Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice.

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aß fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.

Overexpression of the FERONIA receptor kinase MdMRLK2 enhances apple cold tolerance.

Cold is one of the main abiotic stresses in temperate fruit crops, affecting the yield and fruit quality of apple in China and European countries. The plant receptor-like kinase FERONIA is widely reported to be involved in abiotic stresses. However, its function in apple cold resistance remains unknown. Modification of cell wall components and accumulation of soluble sugars and amino acids are important strategies by which plants cope with cold. In this study, expression of the apple FERONIA receptor-like kinase gene MdMRLK2 was rapidly induced by cold. Apple plants overexpressing MdMRLK2 (35S:MdMRLK2) showed enhanced cold resistance relative to the wild type. Under cold conditions, 35S:MdMRLK2 apple plants had higher amounts of water insoluble pectin, lignin, cellulose, and hemicellulose, which may have resulted from reduced activities of polygalacturonase, pectinate lyase, pectinesterase, and cellulase. More soluble sugars and free amino acids and less photosystem damage were also observed in 35S:MdMRLK2 apple plants. Intriguingly, MdMRLK2 interacted with the transcription factor MdMYBPA1 and promoted its binding to MdANS and MdUFGT promoters, leading to more anthocyanin biosynthesis, particularly under cold conditions. These findings complemented the function of apple FERONIA MdMRLK2 responding to cold resistance.

Correlation between triglyceride glucose-body mass index and hypertension risk: evidence from a cross-sectional study with 60,283 adults in eastern China.

BACKGROUND: Insulin resistance (IR) and obesity are established risk factors for hypertension, with triglyceride-glucose (TyG) serving as a recognized surrogate marker for IR. The aim of this study was to investigate the association between TyG-BMI and hypertension in the general population. METHODS: A total of 60,283 adults aged ≥18 years who underwent face-to-face questionnaires, anthropometric measurements, and laboratory examination were included in this study. Multivariable logistic regression models and receiver operating characteristic curve (ROC) were used to determine the association between TyG-BMI and hypertension. The restricted cubic spline model was used for the dose-response analysis. RESULTS: After fully adjusting for confounding variables, multivariate logistic regression model showed a stable positive association between TyG-BMI and hypertension (OR: 1.61 per SD increase; 95% CI: 1.55-1.67; P-trend < 0.001). The multivariate adjusted OR and 95% CI for the highest TyG-BMI quartile compared with the lowest quartile were 2.52 (95% CI 2.28-2.78). Dose-response analysis using restricted cubic spline confirmed that the association between TyG-BMI index and hypertension was linear. Subgroup analyses showed that stronger associations between TyG-BMI index and hypertension were detected in young and middle-aged individuals (P for interaction < 0.05). ROC analysis showed that TyG-BMI index could better predict the risk of hypertension than other parameters (TyG-BMI cut-off value: 207.105, AUC: 0.719, sensitivity 65.5%, specificity 66.8%), particularly among young and middle-aged people. CONCLUSION: The TyG-BMI index was independently associated with hypertension in the study population. Further studies are required to confirm this relationship.

Anomalous Nernst Effect Induced Terahertz Emission in a Single Ferromagnetic Film.

Despite its important role in understanding ultrafast spin dynamics and revealing novel spin/orbit effects, the mechanism of the terahertz (THz) emission from a single ferromagnetic nanofilm upon a femtosecond laser pump still remains elusive. Recent experiments have shown exotic symmetry, which is not expected from the routinely adopted mechanism of ultrafast demagnetization. Here, by developing a bidirectional pump-THz emission spectroscopy and associated symmetry analysis method, we set a benchmark for the experimental distinction of the THz emission induced by various mechanisms. Our results unambiguously unveil a new mechanism─anomalous Nernst effect (ANE) induced THz emission due to the ultrafast temperature gradient created by a femtosecond laser. Quantitative analysis shows that the THz emission exhibits interesting thickness dependence where different mechanisms dominate at different thickness ranges. Our work not only clarifies the origin of the ferromagnetic-based THz emission but also offers a fertile platform for investigating the ultrafast optomagnetism and THz spintronics.

Ref-MEF: Reference-Guided Flexible Gated Image Reconstruction Network for Multi-Exposure Image Fusion.

