Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light and play roles in non-image forming vision, such as circadian rhythms, pupil responses, and sleep regulation, or image ...forming vision, such as processing visual information and directing eye movements in response to visual clues. The purpose of the present study was to identify the distribution, types, and proportion of melanopsin-immunoreactive (IR) cells in the retina of a nocturnal animal, i.e., the microbat (Rhinolophus ferrumequinum). Three types of melanopsin-IR cells were observed in the present study. The M1 type had dendritic arbors that extended into the OFF sublayer of the inner plexiform layer (IPL). M1 soma locations were identified either in the ganglion cell layer (GCL, M1c; 21.00%) or in the inner nuclear layer (INL, M1d; 5.15%). The M2 type had monostratified dendrites in the ON sublayer of the IPL and their cell bodies lay in the GCL (M2; 5.79%). The M3 type was bistratified cells with dendrites in both the ON and OFF sublayers of the IPL. M3 soma locations were either in the GCL (M3c; 26.66%) or INL (M3d; 4.69%). Additionally, some M3c cells had curved dendrites leading up towards the OFF sublayer of the IPL and down to the ON sublayer of the IPL (M3c-crv; 7.67%). Melanopsin-IR cells displayed a medium soma size and medium dendritic field diameters. There were 2-5 primary dendrites and sparsely branched dendrites with varicosities. The total number of the neurons in the GCL was 12,254.17 ± 660.39 and that of the optic nerve axons was 5,179.04 ± 208.00 in the R. ferrumequinum retina. The total number of melanopsin-IR cells was 819.74 ± 52.03. The ipRGCs constituted approximately 15.83% of the total RGC population. This study demonstrated that the nocturnal microbat, R. ferrumequinum, has a much higher density of melanopsin-IR cells than documented in diurnal animals.
The role of ascorbate (AsA) in antioxidant defense system-associated resistance to cadmium (Cd) in oilseed rape plants has not yet been clearly demonstrated. The present study investigated the ...critical role of exogenous AsA on the physiological and biochemical responses of reactive oxygen species (ROS) and antioxidant scavenging defense systems in oilseed rape (
L. cv. Tammi) seedlings exposed to Cd. Cd (10 μM) treatment led to significant reductions in plant growth; increases in the levels of superoxide anion radical, hydrogen peroxide, and malondialdehyde; and increases in Cd uptake and accumulation by the roots and shoots in hydroponically grown 10-day-old seedlings. Moreover, it reduced AsA content and AsA redox ratios, which have been correlated with reductions in glutathione (GSH) and/or nicotinamide adenine dinucleotide phosphate (NADPH) redox status. However, exogenously applying AsA to Cd-exposed seedlings decreased Cd-induced ROS, improved antioxidant defense systems by increasing AsA, GSH, and NADPH contents, and increased Cd uptake and accumulation in both roots and shoots of the plants. These results provided evidence that the enhancement in AsA redox status can be linked to an increase in the GSH and/or NADPH redox ratios through the induction of the AsA-GSH-NADPH cycle. Thus, these results suggest that exogenous AsA application to oilseed rape seedlings under Cd stress might alleviate the overall Cd toxicity by regulating the homeostasis of the AsA-GSH-NADPH cycle, which reestablishes the steady-state cellular redox status.
Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
This study investigates the positive and negative effects of developmental job experience (DJE) on employees’ innovative behavior. Relying on transactional stress theory, we hypothesize the mediating ...roles of psychological capital and burnout in the relationship between DJE and innovative behavior as assessed by team leaders. The results reveal that DJE is only indirectly related to innovative behavior via psychological capital and burnout when employees’ perceived job mobility within an organization (PJM) is low (moderated mediation). We also find that employees’ PJM significantly and differentially moderates the relationships between DJE and psychological capital and between DJE and burnout. Our study provides both theoretical and practical guidance on how to utilize developmental jobs to promote employees’ innovative behavior.
Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large ...B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy.
The antioxidant glutathione (GSH) mitigates adverse physio-metabolic effects and defends against abiotic types of stress, such as cadmium (Cd) stress. However, its function and role in resisting Cd ...phytotoxicity by leveraging plant antioxidant-scavenging, redox-regulating, and hormone-balancing systems have not been comprehensively and systematically demonstrated in the Cd-hyperaccumulating plant
Brassica napus
L. cv. Tammi (oilseed rape). In this study, the effects of exogenously applied GSH to the leaves of
B. napus
seedlings exposed to Cd (10 μM) were investigated. As a result, Cd stress alone significantly inhibited growth and increased the levels of reactive oxygen species (ROS) and the bioaccumulation of Cd in the seedlings compared with those in unstressed controls. Furthermore, Cd stress induced an imbalance in plant stress hormone levels and decreases in endogenous GSH levels and GSH redox ratios, which were correlated with reductions in ascorbate (AsA) and/or nicotinamide adenine dinucleotide phosphate (NADPH) redox states. However, the exogenous application of GSH to Cd-stressed
B. napus
seedlings reduced Cd-induced ROS levels and enhanced antioxidant-scavenging defenses and redox regulation by both increasing seedling AsA, GSH, and NADPH concentrations and rebalancing stress hormones, thereby enhancing Cd uptake and accumulation. These results demonstrate that GSH improved plant redox status by upregulating the AsA-GSH-NADPH cycle and reestablishing normal hormonal balance. This indicates that exogenously applied GSH can mitigate Cd phytotoxicity in
B. napus
and possibly other plants. Therefore, GSH can potentially be applied to Cd-polluted soil for plant remediation.
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