Association between breakfast patterns and executive function among adolescents in Shanghai, China.

Introduction: The aim of this cross-sectional study was to investigate the association between breakfast patterns and executive function among adolescents in Shanghai, China. Methods: In 2022, we randomly recruited 3,012 adolescents aged 12-13 years from all administrative districts in Shanghai. Breakfast information was collected by parents using a one-day recall method. Executive function was measured using the Behavior Rating Inventory of Executive Function-Parent Version. Latent Class Analysis was performed to identify breakfast patterns based on the food groups in the Diet Quality Questionnaire for China. Results: Breakfast patterns were classified into three categories: "Egg and milk foods", "Grain foods", and "Abundant foods", except for adolescents who skipped breakfast. Logistic regression was used to estimate the multivariate odds ratio (ORs) and 95% confidence intervals (95% CI) for the association between breakfast patterns and potential executive dysfunction. Adolescents in the "Abundant foods" class had a lower risk of executive dysfunction in terms of initiate (OR: 0.36; 95% CI: 0.17-0.76), and organization of materials (OR: 0.18; 95% CI: 0.04-0.94), compared to those who skipped breakfast. Similarly, the breakfast patterns of "Grain foods" and "Egg and milk foods" were associated with a lower risk of executive dysfunction, including initiate and working memory. Discussion: Our findings suggest that breakfast patterns were associated with executive function. The improvement of breakfast patterns among adolescents should be a significant public health intervention.

Phenotypic and genotypic characterization of NPRL3-related epilepsy: Two case reports and literature review.

Nitrogen permease regulator-like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3-related epilepsy is a range of epilepsy-associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3-related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C > T, p.Gln392*) and a missense variant (c.1322C > T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3-related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the existence of NPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3-related epilepsy. PLAIN LANGUAGE SUMMARY: This study expands the phenotypic and genotypic spectra of NPRL3-related epilepsy by reporting two cases with different novel variants. Following a review of the literature, it was observed that patients harboring various NPRL3 variants exhibited a variability of clinical manifestations. Also, patients carrying nonsense mutations are frequently prone to drug resistance and other severe comorbidities such as developmental delay, but more cases need to be collected to confirm these findings.

The Relationship Between Prognostic Nutritional Indexes and the Clinical Outcomes of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Nutritional status is related to the clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to investigate the association between nutritional status, measured by the prognostic nutritional index (PNI), and adverse hospitalization outcomes in patients with AECOPD. Methods: Consecutive AECOPD patients admitted to the First Affiliated Hospital of Sun Yat-sen University between January 1, 2015 to October 31, 2021 were enrolled. We collected the clinical characteristics and laboratory data of patients. Multivariable logistic regression models were developed to assess the relationship between the baseline PNI and adverse hospitalization outcomes. A generalized additive model (GAM) was used to identify any non-linear relationship. In addition, we performed a subgroup analysis to tested the robustness of the results. Results: A total of 385 AECOPD patients were involved in this retrospective cohort study. Based on the tertiles of PNI, patients in the lower tertiles of PNI showed more worse outcome incidence (30 [23.6%] versus 17 [13.2%] versus 8 [6.2%]; p < 0.001). Multivariable logistic regression analysis revealed that the PNI were independently associated with adverse hospitalization outcomes after adjustment for confounding factors (Odds ratio [OR] = 0.94, 95% CI: 0.91 to 0.97, P < 0.0001). After adjusting for confounders, smooth curve fitting showed a saturation effect, suggesting that the relationship between the PNI and adverse hospitalization outcomes was nonlinear. Two-piecewise linear regression model suggested that the incidence of adverse hospitalization outcomes significantly decreased with PNI level up to the inflection point (PNI = 42), and PNI was not associated with adverse hospitalization outcome after that point. Conclusion: Decreased PNI levels at admission were determined to be associated with adverse hospitalization outcomes in patients with AECOPD. The results obtained in this study may potentially assist clinicians optimize risk evaluations and clinical management processes.

Association of health-risk behaviors with perceived academic performance among middle and high school students: A cross-sectional study in Shanghai, China.

Adolescence is a susceptible period to establish health-risk behaviors, which may have an impact on academic performance. The aim of this study was to investigate the association between health-risk behaviors (HRBs) and perceived academic performance (PAP) of adolescents in Shanghai, China. The data of the present study included three-round Shanghai Youth Health-risk Behavior Survey (SYHBS). This cross-sectional survey investigated multiple HRBs of students involved in dietary behaviors, physical activity and sedentary behaviors, intentional and unintentional injury behaviors, and substance abuse behaviors, as well as PAP by using self-reported questionnaire. Using a multistage random sampling method, 40,593 middle and high school students aged 12 to 18 years were involved. Only participants with complete data on HRBs information, academic performance and covariates were included. A total of 35,740 participants were involved in analysis. We used ordinal logistic regression to analyze the association between each HRB and PAP adjusting for sociodemographic, family environment and duration of extracurricular study. The results showed that students who did not eat breakfast or drink milk everyday were more likely to have a lower PAP, with a decreased odds of 0.89 (95%CI: 0.86-0.93, P<0.001) and 0.82 (95%CI: 0.79-0.85, P<0.001), respectively. The similar association was also found in students who did exercise ≥60 minutes for less than 5 days/week, spend time on watch TV beyond 3 hours/day and other sedentary behaviors. Most intentional and unintentional injuries, and ever smoked were associated with a lower PAP. Our finding suggests that multiple HRBs negatively associated with PAP of adolescents. It needs to raise public health concerns with HRBs in adolescents, and to develop and implement comprehensive interventions on HRBs.

Safety and efficacy of gene therapy with onasemnogene abeparvovec in the treatment of spinal muscular atrophy: A systematic review and meta-analysis.

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease which leads to progressive muscle weakness and atrophy. Our systematic review and meta-analysis aims to explore the efficacy and safety of onasemnogene abeparvovec in SMA patients. We searched PubMed, EMBASE, Web of Science and Cochrane through April 2022. Ten reports enrolling 250 SMA patients were included. CHOP INTEND and motor-milestone significant improvements were detected at both short- and long-term follow-up. Common adverse events included pyrexia, vomiting, thrombocytopenia and elevated aminotransferases. Thrombocytopenia (79.3%, 95%CI: 65.8~90.5) and elevated aminotransferases (71.7%, 95%CI: 62.5~80.1) were more common in SMA patients aged older than 8 months. Despite the paucity of randomized control trial data and low quality of evidence to establish the safety and efficacy of onasemnogene abeparvovec in the treatment of SMA, the data suggest that it is a valuable option for patients with this condition.

Maize-soybean intercropping facilitates chemical and microbial transformations of phosphorus fractions in a calcareous soil.

Intercropping often substantially increases phosphorus (P) availability to plants compared with monocropping, which could be an effective strategy for soil legacy P recovery and agricultural production. However, the biogeochemical interactions among plants, microbes, and soil that mobilize P remain largely unknown in intercropping systems. Pot experiments with maize-soybean intercropping in a calcareous soil were conducted to investigate the potential chemical and biological transformation mechanisms of inorganic P (Pi) and organic P (Po) using sequential extraction and Illumina MiSeq sequencing. Compared to monocropping of each crop, maize-soybean intercropping significantly enhanced total P uptake of the two crops by mobilizing Ca2-Pi [extracted by bicarbonate (NaHCO3)], Al-Pi/Po [extracted by ammonium fluoride (NH4F)] and Fe-Pi [extracted by sodium hydroxide and sodium carbonate (NaOH-Na2CO3)] fractions. Furthermore, there were significant increases in the organic carbon content and alkaline phosphomonoesterase (ALP) and phosphodiesterase (PDE) activities as well as the abundances of Microvirga, Lysobacter, Microlunatus and Sphingomonas under maize-soybean intercropping relative to monocropping. In contrast, compared to monocroppping, no significant change in the soil pH was observed under maize-soybean intercropping. Therefore, the enhanced P uptake of the maize-soybean intercropping probably resulted from a synergistic effect of rhizosphere organic carbon deposit, increased activities of ALP and PDE, together with the bacteria (Microvirga, Lysobacter, Microlunatus and Sphingomonas) which showed correlation with soil P forms, while the generally recognized rhizosphere acidification was excluded in this investigated calcareous soil. Moreover, the selected bacterial genera exhibited a closer network in the rhizosphere of soybean compared to maize, suggesting enhanced interactions among bacteria in the soybean rhizosphere. These results provide theoretical bases for the recovery of soil legacy P by maize-soybean intercropping.

Recent research on the treatment of spinal muscular atrophy. / è„Šé«“æ€§è‚ŒèŽç¼©ç—‡æ²»ç–—ç ”ç©¶è¿›å±•.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy. SMA, as an inherited disease, is the leading cause of death in infants and young children. Rapid progress has been made in the research field of SMA in recent years, and some related treatment drugs have been successfully approved for marketing. This article reviews the recent research advances in the treatment of SMA.

Changes in obesity and lifestyle behaviours during the COVID-19 pandemic in Chinese adolescents: A longitudinal analysis from 2019 to 2020.