Multi-exposure image fusion (MEF) is a computational approach that amalgamates multiple images, each captured at varying exposure levels, into a singular, high-quality image that faithfully encapsulates the visual information from all the contributing images. Deep learning-based MEF methodologies often confront obstacles due to the inherent inflexibilities of neural network structures, presenting difficulties in dynamically handling an unpredictable amount of exposure inputs. In response to this challenge, we introduce Ref-MEF, a method for color image multi-exposure fusion guided by a reference image designed to deal with an uncertain amount of inputs. We establish a reference-guided exposure correction (REC) module based on channel attention and spatial attention, which can correct input features and enhance pre-extraction features. The exposure-guided feature fusion (EGFF) module combines original image information and uses Gaussian filter weights for feature fusion while keeping the feature dimensions constant. The image reconstruction is completed through a gated context aggregation network (GCAN) and global residual learning GRL. Our refined loss function incorporates gradient fidelity, producing high dynamic range images that are rich in detail and demonstrate superior visual quality. In evaluation metrics focused on image features, our method exhibits significant superiority and leads in holistic assessments as well. It is worth emphasizing that as the number of input images increases, our algorithm exhibits notable computational efficiency.

Targeting ER stress/PKA/GSK-3ß/ß-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/ß-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/ß-catenin signaling is needed. METHODS: Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection. RESULTS: Both chronic HCV infection and replicon-induced Wnt/ß-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3ß-mediated Wnt/ß-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3ß-mediated Wnt/ß-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection. CONCLUSION: Targeting ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/ß-catenin signaling by DAA treatment. Video Abstract.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Effects of overexpression of Hsp70 in neural stem cells on neurotoxicity and cognitive dysfunction in neonatal mice under sevoflurane exposure.

As one of the commonly used inhalation anesthetics in clinical practice, sevoflurane is currently widely applied in surgery for children and the elderly due to its safety and efficacy. However, the neurotoxicity and cognitive impairment induced by sevoflurane exposure cannot be ignored. A recombinant adenovirus with green fluorescent protein-labeled heat shock protein 70 (Hsp70) was constructed and used to infect neural stem cells (NSCs) separated from neonatal mice. Quantitative real-time PCR and Western blot assays were used to evaluate the expression of certain genes. 5­Ethynyl­2'­deoxyuridine staining and cell counting kit assay were used to detect the proliferation and differentiation ability of NSCs. The Morris water maze experiment was used to test the cognitive abilities of mice. Adv-Hsp70 induced the overexpression of Hsp70 in mouse NSCs. Upregulation of Hsp70 promoted the proliferation ability and differentiation of mouse NSCs. NSCs that overexpressed Hsp70 attenuated sevoflurane-induced neurotoxicity and protected cognitive dysfunction in mice under sevoflurane exposure. In summary, our findings demonstrate the potential of overexpression of Hsp70 in NSCs against sevoflurane-induced impairments.

Fresh fruit consumption, physical activity, and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study.

BACKGROUND AND AIMS: We explored the associations among fruit consumption, physical activity, and their dose-response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. METHODS AND RESULTS: We prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21-94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose-response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64-0.88), CVD mortality (HR 0.69, 0.51-0.94) and stroke mortality (HR 0.57, 0.36-0.89), but not with heart disease mortality (HR 0.93, 0.56-1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37-0.53) for all-cause mortality, 0.46 (0.33-0.64) for CVD mortality, 0.46 (0.29-0.74) for stroke mortality and 0.51 (0.29-0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. CONCLUSIONS: Fruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.

Simultaneous bilateral fallopian tubal pregnancy of a laparoscopic definite spontaneous unilateral ovulation: a case report.

BACKGROUND: Bilateral simultaneous fallopian tubal pregnancy is one of the rarest forms of ectopic pregnancy. Due to the lack of unique features and clinical presentation to distinguish bilateral from unilateral ectopic pregnancy, challenges the diagnosis. CASE REPORT: A 27-year-old Asian woman presented with pelvic pain and vaginal bleeding. Pelvic transvaginal ultrasound showed fluid in Douglas Pouch and posterior fornix puncture revealed unclotted blood. Laparoscopic examination unveiled bilateral ectopic pregnancy with two corpus luteum visible in the right ovary, suggesting a double spontaneous unilateral ovulation. Bilateral fallopian tube fenestration and embryo extraction were performed to preserve fertility. CONCLUSION: Diagnosis of bilateral tubal pregnancy is difficult during preoperative ultrasound examination and careful examination during laparoscopic inspection of the whole pelvic cavity to avoid missed diagnosis.

JNK1/ß-catenin axis regulates H2O2-induced epithelial-to-mesenchymal transition in human lens epithelial cells.

Epithelial-mesenchymal transition (EMT) is the main cause of fibrotic cataracts. Oxidative stress was recently shown to trigger epithelial-mesenchymal transition in human lens epithelial cells (hLECs). However, the underlying mechanism is not fully understood. Here we reported that exposure to low doses (100 µM) of H2O2 led to EMT in hLECs, as indicated by simultaneous down-regulated of E-cadherin and ZO-1, and up-regulated of alpha smooth muscle actin (α-SMA). H2O2-induced EMT was accompanied by accumulation of phosphorylated JNK1. In contrast, knockdown of JNK1 via siRNA reversed H2O2-induced EMT. Of interest, in human lens capsules of anterior subcapsule cataracts, the expressions of JNK1, as well as ß-catenin and its downstream effectors cyclin D and c-Myc, were augmented compared to that in normal lens capsules. Mechanistically, activated JNK1 dislodged ß-catenin from the cell membrane, which subsequently translocated to the nuclei and triggered transcription of its effectors. Nuclei ß-catenin, cyclin D and c-Myc were accumulated in H2O2-induced EMT and JNK1 depletion abrogated these trend in hLECs. In conclusion, our data suggest that JNK1 is essential for H2O2-induced EMT in hLECs via mediating the translocation of ß-catenin.

Absence of the Thermal Hall Effect in Anomalous Nernst and Spin Seebeck Effects.

The anomalous Nernst effect (ANE) and the spin Seebeck effect (SSE) in spin caloritronics are two of the most important mechanisms to manipulate the spin-polarized current and pure spin current by thermal excitation. While the ANE in ferromagnetic metals and the SSE in magnetic insulators have been extensively studied, a recent theoretical work suggests that the signals from the thermal Hall effect (THE) have field dependences indistinguishable from, and may even overwhelm, those of the ANE and SSE. Therefore, it is vital to investigate the contribution of the THE in the ANE and SSE. In this work, we systematically study the THE in a ferromagnetic metal, Permalloy (Py), and magnetic insulator, an yttrium iron garnet (YIG), by using different Seebeck coefficients between electrodes and contact wires. Our results demonstrate that the contribution of the THE by the thermal couple effect in the Py and YIG is negligibly small if one includes the thickness dependence of the Seebeck coefficient. Thus, the spin-polarized current in the ANE and the pure spin current in the SSE remain indispensable for exploring spin caloritronics phenomena.

Melatonin Ameliorates Sevoflurane Anesthesia-Induced Deficits in Learning and Memory of Aged Mice Through Nrf2 Signaling Related Ferroptosis.

Our research aimed at investigating the protective effects in aged mice exposed to sevoflurane anesthesia. To assess learning and memory abilities and exploratory behavior, the novel object recognition (NOR) test, Morris water maze (MWM) test, and open field test were employed. Commercial kits were used to measure levels of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase activity, superoxide dismutase activity, catalase activity, and iron. The messenger RNA and protein levels of ferritin heavy chain 1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and glutathione peroxidase 4 in the hippocampus were detected. Treatment with melatonin significantly ameliorated the decrease in exploration time of novel objects and the discrimination index induced by sevoflurane anesthesia. Melatonin also reduced escape latencies and increased the time spent in the target quadrant in the MWM test. In the open field test, melatonin-treated mice exhibited greater exploratory activity, including longer distances traveled and a higher number of rearing events. Further, melatonin treatment markedly decreased the levels of oxidative stress markers and iron in the hippocampus of aged mice exposed to sevoflurane anesthesia. However, the beneficial effects of melatonin were significantly attenuated following treatment with the Nrf2 inhibitor ML385. Our results suggest that melatonin could alleviate learning and memory impairment induced by sevoflurane anesthesia in aged mice through its antioxidant properties, partially through the Nrf2 pathway.

The relationship between social media usage and loneliness among younger and older adults: the moderating effect of shyness.

Does social media alleviate or exacerbate loneliness? Past research has shown mixed results regarding the relationship between social media usage and loneliness among younger and older adults. Unlike younger individuals, older adults may decrease their loneliness through social media interactions. Additionally, previous research has indicated that the link between social media use and loneliness can vary depending on one's shy tendency. Therefore, this study aims to explore the relationship between individuals' social media use and loneliness while considering age and shyness tendency as moderating variables. The study employed a questionnaire survey conducted through convenience sampling, resulting in 234 valid responses from participants in Northern Taiwan. Among them, 113 were college students (aged 18 to 25, average age 19.40), and 121 were older adults (aged 50 to 82, average age 60.81). Using hierarchical regression analysis, results indicated that (1) age moderates the relationship between personal social media use and loneliness. Minimal differences were observed among younger individuals, but among older adults, increased social media usage time was associated with a significant reduction in loneliness. (2) Shyness tendency moderate the relationship between personal social media use and loneliness. Individuals with higher shyness tendency experience an increase in loneliness as their social media usage time lengthens.

The association between alcohol drinking and glycemic management among people with type 2 diabetes in China.

INTRODUCTION: To investigate the association between alcohol drinking and glycemic management among adult patients with type 2 diabetes in regional China. MATERIALS AND METHODS: In this cross-sectional survey conducted in Nanjing Municipality of China in 2018, adult type 2 diabetes patients were randomly selected from urban and rural communities. The outcome variable was the glycemic management status. The explanatory measure was alcohol drinking. Mixed-effects regression models were employed to estimate odds ratios (ORs) and 95% confidence interval (95% CI) for examining the associations of alcohol drinking with glycemic management among type 2 diabetes patients. RESULTS: Among the overall 5,663 participants, the glycemic management rate was 39.8% (95% CI = 38.5, 41.1), with 41.2% (95% CI = 39.7, 42.7), 43.9% (95% CI = 38.9, 48.8), and 34.1% (95% CI = 31.5, 36.7) for non-drinkers, mild/moderate drinkers, and heavy drinkers, respectively. After adjustment for potential confounders and community-level clustering effect, heavy and mild/moderate alcohol drinkers were at 0.76 (95% CI = 0.66, 0.89) and 1.04 (95% CI = 0.87, 1.28) times odds to have glycemia under control than non-drinkers among the overall participants. Furthermore, when stratified separately by gender and use of anti-diabetes agents, the scenario within men, either regular or irregular users of anti-diabetes agents was the same as that for overall participants, while the association between alcohol drinking and glycemic management became non-significant among women. CONCLUSIONS: Heavy alcohol drinking might have a negative effect on glycemic management among patients with type 2 diabetes irrespective of the use of anti-diabetes agents in regional China. This study has important public health implications regarding precision intervention on patients' glycemia control for type 2 diabetes management.

Uterine Burkitt Lymphoma with Rare Extranodal Deposits in the Bone, Breast, and Sacral Canal: A Case Report.

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.

Sustaining Healthy Habits: The Enduring Impact of Combined School-Family Interventions on Consuming Sugar-Sweetened Beverages among Pilot Chinese Schoolchildren.

This study assesses the enduring impact of combined school- and family-based interventions on reducing the consumption of sugar-sweetened beverages (SSBs) among schoolchildren in China. Two primary schools were assigned at random to either the Intervention Group or the Control Group, in Nanjing, eastern China. All students were in grade three and received an invitation to participate. In the first year, students in the Intervention Group received one-year intervention measures, including monthly monitoring, aiming to decrease the consumption of SSBs. Students in the Control Group only received regular monitoring without interventions. In the second year, both groups received only regular monitoring, without active interventions. A generalized estimating equations model (GEE) was used to assess the intervention effects. After two years, relative to the Control Group, the Intervention Group had a significantly improved knowledge of SSBs and an improved family environment with parents. In the Intervention Group, 477 students (97.3%) had adequate knowledge about SSBs, compared to 302 students (83.2%) in the Control Group (X2 = 52.708, p < 0.001). Two years later, the number of students who stated 'my home always has SSBs' in the Intervention Group (7.8%) was fewer than that in the Control Group (12.4%), which was a statistically significant finding (p < 0.05). One year later, both the frequency and the quantity of SSB consumption in the Intervention Group were less than those in the Control Group; such differences between the groups remained statistically significant for the quantity but not for the frequency of SSB consumption two years later. In the Intervention Group, the frequency of SSB consumption was significantly reduced by 1.0 times per week, compared to a reduction of 0.1 times per week in the Control Group in the first year (p < 0.05). In the second year, the frequency of SSB consumption was reduced by 0.8 times per week in the Intervention Group, compared to 0.5 times per week in the Control Group (p > 0.05). In the first year, the volume of SSB consumption was significantly reduced by 233 mL per week in the Intervention Group, compared to an increase of 107 mL per week in the Control Group (p < 0.05). In the second year, the volume of SSB consumption was reduced by 122 mL per week in the Intervention Group compared to an increase of 31 mL per week in the Control Group (p > 0.05). The combined school-based and family-based interventions had a positive effect on the students' knowledge of SSBs and their family dynamics during the first and second year. Relative to the Control Group, the Intervention Group had a statistically significant reduction in SSB consumption after 1 year, but not after 2 years.

Tryptophan deficiency induced by indoleamine 2,3-dioxygenase 1 results in glucose transporter 1-dependent promotion of aerobic glycolysis in pancreatic cancer.

Indoleamine 2,3-dioxygenase 1 (IDO1), the key enzyme in the catabolism of the essential amino acid tryptophan (Trp) through kynurenine pathway, induces immune tolerance and is considered as a critical immune checkpoint, but its impacts as a metabolism enzyme on glucose and lipid metabolism are overlooked. We aim to clarify the potential role of IDO1 in aerobic glycolysis in pancreatic cancer (PC). Analysis of database revealed the positive correlation in PC between the expressions of IDO1 and genes encoding important glycolytic enzyme hexokinase 2 (HK2), pyruvate kinase (PK), lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1). It was found that IDO1 could modulate glycolysis and glucose uptake in PC cells, Trp deficiency caused by IDO1 overexpression enhanced glucose uptake by stimulating GLUT1 translocation to the plasma membrane of PC cells. Besides, Trp deficiency caused by IDO1 overexpression suppressed the apoptosis of PC cells via promoting glycolysis, which reveals the presence of IDO1-glycolysis-apoptosis axis in PC. IDO1 inhibitors could inhibit glycolysis, promote apoptosis, and exhibit robust therapeutic efficacy when combined with GLUT1 inhibitor in PC mice. Our study reveals the function of IDO1 in the glucose metabolism of PC and provides new insights into the therapeutic strategy for PC.

TRIM38 Induced in Respiratory Syncytial Virus-infected Cells Downregulates Type I Interferon Expression by Competing with TRIM25 to Bind RIG-I.

Innate immune response is the first line of defense for the host against virus invasion. One important response is the synthesis and secretion of type I interferon (IFN-I) in the virus-infected host cells. Here, we found that respiratory syncytial virus (RSV) infection induced high expression of TRIM25, which belongs to the tripartite motif-containing (TRIM) family of proteins. TRIM25 bound and activated retinoic acid-inducible gene I (RIG-I) by K63-linked ubiquitination. Accordingly, RIG-I mediated the production of IFN-I mainly through the nuclear factor kappa-B (NF-κB) pathway in respiratory epithelial cells. Interestingly, IFN-I, in turn, promoted a high expression of TRIM38 which downregulated the expression of IFN-I by reducing the protein level of RIG-I by K48-linked ubiquitination. More importantly, the binding site of TRIM25 to RIG-I was found in the narrow 25th-43rd amino acid (aa) region of RIG-I N-terminus. In contrast, the binding sites of TRIM38 to RIG-I were found in a much wider amino acid region, which included the binding site of TRIM25 on RIG-I. As a result, TRIM38 inhibits the production of IFN-I by competing with TRIM25 for RIG-I binding. Thus, TRIM38 negatively regulates RIG-I activation to, in turn, downregulate IFN-I expression, thus interfering with host immune response. A negative feedback loop effectively "puts the brakes" on the reaction once host immune response is overactivated and homeostasis is unbalanced. We also discovered that TRIM25 bound RIG-I by a new K63-linked ubiquitination located at K-45 of the first caspase recruitment domain (CARD). Collectively, these results confirm an antagonism between TRIM38 and TRIM25 in regulating IFN-I production by affecting RIG-I activity following RNA virus infection.

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation.