Shaping school for childhood myopia: the association between floor area ratio of school environment and myopia in China.

AIM: To investigate the association of floor area ratio (FAR), an indicator of built environments, and myopia onset. METHODS: This prospective cohort study recruited 136 753 children aged 6-10 years from 108 schools in Shenzhen, China at baseline (2016-2017). Refractive power was measured with non-cycloplegic autorefraction over a 2-year follow-up period. FAR was objectively evaluated using geographical information system technology. Mixed-effects logistic regression models were constructed to examine the association of FAR with a 2-year cumulative incidence of myopia among individuals without baseline myopia; multiple linear regression model, with a 2-year cumulative incidence rate of myopia at each school. RESULTS: Of 101 624 non-myopic children (56.3% boys; mean (SE) age, 7.657±1.182 years) included in the study, 26 391 (26.0%) of them developed myopia after 2 years. In the individual-level analysis adjusting for demographic, socioeconomic and greenness factors, an IQR in FAR was associated with a decreased risk of 2-year myopia incidence (OR 0.898, 95% CI 0.866 to 0.932, p<0.001). Similar findings were observed in the analysis additionally adjusted for genetic and behavioural factors (OR 0.821, 95% CI 0.766 to 0.880, p<0.001). In the school-level, an IQR increase in FAR was found to be associated with a 2.0% reduction in the 2-year incidence rate of myopia (95% CI 1.3% to 2.6%, p<0.001). CONCLUSIONS: Exposure to higher FAR was associated with a decreased myopia incidence, providing insights into myopia prevention through school built environments in China.

Direct synthesis of controllable ultrathin heteroatoms-intercalated 2D layered materials.

Two-dimensional (2D) layered materials have been studied in depth during the past two decades due to their unique structure and properties. Transition metal (TM) intercalation of layered materials have been proven as an effective way to introduce new physical properties, such as tunable 2D magnetism, but the direct growth of atomically thin heteroatoms-intercalated layered materials remains untapped. Herein, we directly synthesize various ultrathin heteroatoms-intercalated 2D layered materials (UHI-2DMs) through flux-assisted growth (FAG) approach. Eight UHI-2DMs (V1/3NbS2, Cr1/3NbS2, Mn1/3NbS2, Fe1/3NbS2, Co1/3NbS2, Co1/3NbSe2, Fe1/3TaS2, Fe1/4TaS2) were successfully synthesized. Their thickness can be reduced to the thinnest limit (bilayer 2D material with monolayer intercalated TM), and magnetic ordering can be induced in the synthesized structures. Interestingly, due to the possible anisotropy-stabilized long-range ferromagnetism in Fe1/3TaS2 with weak interlayer coupling, the layer-independent magnetic ordering temperature of Fe1/3TaS2 was revealed by magneto-transport properties. This work establishes a general method for direct synthesis of heteroatom-intercalated ultrathin 2D materials with tunable chemical and physical properties.

Development and Evaluation of a Retrieval-Augmented Large Language Model Framework for Ophthalmology.

Importance: Although augmenting large language models (LLMs) with knowledge bases may improve medical domain-specific performance, practical methods are needed for local implementation of LLMs that address privacy concerns and enhance accessibility for health care professionals. Objective: To develop an accurate, cost-effective local implementation of an LLM to mitigate privacy concerns and support their practical deployment in health care settings. Design, Setting, and Participants: ChatZOC (Sun Yat-Sen University Zhongshan Ophthalmology Center), a retrieval-augmented LLM framework, was developed by enhancing a baseline LLM with a comprehensive ophthalmic dataset and evaluation framework (CODE), which includes over 30 000 pieces of ophthalmic knowledge. This LLM was benchmarked against 10 representative LLMs, including GPT-4 and GPT-3.5 Turbo (OpenAI), across 300 clinical questions in ophthalmology. The evaluation, involving a panel of medical experts and biomedical researchers, focused on accuracy, utility, and safety. A double-masked approach was used to try to minimize bias assessment across all models. The study used a comprehensive knowledge base derived from ophthalmic clinical practice, without directly involving clinical patients. Exposures: LLM response to clinical questions. Main Outcomes and Measures: Accuracy, utility, and safety of LLMs in responding to clinical questions. Results: The baseline model achieved a human ranking score of 0.48. The retrieval-augmented LLM had a score of 0.60, a difference of 0.12 (95% CI, 0.02-0.22; P = .02) from baseline and not different from GPT-4 with a score of 0.61 (difference = 0.01; 95% CI, -0.11 to 0.13; P = .89). For scientific consensus, the retrieval-augmented LLM was 84.0% compared with the baseline model of 46.5% (difference = 37.5%; 95% CI, 29.0%-46.0%; P < .001) and not different from GPT-4 with a value of 79.2% (difference = 4.8%; 95% CI, -0.3% to 10.0%; P = .06). Conclusions and Relevance: Results of this quality improvement study suggest that the integration of high-quality knowledge bases improved the LLM's performance in medical domains. This study highlights the transformative potential of augmented LLMs in clinical practice by providing reliable, safe, and practical clinical information. Further research is needed to explore the broader application of such frameworks in the real world.

