USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA.

RNA N6-methyladenosine (m6A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m6A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3'-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo, YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m6A modification in SCI and might provide a potential therapy for SCI.SIGNIFICANCE STATEMENT Spinal cord injury is a devastating trauma of the CNS involving motor and sensory impairments. However, epigenetic modification in spinal cord injury is still unclear. Here, we propose an m6A regulation effect of astrocytic METTL3 following spinal cord injury, and we further characterize its underlying mechanism, which might provide promising strategies for spinal cord injury treatment.

Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis.

BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear. METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis. RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation. CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis.

Assessing the utility of MRI-based vertebral bone quality (VBQ) for predicting lumbar pedicle screw loosening.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to assess the potential of utilizing the MRI-based vertebral bone quality (VBQ) score as a predictive tool for pedicle screw loosening (PSL) in patients who have undergone pedicle screw fixation and to identify risk factors associated with VBQ scores. METHODS: One hundred and sixteen patients who had undergone pedicle screw fixation between December 2019 and January 2021 and had more than a year of follow-up were divided into two groups of PSL and non-PSL. The radiological and clinical parameters investigated were age, gender, body mass index, the VBQ score, length of fusion and the DXA T-score. RESULTS: Of the 116 patients included in the study, 22 patients developed pedicle screw loosening after surgery (18.97%). VBQ score of PSL group was higher than the non-PSL group (3.61 ± 0.63 vs. 2. 86 ± 0.43, p < 0.001). According to logistic regression, PSL was independently linked with a higher VBQ score (OR = 3.555, 95% confidence interval [1.620-7.802], p < 0.005). The AUC of predicting screw loosening was 0.774 (p < 0.001) for VBQ score, and the best threshold was 3.055 (sensitivity, 81.8%; specificity, 71.3%). High VBQ score was associated with age (r (114) = 0.29, p = 0.002), while it was not negatively correlated with T-scores of each part. CONCLUSION: VBQ score is an independent predictor of pedicle screw loosening, with higher scores indicating a greater risk. Our results showed that older patients and women had higher VBQ scores.

Manipulating the Rectifying Contact between Ultrafine Ru Nanoclusters and N-Doped Carbon Nanofibers for High-Efficiency pH-Universal Electrocatalytic Hydrogen Evolution.

The rational design of ingenious strategies to boost the intrinsic activity and stability of ruthenium (Ru) is of great importance for the substantial progression of water electrolysis technology. Based on Mott-Schottky effect, electronic regulation within a metal/semiconductor hybrid electrocatalyst represents a versatile strategy to boost the electrochemical performance. Herein, a typical Mott-Schottky hydrogen evolution reaction (HER) electrocatalyst composed of uniform ultrafine Ru nanoclusters in situ anchored on N-doped carbon nanofibers (abbreviated as Ru@N-CNFs hereafter) through a feasible and scalable "phenolic resin-bridged" strategy is reported. Both spectroscopy analyses and density functional theory calculations manifest that such rectifying contact can induce the spontaneous electron transfer from Ru to N-doped carbon nanofibers to generate a built-in electric field, thus enormously promoting the charge transfer efficiency and HER intrinsic activity. Moreover, the seamless immobilization of Ru nanoclusters on the substrate can prevent the active sites from unfavorable migration, coarsening, and detachment, rendering the excellent structural stability. Consequently, the well-designed Ru@N-CNFs afford prominent pH-universal HER performances with small overpotentials of 16 and 17 mV at 10 mA cm-2 and low Tafel slopes of 31.8 and 28.5 mV dec-1 in acidic and alkaline electrolytes, respectively, which are superior to the state-of-the-art commercial Pt/C and Ru/C benchmarks.

Sodium butyrate exerts antioxidant stress effects and attenuates Aß25-35-induced cytotoxicity in PC12 cells.

Alzheimer's disease (AD), a common neurodegenerative disease, is characterised by the deposition of amyloid-ß (Aß) plaques and neurofibrillary tangles. An increasing number of studies have demonstrated that Aß causes neuronal damage and mitochondrial dysfunction. Herein, we evaluated the neuroprotective effect of sodium butyrate (NaB) against Aß induced neurotoxicity in PC12 cells. The results revealed that 3 mM of NaB promoted the expression of angiotensin-converting enzyme and brain-derived neurotrophic factor, which exert a neuroprotective effect by activating G protein-coupled receptors. Moreover, NaB could significantly improve mitochondrial dysfunction caused by Aß. In conclusion, NaB protected PC12 cells from Aß-induced cell damage, highlighting the potential of NaB in AD treatment.

Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis.

BACKGROUND: Vanishing white matter (VWM) is an autosomal recessive disorder characterized by childhood ataxia with central hypomyelination. Adult-onset VWM should be considered as a differential diagnosis for suspected cases of multiple sclerosis (MS). METHODS: Targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutations in a family with VWM. RESULTS: The main clinical manifestations of the proband included decreased vision and sleepiness accompanied by atrophy of the corpus callosum, affected inner rim of the corpus callosum, decreased apparent diffusion coefficient value or persistent hyperintensity-diffusion-weighted imaging, atrophied optic nerve, and no recordable visual evoked potentials. Due to the slow development and atypical VWM image features, MS was initially suspected. After prednisone was administered, the patient's condition did not improve significantly, and other diseases were considered. The TRS and Sanger sequencing identified compound heterozygous mutations of EIF2B3 in the proband; c.965C > G /p.Ala322Gly in exon 8 and c.130G > A/p.Glu44Lys in exon 2 were missense mutations inherited from the mother and father, respectively. The proband's oldest brother had the same compound heterozygous mutations but showed no symptoms. CONCLUSION: This is the first report of adult-onset VWM in a Chinese family. Initially, MS was suspected, and genetic testing confirmed the diagnosis of VWM. This study may further broaden the clinical spectrum of EIF2B3, thus providing a foundation for further research on the pathogenesis and genetic therapy for VWM.

Radiographic predictors for recurrence of lumbar symptoms after prioritized cervical surgery in patients with tandem spinal stenosis.

OBJECTIVES: The purpose of the current study was to explore radiographic predictors for recurrence of lumbar symptoms after prioritized cervical surgery in patients with tandem spinal stenosis (TSS). METHODS: The current retrospective cohort study included 74 patients with TSS, who underwent prioritized cervical surgery. Based on presence or absence of improvement in lower limb symptoms, patients were grouped into improved and non-improved groups. Medical records and radiological parameters including age, sex, body mass index, cervical and lumbar parameters were analyzed. In improved group, patients were divided into relapsed and non-relapsed groups based on recurrence in lower limb symptoms. RESULTS: Lumbar symptoms improved in 70.1% (n = 52) of patients. Comparison between the improved and non-improved group showed that there were no statistically significant differences in cervical parameters while comparisons between the relapsed and non-relapsed groups showed significant differences in redundant nerve roots (RNRs) (p = 0.029), narrow segment (p = 0.042) and lumbar stenosis index (LSI) (p = 0.003). In multivariate logistic regression analysis, LSI > 10 (p = 0.016) was independently associated with recurrence of lumbar symptoms. CONCLUSIONS: Finding of the current study indicated that LSI > 10 was associated with recurrence of lumbar symptoms in TSS patients following cervical surgery.

Improvement of AD-Census Algorithm Based on Stereo Vision.

Problems such as low light, similar background colors, and noisy image acquisition often occur when collecting images of lunar surface obstacles. Given these problems, this study focuses on the AD-Census algorithm. In the original Census algorithm, in the bit string calculated with the central pixel point, the bit string will be affected by the noise that the central point is subjected to. The effect of noise results in errors and mismatching. We introduce an improved algorithm to calculate the average window pixel for solving the problem of being susceptible to the central pixel value and improve the accuracy of the algorithm. Experiments have proven that the object contour in the grayscale map of disparity obtained by the improved algorithm is more apparent, and the edge part of the image is significantly improved, which is more in line with the real scene. In addition, because the traditional Census algorithm matches the window size in a fixed rectangle, it is difficult to obtain a suitable window in the image range of different textures, affecting the timeliness of the algorithm. An improvement idea of area growth adaptive window matching is proposed. The improved Census algorithm is applied to the AD-Census algorithm. The results show that the improved AD-Census algorithm has been shown to have an average run time of 5.3% and better matching compared to the traditional AD-Census algorithm for all tested image sets. Finally, the improved algorithm is applied to the simulation environment, and the experimental results show that the obstacles in the image can be effectively detected. The improved algorithm has important practical application value and is important to improve the feasibility and reliability of obstacle detection in lunar exploration projects.

Establishment and validation of prognosis model for patients with cerebral contusion.

BACKGROUND AND OBJECTIVE: Cerebral Contusion (CC) is one of the most serious injury types in patients with traumatic brain injury (TBI). In this study, the baseline data, imaging features and laboratory examinations of patients with CC were summarized and analyzed to develop and validate a prediction model of nomogram to evaluate the clinical outcomes of patients. METHODS: A total of 426 patients with cerebral contusion (CC) admitted to the People's Hospital of Qinghai Province and Affiliated Hospital of Qingdao University from January 2018 to January 2021 were included in this study, We randomly divided the cohort into a training cohort (n = 284) and a validation cohort (n = 142) with a ratio of 2:1.At Least absolute shrinkage and selection operator (Lasso) regression were used for screening high-risk factors affecting patient prognosis and development of the predictive model. The identification ability and clinical application value of the prediction model were analyzed through the analysis of receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Twelve independent prognostic factors, including age, Glasgow Coma Score (GCS), Basal cistern status, Midline shift (MLS), Third ventricle status, intracranial pressure (ICP) and CT grade of cerebral edema,etc., were selected by Lasso regression analysis and included in the nomogram. The model showed good predictive performance, with a C index of (0.87, 95% CI, 0.026-0.952) in the training cohort and (0.93, 95% CI, 0.032-0.965) in the validation cohort. Clinical decision curve analysis (DCA) also showed that the model brought high clinical benefits to patients. CONCLUSION: This study established a high accuracy of nomogram model to predict the prognosis of patients with CC, its low cost, easy to promote, is especially applicable in the acute environment, at the same time, CSF-glucose/lactate ratio(C-G/L), volume of contusion, and mean CT values of edema zone, which were included for the first time in this study, were independent predictors of poor prognosis in patients with CC. However, this model still has some limitations and deficiencies, which require large sample and multi-center prospective studies to verify and improve our results.

Analysis for interaction between interleukin-35 genes polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population.

BACKGROUND: The relationship between IL-35 genes polymorphism and susceptibility to coronary heart disease has not been tested in the largest Han population in China. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) of interleukin-35 (IL-35) genes and its relationship with environment on the risk of coronary heart disease (CHD). METHODS: We performed Hardy-Weinberg equilibrium test on the control group. The relationship between the four SNPs of IL-35 genes and the risk of coronary heart disease was studied by multivariate logistic regression. The best interaction was identified with generalized multifactor dimensionality reduction (GMDR). Logistic regression was used for investigation on association between four SNPs and CHD risk. RESULTS: Logistic regression analysis showed that the C allele of rs428253 and the G allele of rs2243115 were independently correlated with increased risk of CHD, and adjusted ORs (95% CI) were 1.91 (1.28-2.64) and 1.80 (1.30-2.23), respectively. However, there was no significant association between CHD and rs4740 or rs568408. GMDR model indicated a best model for CHD risk consisted of rs428253 and current smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.010). Therefore, this overall multi-dimensional model had the highest cross-validation consistency, regardless of how the data were divided. This provided an evidence of gene-environment interaction effects. We also found that current smokers with rs428253-GC/CC genotype have the highest CHD risk, compared to never smokers with rs428253-GG genotype, OR (95% CI) = 3.04 (1.71-4.41), after adjustment for age, gender, hypertension, T2DM and alcohol consumption status. CONCLUSIONS: In this study, the C allele of rs428253 and the G allele of rs2243115, and the interaction rs428253 and current smoking were correlated with increased risk of CHD.

Antiwetting and Antifouling Performances of Different Lubricant-Infused Slippery Surfaces.