BACKGROUND: Since December 2019, the coronavirus disease 2019 (COVID-19) has become a global pandemic. Currently, the COVID-19 pandemic is still ongoing. What changes have taken place in the obesity and obesity-related lifestyle behaviours of adolescents during the first year of the COVID-19 pandemic? OBJECTIVE: This study aims at analysing the changes in obesity and lifestyle behaviours of Chinese adolescents before and 1 year after the outbreak of the COVID-19 pandemic, providing evidence for the global strategies to respond to the impact of the COVID-19 pandemic on adolescent obesity. METHODS: Physical examinations and student health and influencing factors questionnaires were conducted among 6047 adolescents aged 11-16 years by health professionals in Shanghai, China, before the COVID-19 pandemic (September-November of 2019) and 1 year after the outbreak of the COVID-19 pandemic (September-November of 2020). Paired χ2 tests, paired t-tests or Wilcoxon signed-rank test was used to evaluate the changes in the obesity prevalence, BMI and lifestyle behaviours from 2019 to 2020. RESULTS: 1 year after the outbreak of the COVID-19 pandemic, the obesity prevalence of Chinese adolescents rose from 14.2% to 15.4% (p < 0.01), mainly because of the increase in boys. And the average BMI increased from 20.3 to 21.2 kg/m2 (p < 0.01). Their lifestyle behaviours have also significantly changed. The mobile screen time increased from 0.25-1.50 h/day to 0.33-2.00 h/day (p < 0.01). The proportion of adolescents who participated in MVPA for ≥60 min/day on all 7 days during the past week dropped from 14.4% to 11.7% (p < 0.01). The generalized estimation equation analysis indicated that adolescents who participated in MVPA for ≥60 min/day on all 7 days had a lower likelihood of having obesity. Boys with computer time ≥2 h/day and girls with mobile screen time ≥2 h/day or TV time ≥2 h/day had a higher likelihood of having obesity. CONCLUSION: This study found that 1 year after the outbreak of the COVID-19 pandemic, the BMI and obesity prevalence of Chinese adolescents increased and obesity-related lifestyle behaviours have also changed.

Conditioning Regimen of 5-Day Decitabine Administration for Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome and Myeloproliferative Neoplasms.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). However, post-HSCT relapse remains a major cause of treatment failure. Here we assessed the efficacy of a new conditioning regimen comprising decitabine (Dec), busulfan (Bu), cyclophosphamide (Cy), fludarabine (Flu), and cytarabine (Ara-c) for allo-HSCT in patients with MDS and MDS/MPN. A total of 48 patients were enrolled, including 44 with MDS and 4 with chronic myelomonocytic leukemia (CMML). Patients received Dec 20 mg/m2/day on days -9 to -5, combined with a Bu/Cy/Flu/Ara-c-modified preparative regimen. At a median follow-up of 522 days (range, 15 to 1313 days), the overall survival (OS) was 86%, relapse incidence was 12%, and nonrelapse mortality was 12%. The incidence of severe acute (grade III-IV) graft-versus-host disease (GVHD) was 23% and that of chronic GVHD was 15%. At 2 years, OS was 74% and 86%, respectively for high-risk and very-high-risk patients with MDS. Survival was promising in patients with poor-risk gene mutations, such as TP53 and ASXL1 (88%), and in those with ≥3 gene mutations (79%). Results of immunomonitoring studies revealed that proper natural killer cells made essential contributions to these favorable clinical outcomes. Overall, this new regimen was associated with a low relapse rate, low incidence and severity of GVHD, and satisfactory survival in allo-HSCT recipients with MDS and MDS/MPN.

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

The signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis.

The apical-basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK. We find that MCAM-mediated vesicular trafficking towards FGF4, while generating a priority-grade transcriptional response of NFAT determines lumenogenesis. We demonstrate that MCAM plays indispensable roles in ciliogenesis through activating JNK independently of FGF signals. Furthermore, mcam-deficient zebrafish and Xenopus exhibit a global defect in left-right (LR) asymmetric establishment as a result of morphogenetic failure of their LR organizers. Therefore, MCAM coordination of AB polarity and PCP provides insight into the general mechanisms of morphogenesis.

Macrophagic CD146 promotes foam cell formation and retention during atherosclerosis.

The persistence of cholesterol-engorged macrophages (foam cells) in the artery wall fuels the development of atherosclerosis. However, the mechanism that regulates the formation of macrophage foam cells and impedes their emigration out of inflamed plaques is still elusive. Here, we report that adhesion receptor CD146 controls the formation of macrophage foam cells and their retention within the plaque during atherosclerosis exacerbation. CD146 is expressed on the macrophages in human and mouse atheroma and can be upregulated by oxidized low-density lipoprotein (oxLDL). CD146 triggers macrophage activation by driving the internalization of scavenger receptor CD36 during lipid uptake. In response to oxLDL, macrophages show reduced migratory capacity toward chemokines CCL19 and CCL21; this capacity can be restored by blocking CD146. Genetic deletion of macrophagic CD146 or targeting of CD146 with an antibody result in much less complex plaques in high-fat diet-fed ApoE-/- mice by causing lipid-loaded macrophages to leave plaques. Collectively, our findings identify CD146 as a novel retention signal that traps macrophages within the artery wall, and a promising therapeutic target in atherosclerosis treatment.

A modified busulfan and cyclophosphamide preparative regimen for allogeneic transplantation in myeloid malignancies.

BACKGROUND: Busulfan/cyclophosphamide (Bu/Cy) is commonly used as a standard conditioning regimen without total body irradiation for patients with hematological myeloid malignancies undergoing hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To develop a new myeloablative conditioning regimen incorporating fludarabine (Flu) and cytarabine (Ara-c). SETTING: A tertiary blood disease hospital in Tianjin, China. METHODS: A Bu/Cy preparative regimen was used, modified by Flu 90 mg/m(2) and Ara-c 6 g/m(2) in 57 unselected patients (median age 37 years) with hematological myeloid malignancies. The patients were to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirteen patients had high-risk leukemia, fifty patients had HLA matched sibling donors while seven patients had HLA mismatched sibling donors. Cy was given 50 mg/kg/day for 2 days while Bu was given 3.2 mg/kg/day intravenously for 3 days. MAIN OUTCOME MEASURE: Post-transplant donor chimerism, relapse tendency and minimal residual disease. RESULTS: Extramedullar toxicity was relatively limited; the incidence of treatment-related mortality (TRM) within 100 days was 3.5 %. The incidence of grade II-IV, grade III-IV acute graft versus host disease (GVHD) and chronic GVHD of the evaluable patients were 21.1, 8.8 and 36.4 %, respectively. With a median follow up of 59 (13-96.5) months, TRM and relapse rate (RR) at eight years were 24.1 ± 5.8 and 14.7 ± 4.8 %, respectively. Disease free survival at eight years was 67.9 ± 6.2 % for the entire group, 60.0 ± 8.9 % for patients with AML, 77.3 ± 8.9 % for patients with CML, 70.0 ± 6.5 and 42.9 ± 18.7 % or matched sibling and mismatched sibling HSCT respectively. CONCLUSION: The new regimen was associated with a low relapse rate, low incidence and severity of graft versus host disease and satisfactory survival for patients with myeloid malignancies.

H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection.

An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery.

Impaired tumor angiogenesis and VEGF-induced pathway in endothelial CD146 knockout mice.

CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.

Quantitative proteomics reveals ER-α involvement in CD146-induced epithelial-mesenchymal transition in breast cancer cells.

The cell adhesion molecule CD146 is a novel inducer of epithelial-mesenchymal transition (EMT), which was associated with triple-negative breast cancer (TNBC). To gain insights into the complex networks that mediate CD146-induced EMT in breast cancers, we conducted a triple Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC), to analyze whole cell protein profiles of MCF-7 cells that had undergone gradual EMT upon CD146 expression from moderate to high levels. In this study, we identified 2293 proteins in total, of which 103 exhibited changes in protein abundance that correlated with CD146 expression levels, revealing extensive morphological and biochemical changes associated with EMT. Ingenuity Pathway Analysis (IPA) showed that estrogen receptor (ER) was the most significantly inhibited transcription regulator during CD146-induced EMT. Functional assays further revealed that ER-α expression was repressed in cells undergoing CD146-induced EMT, whereas re-expression of ER-α abolished their migratory and invasive behavior. Lastly, we found that ER-α mediated its effects on CD146-induced EMT via repression of the key EMT transcriptional factor Slug. Our study revealed the molecular details of the complex signaling networks during CD146-induced EMT, and provided important clues for future exploration of the mechanisms underlying the association between CD146 and TNBC as observed in the clinic. BIOLOGICAL SIGNIFICANCE: This study used a proteomics screen to reveal molecular changes mediated by CD146-induced epithelial-mesenchymal transition (EMT) in breast cancer cells. Estrogen receptor (ER) was found to be the most significantly inhibited transcription regulator, which mediated its effects on CD146-induced EMT via repression of the transcriptional factor Slug. Elucidation of protein interaction networks and signal networks generated from 103 significantly changed proteins would facilitate future investigation into the mechanisms underlying CD146 induced-EMT in breast cancers.

