced by OsMADS1, as revealed by Northern blot analysis and In situ hybridization. Genetically, AP2-3 and AP2-2 over expression complemented the elongation and inconsistent development of the lemma/palea in OsMADS1RNAi transgenic plants. Our results suggested that in rice, OsMADS1 and miR172s/AP2s formed a regulatory network involved in floral organ development, particularly the elongation of the lemma and the palea

Targeted Co-Delivery of Gefitinib and Rapamycin by Aptamer-Modified Nanoparticles Overcomes EGFR-TKI Resistance in NSCLC via Promoting Autophagy

Acquired drug resistance decreases the efficacy of gefitinib after approximately 1 year of treatment in non-small-cell lung cancer (NSCLC). Autophagy is a process that could lead to cell death when it is prolonged. Thus, we investigated a drug combination therapy of gefitinib with rapamycin—a cell autophagy activator—in gefitinib-resistant NSCLC cell line H1975 to improve the therapeutic efficacy of gefitinib in advanced NSCLC cells through acute cell autophagy induction. Cell viability and tumor formation assays indicated that rapamycin is strongly synergistic with gefitinib inhibition, both in vitro and in vivo. Mechanistic studies demonstrated that EGFR expression and cell autophagy decreased under gefitinib treatment and were restored after the drug combination therapy, indicating a potential cell autophagy–EGFR positive feedback regulation. To further optimize the delivery efficiency of the combinational agents, we constructed an anti-EGFR aptamer-functionalized nanoparticle (NP-Apt) carrier system. The microscopic observation and cell proliferation assays suggested that NP-Apt achieved remarkably targeted delivery and cytotoxicity in the cancer cells. Taken together, our results suggest that combining rapamycin and gefitinib can be an efficacious therapy to overcome gefitinib resistance in NSCLC, and targeted delivery of the drugs using the aptamer-nanoparticle carrier system further enhances the therapeutic efficacy of gefitinib

Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis

Abstract Background Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle‐specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored. Methods RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1SC/WT and Tfr1SC/KO (n = 6–8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects. Results By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell‐autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin‐1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus‐expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin‐1 to improve running time (P = 0.0257) and distance (P = 0.0248). Conclusions Satellite cell‐specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases