Laser-Ignited Lipid Peroxidation Nanoamplifiers for Strengthening Tumor Photodynamic Therapy Through Aggravating Ferroptotic Propagation and Sustainable High Immunogenicity.

Photodynamic therapy (PDT) is extensively investigated for tumor therapy in the clinic. However, the efficacy of PDT is severely limited by the tissue penetrability of light, short effective half-life and radius of reactive oxygen species (ROS), and the weak immunostimulatory effect. In this study, a glutathione (GSH)-activatable nano-photosensitizer is developed to load with arachidonic acid (AA) and camouflage by erythrocyte membrane, which serves as a laser-ignited lipid peroxidation nanoamplifier (MAR). The photosensitive effect of MAR is recovered accompanied by the degradation in the tumor microenvironment and triggers the peroxidation of AA upon laser excitation. Interestingly, it aggravates the propagation of ferroptosis among cancer cells by driving the continuous lipid peroxidation chain reactions with the participation of the degradation products, ferrous ions (Fe2+), and AA. Consequently, even the deep-seated tumor cells without illumination also undergo ferroptosis owing to the propagation of ferroptotic signal. Moreover, the residual tumor cells undergoing ferroptosis still maintain high immunogenicity after PDT, thus continuously triggering sufficient tumor-associated antigens (TAAs) release to remarkably promote the anti-tumor immune response. Therefore, this study will provide a novel "all-in-one" nano-photosensitizer that not only amplifies the damaging effect and expands the effective range of PDT but also improves the immunostimulatory effect after PDT.

A method based on improved ant colony algorithm feature selection combined with GWO-SVR model for predicting chlorophyll-a concentration in Wuliangsu Lake.

Chlorophyll-a (Chl-a) is an important parameter in water bodies. Due to the complexity of optics in water bodies, it is difficult to accurately predict Chl-a concentrations in water bodies by current traditional methods. In this paper, using Sentinel-2 remote sensing images as the data source combined with measured data, taking Wuliangsu Lake as the study area, a new intelligent algorithm is proposed for prediction of Chl-a concentration, which uses the adaptive ant colony exhaustive optimization algorithm (A-ACEO) for feature selection and the gray wolf optimization algorithm (GWO) to optimize support vector regression (SVR) to achieve Chl-a concentration prediction. The ant colony optimization algorithm is improved to select remote sensing feature bands for Chl-a concentration by introducing relevant optimization strategies. The GWO-SVR model is built by optimizing SVR using GWO with the selected feature bands as input and comparing it with the traditional SVR model. The results show that the usage of feature bands selected by the presented A-ACEO algorithm as inputs can effectively reduce complexity and improve the prediction performance of the model, under the condition of the same model, which can provide valuable references for monitoring the Chl-a concentration in Wuliangsu Lake.

The preprogrammed anti-inflammatory phenotypes of CD11chigh macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma.

BACKGROUND: Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined. METHODS: BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages. RESULTS: We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg. CONCLUSION: Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.

Sugar intake and risk of hypertension: a systematic review and dose-response meta-analysis of cohort and cross-sectional studies.

Several epidemiological studies have investigated the association between sugar intake, the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the risk of hypertension, but findings have been inconsistent. We carried out a systematic review and meta-analysis of observational studies to examine the associations between sugar intake, hypertension risk, and BP levels. Articles published up to February 2, 2021 were sourced through PubMed, EMBASE and Web of Science. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a fixed- or random-effects model. Restricted cubic splines were used to evaluate dose-response associations. Overall, 35 studies were included in the present meta-analysis (23 for hypertension and 12 for BP). Sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) were positively associated with hypertension risk: 1.26 (95% CI, 1.15-1.37) and 1.10 (1.07-1.13) per 250-g/day increment, respectively. For SBP, only SSBs were significant with a pooled ß value of 0.24 mmHg (95% CI, 0.12-0.36) per 250 g increase. Fructose, sucrose, and added sugar, however, were shown to be associated with elevated DBP with 0.83 mmHg (0.07-1.59), 1.10 mmHg (0.12-2.08), and 5.15 mmHg (0.09-10.21), respectively. Current evidence supports the harmful effects of sugar intake for hypertension and BP level, especially SSBs, ASBs, and total sugar intake.

In vitro and in vivo development of interspecies Asian elephant embryos reconstructed with pig enucleated oocytes.

Interspecies somatic cell nuclear transfer (iSCNT) has an immense potential to rescue endangered animals and extinct species like mammoths. In this study, we successfully established an Asian elephant's fibroblast cell lines from ear tissues, performed iSCNT with porcine oocytes and evaluated the in vitro and in vivo development of reconstructed embryos. A total of 7780 elephant-pig iSCNT embryos were successfully reconstructed and showed in vitro development with cleavage rate, 4-cell, 8-cell and blastocyst rate of 73.01, 30.48, 5.64, and 4.73%, respectively. The total number of elephant-pig blastocyte cells and diameter of hatched blastocyte was 38.67 and 252.75 µm, respectively. Next, we designed species-specific markers targeting EDNRB, AGRP and TYR genes to verify the genome of reconstructed embryos with donor nucleus/species. The results indicated that 53.2, 60.8, and 60.8% of reconstructed embryos (n = 235) contained elephant genome at 1-cell, 2-cell and 4-cell stages, respectively. However, the percentages decreased to 32.3 and 32.7% at 8-cell and blastocyst stages, respectively. Furthermore, we also evaluated the in vivo development of elephant-pig iSCNT cloned embryos and transferred 2260 reconstructed embryos into two surrogate gilts that successfully became pregnant and a total of 11 (1 and 10) fetuses were surgically recovered after 17 and 19 days of gestation, respectively. The crown-rump length and width of elephant-pig cloned fetuses were smaller than the control group. Unfortunately, none of these fetuses contained elephant genomes, which suggested that elephant embryos failed to develop in vivo. In conclusion, we successfully obtained elephant-pig reconstructed embryos for the first time and these embryos are able to develop to blastocyst, but the in vivo developmental failure needs further investigated.

Prediction of lake chlorophyll concentration using the BP neural network and Sentinel-2 images based on time features.

One of the most important indicators of lake eutrophication is chlorophyll-a (Chl-a) concentration, which is also an essential component of lake water quality monitoring. It is an efficient, economical and convenient method to monitor the Chl-a concentration through remote sensing images. Taking the Wuliangsuhai Lake as an example, the relevant bands of Sentinel-2 images were used as the input and the Chl-a concentration as the output to build neural network models. In the process of building the model, we mainly studied and tested the impact of adding time features to the model input on the model accuracy. Through the experiment, it was found that the month and day difference features of remote sensing images and Chl-a measurement could significantly improve the prediction accuracy of Chl-a concentration in varying degrees. Finally, it was determined that the neural network prediction model with 12 bands of Sentinel-2 images combined month features as inputs and one hidden layer, eight neurons and Chl-a concentration as outputs was the best. Then, the accuracy of the model was validated when the test set accounts for 20 and 30%, and good results were obtained.

Delayed body development with reduced triglycerides levels in leptin transgenic pigs.

Leptin is a well-known adipokine that plays critical role in adiposity. To further investigate the role of leptin in adiposity, we utilized leptin overexpressing transgenic pigs and evaluated the effect of leptin on growth and development, fat deposition, and lipid metabolism at tissue and cell level. Leptin transgenic pigs were produced and divided into two groups: elevated leptin expression (leptin ( +)) and normal leptin expression group (control). Results indicated that leptin ( +) pigs had elevated leptin protein and mRNA expression levels and exhibited sluggish growth and development followed by decreased subcutaneous fat thickness, low serum triglycerides, saturated, unsaturated fatty acids and high cholesterol esters (p < 0.05). There were differences in the lipid metabolism related genes at different fat depots, including upregulation of PPARγ, AGPAT6, PLIN2, HSL and ATGL in subcutaneous, PPARγ in perirenal, and FAT/CD36 and PLIN2 in mesenteric adipose tissues and downregulation of AGPAT6 and ATGL in perirenal and AGPAT6 in mesenteric adipose tissues (p < 0.05). Additionally, in-vitro cultured leptin ( +) preadipocytes exhibited upregulation of PPARγ, FAT/CD36, ACACA, AGPAT, PLIN2, ATGL and HSL as compared to control (p < 0.05). These findings suggested that homeostasis imbalance in lipolysis and lipogenesis at adipose tissue and adipocytes levels led to low subcutaneous fat depots in leptin overexpression pigs. These pigs can act as model for obesity and related metabolic disorder.

Fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus, and hypertension in adults: a meta-analysis of observational studies.