The concept of slippery lubricant-infused surfaces has shown promising potential in antifouling for controlling detrimental biofilm growth. In this study, nontoxic silicone oil was either impregnated into porous surface nanostructures, referred to as liquid-infused surfaces (LIS), or diffused into a polydimethylsiloxane (PDMS) matrix, referred to as a swollen PDMS (S-PDMS), making two kinds of slippery surfaces. The slippery lubricant layers have extremely low contact angle hysteresis, and both slippery surfaces showed superior antiwetting performances with droplets bouncing off or rolling transiently after impacting the surfaces. We further demonstrated that water droplets can remove dust from the slippery surfaces, thus showing a "cleaning effect". Moreover, "coffee-ring" effects were inhibited on these slippery surfaces after droplet evaporation, and deposits could be easily removed. The clinically biofilm-forming species P. aeruginosa (as a model system) was used to further evaluate the antifouling potential of the slippery surfaces. The dried biofilm stains could still be easily removed from the slippery surfaces. Additionally, both slippery surfaces prevented around 90% of bacterial biofilm growth after 6 days compared to the unmodified control PDMS surfaces. This investigation also extended across another clinical pathogen, S. epidermidis, and showed similar results. The antiwetting and antifouling analysis in this study will facilitate the development of more efficient slippery platforms for controlling biofouling.

Association of genetic variants in lncRNA GAS5/miR-21/mTOR axis with risk and prognosis of coronary artery disease among a Chinese population.

BACKGROUND: Allowing for the significance of single nucleotide polymorphisms (SNPs) in reflecting disease risk, this investigation attempted to uncover whether SNPs situated in lncRNA GAS5/miR-21/mTOR axis were associated with risk and prognosis of coronary heart disease (CHD) among a Chinese Han population. METHODS: Altogether 436 patients with CHD were recruited as cases, and meanwhile, 471 healthy volunteers were included into the control group. Besides, SNPs of GAS5/MIR-21/mTOR axis were genotyped utilizing mass spectrometry. Chi-square test was applied to figure out SNPs that were strongly associated with CHD risk and prognosis, and combined effects of SNPs and environmental parameters on CHD risk were evaluated through multifactor dimensionality reduction (MDR) model. RESULTS: Single nucleotide polymorphisms of GAS5 (ie, rs2067079 and rs6790), MIR-21 (ie, rs1292037), and mTOR (rs2295080, rs2536, and rs1034528) were associated with susceptibility to CHD, and also Gensini score change of patients with CHD (P < .05). MDR results further demonstrated that rs2067079 and rs2536 were strongly interactive in elevating CHD risk (P < .05), while smoking, rs6790 and rs2295080 showed powerful reciprocity in predicting Gensini score change of patients with CHD (P < .05). CONCLUSION: Single nucleotide polymorphisms of lncRNA GAS5/miR-21/mTOR axis might interact with smoking to regulate CHD risk, which was conducive to diagnosis and prognostic anticipation of CHD.

Sublytic C5b-9 induces proliferation of glomerular mesangial cells via ERK5/MZF1/RGC-32 axis activated by FBXO28-TRAF6 complex.

Mesangioproliferative glomerulonephritis (MsPGN) is characterized by the proliferation of glomerular mesangial cells (GMCs) and accumulation of extracellular matrix (ECM), followed by glomerulosclerosis and renal failure of patients. Although our previous studies have demonstrated that sublytic C5b-9 complex formed on the GMC membrane could trigger GMC proliferation and ECM expansion of rat Thy-1 nephritis (Thy-1N) as an animal model of MsPGN, their mechanisms are still not fully elucidated. In the present studies, we found that the levels of response gene to complement 32 (RGC-32), myeloid zinc finger 1 (MZF1), phosphorylated extracellular signal-regulated kinase 5 (phosphorylated ERK5, p-ERK5), F-box only protein 28 (FBXO28) and TNF receptor-associated factor 6 (TRAF6) were all markedly up-regulated both in the renal tissues of rats with Thy-1N (in vivo) and in the GMCs upon sublytic C5b-9 stimulation (in vitro). Further in vitro experiments revealed that up-regulated FBXO28 and TRAF6 could form protein complex binding to ERK5 and enhance ERK5 K63-ubiquitination and subsequent phosphorylation. Subsequently, ERK5 activation contributed to MZF1 expression and MZF1-dependent RGC-32 up-regulation, finally resulting in GMC proliferative response. Furthermore, the MZF1-binding element within RGC-32 promoter and the functions of FBXO28 domains were identified. Additionally, knockdown of renal FBXO28, TRAF6, ERK5, MZF1 and RGC-32 genes respectively markedly reduced GMC proliferation and ECM production in Thy-1N rats. Together, these findings indicate that sublytic C5b-9 induces GMC proliferative changes in rat Thy-1N through ERK5/MZF1/RGC-32 axis activated by the FBXO28-TRAF6 complex, which might provide a new insight into MsPGN pathogenesis.

miR-873-5p inhibits the progression of colon cancer via repression of tumor suppressor candidate 3/AKT signaling.

BACKGROUND AND AIM: We previously discovered that tumor suppressor candidate 3 (TUSC3) was overexpressed and predicted worse prognosis in colon cancer patients. However, the mechanisms of upregulation of TUSC3 in colon cancer remained unclear. METHODS: MiR-873-5p was predicted and identified as the regulator of TUSC3 via online programs and luciferase reporter assays. The roles of miR-873-5p in regulating colon cancer cell proliferation, colony formation, and invasion were evaluated in vitro. Animal studies were performed to investigate the effects of miR-873-5p on proliferation and lung metastasis. Moreover, the miR-873-5p/TUSC3 related signaling pathway and the prognostic value of combining miR-873-5p and TUSC3 for colon cancer patients were also explored. RESULTS: Here, we identified miR-873-5p as a novel regulator of TUSC3 in colon cancer. Functionally, ectopic expression or silencing of miR-873-5p, respectively, inhibited or promoted colon cancer cells proliferation, colony formation, and invasion, as well as prevented or enhanced the metastasis of colon cancer cells in vitro and in vivo. Molecularly, miR-873-5p functioned as a tumor suppressor by inhibiting the TUSC3/AKT pathway. Overexpression or silencing of TUSC3 could partially reverse the effects of the overexpression or repression of miR-873-5p on colon cancer progression caused by activation of the AKT pathway. Clinically, low miR-873-5p expression predicted poor survival in colon cancer patients, especially combined with high TUSC3 expression. CONCLUSIONS: We identified miR-873-5p as a tumor suppressor, which acts by directly repressing TUSC3 in colon cancer.

A multifunctional fluorescent aptamer probe for highly sensitive and selective detection of cadmium(II).

We report a highly sensitive and selective strategy for Cd(II) assay using a singly labeled multifunctional probe consisting of a Cd(II)-specific aptamer (CAP), which acted as a recognition element for Cd(II) and a signal reporter. The presence of Cd(II) can induce the conformational switching of the CAP, accompanied by a change in fluorescence intensity. Thereby, a fluorescence strategy for Cd(II) assay was established. The proposed method has a detection limit of 2.15 nM, which is much lower than the detection limits reported in related literature. This strategy involves only an aptamer probe, and the use of such a G4-based quencher avoids the dual labeling of the CAP with fluorophore/quencher units. It is obviously more convenient and economical than the other aptamer-based biosensors for Cd(II) detection. The mechanism by which Cd(II) induces the CAP to change from a random coil sequence to a stem-loop structure was studied in a series of control experiments. This strategy would be helpful in the design of a sensitive analytical platform for various target assays in environmental and biomedical fields. Graphical Abstract The presence of Cd2+ leads to the conformational change of CAP from a random coil sequence to a stem-loop structure, resulting in a quenching in the fluorescence.

Improved transcatheter aortic valve implantation for aortic regurgitation using a snare loop-assisted device: the first preclinical experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an effective percutaneous treatment for high-risk patients with severe symptomatic aortic stenosis. However, TAVI is rendered less effective in patients with noncalcified aortic valve disease because noncalcified aortic valves lack an anchor site for the implanted stent, causing the stent to relocate to an unexpected position. In this study, we developed an improved TAVI with a snare loop-assisted device, and evaluated the feasibility and safety of this strategy in noncalcified aortic valve disease. MATERIALS AND METHODS: The balloon-expandable valve stent made of cobalt-chromium alloy was cut into a cylindrically shaped mesh configuration. The prosthetic valve was made of bovine pericardium. Ten healthy sheep (six males and four females with an average weight of 27·8 ± 1·18 kg) were selected to undergo transcatheter implantation of valved stents using the snare loop-assisted device. Aortic angiography and colour Doppler echocardiography were applied to assess the function of artificial valves immediately and 3 months after the operation. RESULTS: The snare loop-assisted TAVI was successfully implanted in all 10 sheep. The aortogram showed that the valve stent was fixed in the expected position. Among these 10 sheep, nine sheep survived for more than 3 months normally and one sheep died of infective endocarditis 1 week after the operation. Ultrasound and aortogram in the 3 months after operation showed proper positions of the prosthetic valves without stenosis and other apparent complications, and normal coronary artery openings. CONCLUSIONS: The snare loop-assisted TAVI approach can reduce stent shifting during valve stent implantation and improve the success rate of the TAVI in those with noncalcified aortic valves.

Enhanced efficacy of DNA vaccination against botulinum neurotoxin serotype A by co-administration of plasmids encoding DC-stimulating Flt3L and MIP-3α cytokines.

Targeting antigens encoded by DNA vaccines to the key antigen-presenting cells by chemotactic or growth factors, is an effective strategy for enhancing the potency of DNA vaccinations. Here, we report the effects of chemotactic or growth factors on a DNA vaccine against botulinum neurotoxin serotype A (BoNT/A) in a mouse model. We demonstrated that mice immunized with DNA constructs encoding the Hc domain of BoNT/A (AHc) fused with DC-stimulating Flt3L or MIP-3α cytokines failed to elicit an enhanced or efficacious AHc-specific humoral or protective response in mice. However, the potency of DNA vaccination was significantly modulated and enhanced by co-administration of AHc-expressing DNA with pFlt3L or pMIP-3α, which generated strong immune and protective responses against BoNT/A. Moreover, the enhanced potency was further boosted by co-administration of AHc-expressing DNA with the combination of pFlt3L and pMIP-3α in mice, but not with the Flt3L-MIP-3α fusion molecule, which indicated that co-immunization with both pFlt3L and pMIP-3α could synergistically enhance AHc-specific immune and protective responses against BoNT/A. In summary, our findings indicate that co-administration of plasmids encoding antigen and cytokine rather than administration of plasmids encoding cytokine-antigen fusion is effective to enhance the potency of AHc-expressing DNA vaccine.

4-Year Trajectory of Visceral Adiposity Index in the Development of Type 2 Diabetes: A Prospective Cohort Study.

BACKGROUND/AIMS: Our aim was to evaluate whether visceral adiposity index (VAI) could predict the risk of type 2 diabetes (T2D) in different genders and to compare the predictive ability between VAI and other fatness indices. METHODS: Four thousand seventy-eight participants including 1,817 men and 2,261 women, aged 18 and older and free of T2D at baseline were enrolled in 2010 and followed up for 4 years. New cases of T2D were identified via the annual medical examination. Cox regression analysis was used to assess the association between VAI and incidence of T2D. Receiver operating characteristic curve and area under the curves (AUC) were applied to compare the prediction ability of T2D between VAI and other fatness indices. RESULTS: During the 4-year follow-up, 153 (8.42%) of 1,817 men and 88 (3.89%) of 2,261 women developed T2D. The multivariable-adjusted hazards ratios for developing T2D in the highest tertile of VAI scores were 2.854 (95% CI 1.815-4.487) in men and 3.551 (95% CI 1.586-7.955) in women. The AUC of VAI was not higher than that of other fatness indices. CONCLUSIONS: VAI could predict the risk of T2D among Chinese adults, especially in women. However, the prediction ability of T2D risk for VAI was not higher than that of the other fatness indices.

Dietary patterns and changes in cardiovascular risk factors in apparently healthy Chinese women: a longitudinal study.

Little is known of the relationships between dietary patterns and cardiovascular risk factors in China. We therefore designed a 3-year longitudinal study to evaluate the impacts of dietary patterns on changes in these factors among Chinese women. A total of 1,028 subjects who received health examination in 2011 and 2014 were recruited. Three major dietary patterns ("vegetable pattern", "meat pattern", and "animal offal-dessert-and-alcohol pattern") were derived by principal component analysis based on validated food frequency questionnaires. Cardiovascular risk factors were standardized to create within-cohort z-scores and the changes in them were calculated as the differences between 2011 and 2014. Relationships between dietary patterns and changes in cardiovascular risk factors were assessed using general linear model. After adjustment for potential confounders, changes in total cholesterol and fasting blood glucose decreased across the tertiles of vegetable pattern (p for trend = 0.01 and 0.04, respectively). While, changes in diastolic blood pressure, total cholesterol and low density lipoprotein cholesterol increased across the tertiles of animal offal-dessert-and-alcohol pattern (p for trend = 0.02, 0.01, and 0.02, respectively). The findings suggest that vegetable pattern was beneficially related to cardiovascular risk factors, whereas animal offal-dessert-and-alcohol pattern was detrimental related to these factors among apparently healthy Chinese women.