[Effect of gestational weight gain on growth trajectory in children aged 0 to 3 years].

OBJECTIVE: To describe the growth trajectory of body mass index for age Z score(BAZ) in children aged 0 to 3 years and to explore the association between gestational weight gain and BAZ growth trajectory. METHODS: Based on a prospective cohort study, we recruited pregnant women in their early pregnancy into this study from 2013 to 2017 in Taicang of Jiangsu Province, tracked their weight changes until they gave birth, and calculated and evaluated their gestational weight gain(GWG) as appropriate, inadequate or excessive GWG based on Chinese GWG standard. Children's height/length and weight were measured at birth, 1, 3, 6, 8, 12, 18, 24, 30 and 36 months of age, and their BAZ scores were calculated. Group-based trajectory modeling(GBTM) was used for fitting BAZ trajectories. Multilevel Logistic regression was used to analyze the association between the level of GWG and BAZ growth trajectories. RESULTS: There were 1864 mother-child pairs in the study, and three groups of BAZ trajectories were fitted including slow growth trajectory(34.07%), appropriate growth trajectory(48.23%), and fast growth trajectory(17.70%). In univariate analysis, compared with children whose mothers had appropriate GWG, the children whose mothers had inadequate GWG were more likely in the group of slow growth trajectory(OR = 1.95, 95%CI 1.28-2.96), and the children whose mothers had excessive GWG were more likely in the group of fast growth trajectory(OR = 1.57, 95% CI 1.19-2.07). After adjusting for maternal pre-pregnancy body mass index(BMI) and parity, and the child's gender and birth weight, the children whose mothers gained in adequate GWG were more likely in the group of slow growth trajectory(OR = 1.84, 95%CI 1.19-2.84), while the association between excessive GWG and fast growth trajectory was not statistically significant(OR = 1.26, 95%CI 0.94-1.68). CONCLUSION: The BAZ trajectories of children aged 0-3 years can be categorized into slow, appropriate, and fast growth groups, and children's slow growth was associated with maternal inadequate GWG.

COL5A2 drives regorafenib resistance-induced metastatic phenotype via reducing LIFR expression in hepatocellular carcinoma.

Systemic therapies, the ultimate strategies for patients with advanced hepatocellular carcinoma (HCC), are suffering from serious clinical challenges, such as the occurrence and development of drug resistance. Treatment resistance aggravates tumor progression partly by inducing tumor metastasis. Regorafenib-resistant HCC cells exhibit a highly striking metastatic phenotype, but the detailed mechanisms underlying these aggressive behaviors remain elusive. Here, we conduct transcriptome sequencing analysis to identify COL5A2 as a crucial driver of the metastatic characteristics of regorafenib-resistant HCC cells. COL5A2 is aberrantly highly expressed in resistant cells, and its genetic depletion significantly suppresses proliferation, migration, invasion, vasculogenic mimicry (VM) formation and lung metastasis in vitro and in vivo, concomitant with the downregulation of VE-cadherin, EphA2, Twist1, p-p38 and p-STAT3 expressions. LIFR is confirmed to be an essential downstream molecule of COL5A2, and its expression is observably elevated by COL5A2 depletion. Ectopic overexpression of LIFR drastically attenuates the proliferation, migration, invasion and VM of regorafenib-resistant cells and represses the expressions of VM-related molecules and the activation of p38/STAT3 signaling pathway. Interestingly, rescue experiments show that the inhibition of the above aggressive features of resistant cells by COL5A2 loss is clearly alleviated by silencing of LIFR. Collectively, our results reveal that COL5A2 promotes the ability of regorafenib-resistant HCC cells to acquire a metastatic phenotype by attenuating LIFR expression and suggest that therapeutic regimens targeting the COL5A2/LIFR axis may be beneficial for HCC patients with therapeutic resistance.

Ion Transport Behavior in van der Waals Gaps of 2D Materials.

2D materials, with advantages of atomic thickness and novel physical/chemical characteristics, have emerged as the vital building blocks for advanced lamellar membranes which possess promising potential in energy storage, ion separation, and catalysis. When 2D materials are stacked together, the van der Waals (vdW) force generated between adjacent layered nanosheets induces the construction of an ordered lamellar membrane. By regulating the interlayer spacing down to the nanometer or even sub-nanometer scale, rapid and selective ion transport can be achieved through such vdW gaps. The further improvement and application of qualified 2D materials-based lamellar membranes (2DLMs) can be fulfilled by the rational design of nanochannels and the intelligent micro-environment regulation under different stimuli. Focusing on the newly emerging advances of 2DLMs, in this review, the common top-down and bottom-up synthesis approaches of 2D nanosheets and the design strategy of functional 2DLMs are briefly introduced. Two essential ion transport mechanisms within vdW gaps are also involved. Subsequently, the responsive 2DLMs based on different types of external stimuli and their unique applications in nanofluid transport, membrane-based filters, and energy storage are presented. Based on the above analysis, the existing challenges and future developing prospects of 2DLMs are further proposed.

Front-of-Package-Label-Style Health Logos on Menus-Do Canadian Consumers Really Care about Menu Health Logos?

Public health policies have been widely utilized to improve population nutrition, such as the newly announced front-of-pack labels (FOPLs) that will be applied to Canadian prepackaged foods to help consumers make healthier selections. However, research on similar health logos in the food service sector has been limited. This study explores the potential application of FOPL-style health logos in the food service sector and its impact on consumer behaviors. A survey was conducted among 1070 Canadians to assess their awareness, perception, and support for health logos on restaurant menus. The results indicate that while participants value healthy food options when dining out, taste, price, and convenience remain the primary factors influencing their choices. Most participants were unaware of existing FOPL policies and demonstrated mixed responses regarding the influence of similar health logos on their restaurant selection. However, a majority expressed a desire to see FOPL-style health logos on menus, and nutrient profile ratings and logos indicating nutrient limitations or encouragements were listed as preferred health logos. Notably, females indicated higher supportiveness for FOPL-style health logos on menus and individuals with food allergies exhibited higher agreement in the likelihood of eating at a restaurant displaying labels. Additionally, findings revealed that FOPL-style health logos alone may not significantly deter consumers from purchasing labelled menu items, especially if price is affected. Overall, this study highlights the need for further understanding consumer perceptions to effectively develop and implement FOPL initiatives in the food service sector.

Green Space Morphology and School Myopia in China.

Importance: China has experienced both rapid urbanization and major increases in myopia prevalence. Previous studies suggest that green space exposure reduces the risk of myopia, but the association between myopia risk and specific geometry and distribution characteristics of green space has yet to be explored. These must be understood to craft effective interventions to reduce myopia. Objective: To evaluate the associations between myopia and specific green space morphology using novel quantitative data from high-resolution satellite imaging. Design, Setting, and Participants: This prospective cohort study included students grades 1 to 4 (aged 6 to 9 years) in Shenzhen, China. Baseline data were collected in 2016-2017, and students were followed up in 2018-2019. Data were analyzed from September 2020 to January 2022. Exposures: Eight landscape metrics were calculated using land cover data from high-resolution Gaofen-2 satellite images to measure area, aggregation, and shape of green space. Main Outcome and Measures: The 2-year cumulative change in myopia prevalence at each school and incidence of myopia at the student level after 2 years were calculated as main outcomes. The associations between landscape metrics and school myopia were assessed, controlling for geographical, demographic, and socioeconomic factors. Principal component analyses were performed to further assess the joint effect of landscape metrics at the school and individual level. Results: A total of 138 735 students were assessed at baseline. Higher proportion, aggregation, and better connectivity of green space were correlated with slower increases in myopia prevalence. In the principal component regression, a 1-unit increase in the myopia-related green space morphology index (the first principal component) was negatively associated with a 1.7% (95% CI, -2.7 to -0.6) decrease in myopia prevalence change at the school level (P = .002). At the individual level, a 1-unit increase in myopia-related green space morphology index was associated with a 9.8% (95% CI, 4.1 to 15.1) reduction in the risk of incident myopia (P < .001), and the association remained after further adjustment for outdoor time, screen time, reading time, and parental myopia (adjusted odds ratio, 0.88; 95% CI, 0.80 to 0.97; P = .009). Conclusions and Relevance: Structure of green space was associated with a decreased relative risk of myopia, which may provide guidance for construction and renovation of schools. Since risk estimates only indicate correlations rather than causation, further interventional studies are needed to assess the effect on school myopia of urban planning and environmental designs, especially size and aggregation metrics of green space, on school myopia.

Application Value of Antimicrobial Peptides in Gastrointestinal Tumors.

Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate immune defense of many organisms, antimicrobial peptides not only have broad-spectrum antibacterial activity but also can specifically kill tumor cells. The positive charge of antimicrobial peptides under neutral conditions determines their high selectivity to tumor cells. In addition, antimicrobial peptides also have unique anticancer mechanisms, such as inducing apoptosis, autophagy, cell cycle arrest, membrane destruction, and inhibition of metastasis, which highlights the low drug resistance and high specificity of antimicrobial peptides. In this review, we summarize the related studies on antimicrobial peptides in the treatment of digestive tract tumors, mainly oral cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. This paper describes the therapeutic advantages of antimicrobial peptides due to their unique anticancer mechanisms. The length, net charge, and secondary structure of antimicrobial peptides can be modified by design or modification to further enhance their anticancer effects. In summary, as an emerging cancer treatment drug, antimicrobial peptides need to be further studied to realize their application in gastrointestinal cancer diseases.

Heterogeneity of Phase II Enzyme Ligands on Controlling the Progression of Human Gastric Cancer Organoids as Stem Cell Therapy Model.

Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC.

Breast-conserving surgery is an appropriate procedure for centrally located breast cancer: a population-based retrospective cohort study.

BACKGROUND: The evidence of breast-conserving therapy (BCT) applied in centrally located breast cancer (CLBC) is absent. This study aims to investigate the long-term survival of breast-conserving therapy (BCT) in centrally located breast cancer (CLBC) compared with mastectomy in CLBC and BCT in non-CLBC. METHODS: Two hundred ten thousand four hundred nine women with unilateral T1-2 breast cancer undergoing BCT or mastectomy were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival curves were assessed via log-rank test. Propensity score matching (PSM) was used to balance baseline features, and the multivariable Cox model was used to estimate the adjusted hazard ratio [HR] and its 95% confidence interval [CI] for breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: With a median follow-up of 91 months, the BCSS and OS rates in patients who received BCT were greater than those patients treated with mastectomy in the entire CLBC set. Multivariable Cox analyses showed that CLBC patients who received BCT had better BCSS (HR = 0.67, 95%CI: 0.55-0.80, p < 0.001) and OS (HR = 0.78, 95%CI: 0.68-0.90, p = 0.001) than patients who received a mastectomy, but there were no significant differences of BCSS (HR = 0.65, 95%CI: 0.47-0.90, p = 0.009) and OS (HR = 0.82, 95%CI: 0.65-1.04, p = 0.110) after PSM. In patients treated with BCT, CLBC patients had a similar BCSS (HR = 0.99, 95%CI: 0.87-1.12, p = 0.850) but a worse OS (HR = 1.09, 95%CI: 1.01-1.18, p = 0.040) compared to that of the non-CLBC patient, but there was no significant difference both BCSS (HR = 1.05, 95%CI: 0.88-1.24, p = 0.614) and OS (HR = 1.08, 95%CI: 0.97-1.20, p = 0.168) after PSM. CONCLUSION: Our findings revealed that BCT should be an acceptable and preferable alternative to mastectomy for well-selected patients with CLBC.

Examining the Role of Big Data and Block Chain Technology in Advancing High-Quality Development within the Sports Industry's Digital Economy / Examinando el papel de Big Data y la tecnología Block Chain en el avance del desarrollo de alta calidad dentro de la economía digital de la industria del deporte

In the ever-evolving landscape of the global economy, big data, the new generation of artificial intelligence, and block chain technology have risen as pivotal drivers of the data economy. These technologies are playing an increasingly vital role in catalyzing transformative changes within the sports industry and the broader digital economy. As the world economic patterns continue to shift and Internet technologies advance, the digital economy, particularly within the sports sector, faces higher demands and opportunities for innovation. In the context of China's economic development, the digital economy has emerged as a primary pathway to achieving high-quality economic growth. This paper embarks on a theoretical exploration of the profound impact of big data and blockchain technology within the sports industry, examining their current applications and potential. The research presented here seeks to unravel the intricate mechanisms through which big data and blockchain technology drive high-quality development within the sports sector's digital economy. By shedding light on these dynamics, this paper contributes valuable insights to guide and optimize the future of China's economic development, with a strong emphasis on the sports industry as a critical focal point for innovation and growth.(AU)

The Effects of Ontario Menu Labelling Regulations on Nutritional Quality of Chain Restaurant Menu Items-Cross-Sectional Examination.

Restaurant foods are associated with excessive energy intake and poor nutritional quality. In 2017, the Healthy Menu Choices Act mandated food service establishments with ≥20 outlets in Ontario to display the energy content on menus. To examine the potential impact of menu labelling, nutrition information for 18,760 menu items were collected from 88 regulated and 53 unregulated restaurants. Descriptive statistics were calculated for serving size, energy, saturated fat, sodium and total sugars. Quantile regression was used to determine the differences between regulated and unregulated restaurants. The energy content of menu items from regulated restaurants (median (95% CI): 320 kcal (310, 320)) was significantly lower than those from unregulated restaurants (470 kcal (460, 486), p < 0.001). Saturated fat, sodium and total sugars were significantly lower in regulated restaurants (4 g (4, 4), 480 mg (470, 490) and 7 g (6, 7), respectively) than in unregulated restaurants (6 g (6, 6), 830 mg (797, 862) and 8 g (8, 9), respectively, p < 0.001). This study showed that menu items from regulated restaurants had smaller serving size, lower levels of energy and nutrients of public health concern compared to those from the unregulated restaurants, suggesting potential downstream beneficial effects of menu labelling in lowering caloric content and nutrients of public health concern in foods.

Plant cadmium resistance 10 enhances tolerance to toxic heavy metals in poplar.

Toxic heavy metals originating from human activities have caused irreversible harm to the environment. Toxic heavy metal ions absorbed by crop plants can seriously threaten human health. Therefore, decreasing heavy metal contents in crop plants is an urgent need. The plant cadmium resistance protein (PCR) is a heavy metal ion transporter. In this study, PePCR10 was cloned from Populus euphratica. Bioinformatics analyses revealed its transmembrane structure and gene sequence motifs. The transcript profile of PePCR10 was analyzed by RT-qPCR, and its transcript levels increased under toxic heavy metal (cadmium, lead, aluminum) treatments. Subcellular localization analyses in tobacco cells revealed that PePCR10 localizes at the plasma membrane. Compared with wild type (WT), PePCR10-overexpressing lines showed significantly higher values for plant height, root length, fresh weight, and dry weight under heavy metal stress. Electrolyte leakage, nitroblue tetrazolium staining, and chlorophyll fluorescence analyses indicated that Cd/Al tolerance in PePCR10-overexpressing lines was stronger than that in WT. The Cd/Al contents were lower in the PePCR10-overexpressing lines than in WT under Cd/Al stress. Our results show that PePCR10 can reduce the heavy metal content in poplar and enhance its Cd/Al tolerance. Hence, PePCR10 is a candidate genetic resource for effectively reducing heavy metal accumulation in crops.

Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy.

One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1ß. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.

Jdp2 is a spatiotemporal transcriptional activator of the AhR via the Nrf2 gene battery.

BACKGROUND: Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the "AhR-Nrf2 gene battery", which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood. METHODS: Knockdown and forced expression of AhR-Nrf2 battery members were used to examine the molecular interactions between the AhR-Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR-Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR-Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors. RESULTS: Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR-Jdp2-Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells. CONCLUSIONS: Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.

Estimating Canadian sodium intakes and the health impact of meeting national and WHO recommended sodium intake levels: A macrosimulation modelling study.

BACKGROUND: Cardiovascular diseases (CVDs) are the second leading cause of total deaths in Canada. High blood pressure is the main metabolic risk factor for developing CVDs. It has been well established that excess consumption of sodium adversely affects blood pressure. Canadians' mean sodium intakes are well above recommended levels. Reducing dietary sodium intake through food reformulation has been identified as a cost-effective intervention, however, dietary sodium intake and the potential health impact of meeting recommended sodium intake levels due to food reformulation have not been determined in Canada. OBJECTIVE: This study aimed to 1) obtain robust estimates of Canadians' usual sodium intakes, 2) model sodium intakes had foods been reformulated to align with Health Canada's sodium reduction targets, and 3) estimate the number of CVD deaths that could be averted or delayed if Canadian adults were to reduce their mean sodium intake to recommended levels under three scenarios: A) 2,300 mg/d-driven by a reduction of sodium levels in packaged foods to meet Health Canada targets (reformulation); B) 2,000 mg/d to meet the World Health Organization (WHO) recommendation; and C) 1,500 mg/d to meet the Adequate Intake recommendation. METHODS: Foods in the University of Toronto's Food Label Information Program 2017, a Canadian branded food composition database, were linked to nationally representative food intake data from the 2015 Canadian Community Health Survey-Nutrition to estimate sodium intakes (and intakes had Health Canada's reformulation strategy been fully implemented). The Preventable Risk Integrated ModEl (PRIME) was used to estimate potential health impact. RESULTS: Overall, mean sodium intake was 2758 mg/day, varying by age and sex group. Based on 'reformulation' scenario A, mean sodium intakes were reduced by 459 mg/day, to 2299 mg/day. Reducing Canadians' sodium intake to recommended levels under scenarios A, B and C could have averted or delayed 2,176 (95% UI 869-3,687), 3,252 (95% UI 1,380-5,321), and 5,296 (95% UI 2,190-8,311) deaths due to CVDs, respectively, mainly from ischaemic heart disease, stroke, and hypertensive disease. This represents 3.7%, 5.6%, and 9.1%, respectively, of the total number of CVDs deaths observed in Canada in 2019. CONCLUSION: Results suggest that reducing sodium intake to recommended levels could prevent or postpone a substantial number of CVD deaths in Canada. Reduced sodium intakes could be achieved through reformulation of the Canadian food supply. However, it will require higher compliance from the food industry to achieve Health Canada's voluntary benchmark sodium reduction targets.

New potential transporter CIPAS8 enhances cadmium hypersensitivity and cobalt tolerance.

KEY MESSAGE: CIPAS8 is a novel Cd-influx and Co-efflux transporters, and Ser86 and Cys128 might play a decisive role in Co-binding and translocation. Cadmium (Cd) is among the most toxic heavy metals and is a widespread environmental pollutant. Cobalt (Co) is a mineral nutrient that is essential for plant growth and development, but high concentrations may be toxic. Cadmium-induced protein AS8 (CIPAS8) is widely distributed among plant species and might be induced by heavy metals, but its function has not been studied previously. In this study, Populus euphratica PeCIPAS8 and Salix linearistipularis SlCIPAS8 were investigated. The transcription of both genes was significantly enhanced under Cd and Co stresses. PeCIPAS8 and SlCIPAS8 conferred sensitivity to Cd in transgenic yeast, allowing higher quantities of Cd to accumulate within the cells, whereas SlCIPAS8 also conferred tolerance to Co and reduced Co accumulation. The determinants of substrate selectivity of the SlCIPAS8 protein were examined by site mutagenesis, which indicated that the Ser at 86th (S86) substituted for Arg (R) [S86R] and Cys at 128th (C128) substituted for Ser [C128S] mutations limited the protein's capability for Co translocation. These results suggested that PeCIPAS8 and SlCIPAS8 may be involved in Cd uptake into the plant cell. SlCIPAS8 can reduce excess Co accumulation to maintain intracellular Co homeostasis, and the site mutations S86R and C128S were essential for Co transport. These findings provide insight into the function of CIPAS8 and highlight its potential for utilization in phytoremediation applications.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.