Targeting endothelial CD146 attenuates colitis and prevents colitis-associated carcinogenesis.

Recently, enhanced CD146 expression was reported on endothelial cells in intestinal biopsies from patients with inflammatory bowel disease. However, the underlying mechanism remains unknown. Here, we found that overexpressed endothelial CD146 promoted the inflammatory responses in inflammatory bowel disease, which further potentiated the occurrence of colitis-associated colorectal carcinogenesis. Eliminating endothelial CD146 by conditional knockout significantly ameliorated the severity of inflammation in two different murine models of colitis, and decreased tumor incidence and tumor progression in a murine model of colitis-associated colorectal carcinogenesis. Mechanistic study showed that cytokine tumor necrosis factor-α (TNF-α) up-regulated the expression of endothelial CD146 through NF-κB transactivation. In turn, the enhanced endothelial CD146 expression promoted both angiogenesis and proinflammatory leukocyte extravasations, contributing to inflammation. Using an anti-CD146 antibody, AA98, alone or together with an anti-TNF-α antibody significantly attenuated colitis and prevented colitis-associated colorectal carcinogenesis in mice. Our study provides the first evidence that CD146 plays a dual role on endothelium, facilitating leukocyte extravasations and angiogenesis, thus promoting inflammation. This finding not only reveals the function and regulating mechanism of CD146 in inflammatory bowel disease, but also provides a promising therapeutic strategy for treating inflammatory bowel disease and preventing colitis-associated colorectal carcinogenesis.

FXYD6: a novel therapeutic target toward hepatocellular carcinoma.

FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.

Effect of short message service on infant feeding practice: findings from a community-based study in Shanghai, China.

IMPORTANCE: Appropriate infant feeding practices have the potential for long-term health effects. However, research findings on improving early infant feeding practices are limited. The wide use of mobile phone short message service (SMS) provides new opportunities for health promotion and services. OBJECTIVE: To assess the effect of an SMS intervention on infant feeding practices. DESIGN AND SETTING: Quasiexperimental design with follow-up measures scheduled at 4, 6, and 12 months at 4 community health centers in Shanghai, China. Two community health centers represented the intervention group, and 2 other community health centers represented the control group. PARTICIPANTS: In total, 582 expectant mothers were recruited during the first trimester. Expectant mothers were eligible to participate if they owned a mobile phone, were first-time mothers, conceived a singleton fetus, were older than 20 years and less than 13 weeks' gestation, had completed at least a compulsory junior high school education, and had no illness that limited breastfeeding after childbirth. INTERVENTION: Mothers in the intervention group received weekly SMS messages about infant feeding from the third trimester to 12 months' post partum. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of exclusive breastfeeding (EBF). Survival analysis was used to compare the duration of EBF between the intervention group and the control group. RESULTS: Compared with the control group, the intervention group had a significantly longer median duration of EBF at 6 months (11.41 [95% CI, 10.25-12.57] vs 8.87 [95% CI, 7.84-9.89] weeks). The hazard ratio for stopping EBF in the intervention group was 0.80 (95% CI, 0.66-0.97). The intervention resulted in a significantly higher rate of EBF at 6 months (adjusted odds ratio, 2.67 [95% CI, 1.45-4.91]) and a significantly lower rate of the introduction of solid foods before 4 months (adjusted odds ratio, 0.27 [95% CI, 0.08-0.94]). CONCLUSIONS AND RELEVANCE: An SMS intervention may be effective in promoting EBF, delaying the introduction of solid foods, increasing awareness of the World Health Organization breastfeeding guidelines, and improving knowledge of appropriate infant feeding practices for new mothers.

Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension.

Dysregulation of Wnt signalling leads to developmental defects and diseases. Non-canonical Wnt signalling via planar cell polarity proteins regulates cell migration and convergent extension; however, the underlying mechanisms are poorly understood. Here we report that Wnt5a uses CD146 as a receptor to regulate cell migration and zebrafish embryonic convergent extension. CD146 binds to Wnt5a with the high affinity required for Wnt5a-induced activation of Dishevelled (Dvl) and c-jun amino-terminal kinase (JNK). The interaction between CD146 and Dvl2 is enhanced on Wnt5a treatment. Mutation of the Dvl2-binding region impairs its ability to activate JNK, promote cell migration and facilitate the formation of cell protrusions. Knockdown of Dvls impairs CD146-induced cell migration. Interestingly, CD146 inhibits canonical Wnt signalling by promoting ß-catenin degradation. Our results suggest a model in which CD146 acts as a functional Wnt5a receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch.