Glutathione de Novo Synthesis but Not Recycling Process Coordinates with Glutamine Catabolism to Control Redox Homeostasis and Directs Murine T Cell Differentiation

Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells

Flat feline faces: is brachycephaly associated with respiratory abnormalities in the domestic cat (Felis catus)?

There has been little research into brachycephalism and associated disorders in cats. A questionnaire aimed at cat owners was used to determine the relationship between feline facial conformation and owner-reported cat management requirements and respiratory abnormalities. Owner-submitted photographs of cats were used to develop novel measures of skull conformation. One thousand valid questionnaires were received. Within these there were 373 valid photographs that allowed measurement of muzzle ratio (M%) and 494 that allowed nose position ratio (NP%). The data included 239 cats for which both measurements were available. Owners reported lifestyle factors (e.g. feeding type, grooming routine, activity level), physical characteristics (e.g. hair length) and other health characteristics of their cat (e.g. tear staining, body condition score). A composite respiratory score (RS) was calculated for each cat using their owner’s assessment of respiratory noise whilst their cat was asleep and then breathing difficulty following activity. Multivariate analyses were carried out using linear models to explore the relationship between RS and facial conformation, and lifestyle risk factors. The results showed that reductions in NP% and M% were significantly associated with RS (P < 0.001 and P = 0.026, respectively) and that the relationship was significantly negatively correlated (r = -0.56, P < 0.001 for both). Respiratory score was also significantly associated with increased presence of tear staining (P < 0.001) and a sedentary lifestyle (P = 0.01). This study improves current knowledge concerning cats with breeding-related alterations in skull confirmation and indicates that brachycephalism may have negative respiratory implications for cat health and welfare, as has been previously shown in dogs

Spatial−temporal variation of ecological environment quality and driving factors from 2000 to 2020 in Wuliangsu Lake Basin, Northern China

Due to global climate change and the intensification of human activities, the ecological function of Wuliangsu Lake Basin has been seriously degraded. Obtaining accurate spatial–temporal dynamics of regional ecological environment quality is essential for the evaluation of ecological management and restoration effects. This study assessed the trend changes and drivers of the Remote Sensing Ecological Index (RSEI) in the Wuliangsu Lake Basin from 2000−2020. Firstly, the trend analysis method and hurst index were used to analyze the temporal and spatial variation of RSEI. Then the main factors of RSEI variation were analyzed using meteorological data, integrated nighttime lighting data, and population density data. Overall, the RSEI shows an increasing trend from the west to the east with a rate of 0.0034 year−1 over the last 21 years. The area change of RSEI was 54.22%, 63.80% and 52.43% for 2000−2006, 2007−2013 and 2014−2020, respectively, which indicates that most areas have a stable ecological environment. However, the overall Future Improvement Trend (FIT) area of RSEI is 42.21%, mainly in Dengkou area, Urad Qianqi and central area. This indicates that the RSEI remains stable locally and shows an overall improving trend. The results of the correlation analysis showed that the areas influenced by meteorological and human factors were highly coincident, mainly in Dengkou and northern Linhe areas and Urad Qianqi. Considering the lagging effect of ecological engineering, the sustainable development status of RSEI in the western and eastern regions will maintain an improving trend in the future. Our study confirms the complex relationship between RSEI and meteorological and human activities, which is crucial for the scientific management of watershed ecosystems under the influence of anthropogenic factors

COVID-19 Vaccination Status and Hesitancy among Breast Cancer Patients after Two Years of Pandemic: A Cross-Sectional Survey

Background: Patients with cancer show greater susceptibility and vulnerability to severe acute respiratory syndrome coronavirus 2 infection. However, data on the vaccination status among patients with breast cancer and any structured analysis of the factors influencing patients&rsquo; decisions regarding vaccines are lacking. Methods: This cross-sectional study on patients with breast cancer in China was conducted from 1 June 2022, to 17 June 2022. Every participant completed an online questionnaire about their vaccination status and any adverse reactions, and a scale based on the Health Belief Model (HBM) to assess the vaccination status of respondents and their willingness to receive following doses or boosters. Results: Among the 1132 participants, 55.2% had received a COVID-19 vaccine. The incidence of adverse events per dose was around 40%. Vaccine hesitancy of 61.9% was observed among patients who had not fully received three doses of vaccine or boosters. The only variable found to be associated with vaccine hesitancy was time since diagnosis (p &lt; 0.05). In the HBM scale, vaccine hesitancy was closely related to a low level of perceived susceptibility, a low level of perceived benefit, a high level of perceived barriers and a low level of agreement with doctors&rsquo; advice. Conclusions: For patients with breast cancer, perceived susceptibility, benefits and barriers should be prioritized, and the advice from authoritative doctors is a vital cue to action

A nomogram for predicting breast cancer specific survival in elderly patients with breast cancer: a SEER population-based analysis

Abstract Background The number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients. Methods We identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model. Results A total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts. Conclusions Our study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making

Multivariate model of the relationship between respiratory score (RS) and skull conformation, health and lifestyle variables.

<p>Multivariate model of the relationship between respiratory score (RS) and skull conformation, health and lifestyle variables.</p

Calculation of Proportional muzzle length ratio (M%).

<p>Cranial length is defined as the horizon-line distance (mm) from the dorsal tip of the nose to the occipital protuberance (b’-c). Muzzle length is the horizon-line distance (mm) from the dorsal tip of nose to the nasal stop (b’-b). In the event that the dorsal tip of the nose is in line with the nasal stop a zero value is assigned. For this picture M% = 7.89% ([muzzle length 6mm / cranial length 76mm] *100). Note for readers: measurements will differ based on the size of viewed image.</p