Recent studies have reported conflicting associations of fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus (T2DM) and hypertension, and a meta-analysis is not available. We aimed to explore the association between fried-food consumption and risk of overweight/obesity, T2DM and hypertension in adults through a meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published up to 17 June 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. In comparing the highest to lowest fried-food intake, the pooled RRs (95% CIs) were 1.16 (1.07-1.25; I2 = 71.0%, Pheterogeneity < 0.001) for overweight/obesity (cohort: 1.19 [0.97-1.47], n = 2; cross-sectional: 1.14 [1.03-1.27], n = 9), 1.07 (0.90-1.27; 84.7%) for T2DM (cohort: 1.01 [0.89-1.15], n = 9; case-control: 2.33 [1.80-3.01], n = 1), and 1.20 (1.05-1.38; I2=91.8%) for hypertension (cohort: 1.06 [0.98-1.15], n = 8; cross-sectional: 2.16 [0.59-7.87], n = 3). Our meta-analysis indicates fried-food consumption is associated with increased risk of overweight/obesity and hypertension but not T2DM in adults, but the findings should be interpreted with caution due to high heterogeneity and unstable subgroup analyses of this meta-analysis. More studies are warranted to investigate the total fried-food consumption and these health outcomes.

Angelica Sinensis Polysaccharide Suppresses the Aging of Hematopoietic Stem Cells Through Sirt1/FoxO1 Signaling.

BACKGROUND: This study investigated the anti-aging effects of Angelica sinensis polysaccharide (ASP) on mouse hematopoietic stem cells (HSCs) and related mechanisms. METHODS: Seventy-two C57BL/6J mice were randomly divided into the following three groups (n = 24 per group): control group; aging group, in which mice were irradiated with X-ray uniformly to establish the aging model of HSCs; and ASP group, in which mice were given 200 mg/kg ASP during irradiation. HSCs were collected by immunomagnetic beads, transmission electron microscopy was used to examine the morphological changes in HSCs, SA-ß-Gal staining was used to detect the aging cells, immunofluorescence staining was used to detect the reactive oxygen species (ROS), and western blotting was used to evaluate the expression levels of sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1). RESULTS: HSCs in the control group had an intact cytoplasmic structure and many mitochondria. In the aging group, HSCs had many vacuoles in the cytoplasm, and few and irregular mitochondria. In the ASP group, HSCs had a normal cytoplasmic structure and more mitochondria compared with the aging group. The aging group had a significantly higher positive rate of HSCs SA-ß-Gal staining and ROS production than the control group (p < 0.05), but had lower expression of Sirt1 and FoxO1 (p < 0.05). These patho(physio)logical changes were ameliorated by ASP treatment (all p < 0.05). CONCLUSIONS: ASP inhibits irradiation-induced oxidative stress and aging of HSCs at least in part by regulating the Sirt1/FoxO1 pathway, thereby delaying aging of HSCs in mice.

Exosomes Derived from Mouse Adipose-Derived Mesenchymal Stem Cells Alleviate Benzalkonium Chloride-Induced Mouse Dry Eye Model via Inhibiting NLRP3 Inflammasome.

PURPOSE: The objective of the study was to investigate efficacy and mechanisms of mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in the benzalkonium chloride (BAC)-induced mouse dry eye model. METHODS: Exosomes in the mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, and transmission electron microscopy were used to characterize mADSC-Exos. An experimental mouse model of dry eye was established by instillation of 0.2% BAC. mADSC-Exos were administered following BAC treatment. The positive control group was treated with commercial eye drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, and tear film break-up time (BUT) were evaluated, and histologic analysis of the cornea and conjunctiva was performed by hematoxylin and eosin and periodic acid-Schiff staining. Apoptosis in the corneal epithelium was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and by Western blotting. Levels of pro-inflammatory cytokines in the cornea and conjunctiva were evaluated by flow cytometry, and mRNA and protein levels of NLR family pyrin domain-containing 3 (NLRP3) pathway components were assessed by quantitative real-time PCR and Western blotting, respectively. RESULTS: mADSC-Exos were characterized as vesicles with a bilayer membrane. The particle size distribution peak was at 134 nm. mADSC-Exos specifically expressed cluster of differentiation (CD)9, CD63, and CD81. mADSC-Exos treatment repaired ocular surface damage. Additionally, mADSC-Exos inhibited cell apoptosis, decreased the levels of interleukin (IL)-1ß, IL-6, IL-1α, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, and increased levels of the anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation and upregulation of caspase-1, IL-1ß, and IL-18 were reversed by mADSC-Exos. CONCLUSIONS: mADSC-Exos alleviate ocular surface inflammation, suggesting that it is a promising treatment for dry eye.

In Vitro Anti-Inflammatory Activity of Three Peptides Derived from the Byproduct of Rice Processing.

Inflammation is a contributing factor to the initiation and progression of many diseases, and some food-derived biofunctional peptides show high anti-inflammatory activity. In our previous study, we demonstrated that peptides derived from trypsin hydrolysis of rice protein show good immunological activity. In the present study, proteins of broken rice were extracted and identified by macroporous resin fractionation and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Subsequently, a bioinformatics prediction and in silico simulation approach was used to screen for peptides showing anti-inflammatory activity, including inhibition of the production of nitric oxide and proinflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) by lipopolysaccharide-stimulated RAW264.7 mice macrophages. Three peptides (DNIQGITKPAIR, IAFKTNPNSMVSHIAGK, and IGVAMDYSASSKR) that demonstrated the highest binding affinity were synthesized, and their in vitro anti-inflammatory activity was investigated. This is the first study that integrates LC-MS/MS identification and bioinformatics prediction for reporting the anti-inflammatory activity of anti-inflammatory peptides derived from broken rice protein. The study findings revealed that the peptides derived from the byproduct of rice milling could be potentially used as natural anti-inflammatory alternativities.

Long non-coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis.

Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.

LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. METHODS: The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. RESULTS: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. CONCLUSIONS: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

Chinese visceral adiposity index: A reliable indicator of visceral fat function associated with risk of type 2 diabetes.

BACKGROUND: The evidence of the association between Chinese visceral adiposity index (CVAI) and risk of type 2 diabetes mellitus (T2DM) is limited. We explored the association of CVAI with T2DM and directly compared with the predictive power of CVAI with other visceral obesity indices (visceral adiposity index, waist to height ratio, waist circumference and body mass index) based on a large prospective study. METHODS: We conducted a population-based study of 12 237 Chinese participants. Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CVAI and T2DM. RESULTS: During follow-up (median: 6.01 years), the incidence of T2DM was 3.29, 7.34, 12.37 and 23.72 per 1000 person-years for quartiles 1, 2, 3 and 4 of CVAI, respectively. The risk of T2DM was increased with quartiles 2, 3 and 4 vs quartile 1 of CVAI (HR 2.12 [95% CI 1.50-3.00], 2.94 [2.10-4.13] and 5.01 [3.57-7.04], Ptrend < 0.001). Per-SD increase in CVAI was associated with a 72% increased risk of T2DM (HR 1.72 [95% CI 1.56-1.88]). Sensitivity analyses did not alter the association. The area under receiver operating characteristic curve was significantly higher for CVAI than other visceral obesity indices (all P <.001). Similar results were observed in stratified analyses by sex. CONCLUSIONS: Our findings show a positive association between CVAI and risk of T2DM. CVAI has the best performance in predicting incident T2DM, so the index might be a reliable and applicable indicator identifying people at high risk of T2DM.

Genetic polymorphisms in the PCNXL2 gene are risk factors for thyroid cancer in the Chinese population.

Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45 years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45 years, while this SNP decreased thyroid cancer risk at age ≤45 years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45 years. An association was observed between rs6424270 and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938 and rs4649295 was the best model to predict thyroid cancer. Conclusion: This study suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.

Dose-response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies.

BACKGROUND: We conducted a systematic review and meta-analysis from published cohort studies to examine the association of adult height and all-cause mortality and to further explore the dose-response association. METHODS: PubMed, The Cochrane Library, The Ovid, CNKI, CQVIP and Wanfang databases were searched for articles published from database inception to 6 February 2018. We used the DerSimonian-Laird random-effects model to estimate the quantitative association between adult height and all-cause mortality and the restricted cubic splines to model the dose-response association. RESULTS: We included 15 articles, with 1 533 438 death events and 2 854 543 study participants. For each 5-cm height increase below the average, the risk of all-cause mortality was reduced by 7% [relative risk (RR) = 0.93, 95% confidence interval (CI), 0.89-0.97] for men and 5% (RR = 0.95, 95% CI, 0.90-0.99) for women. All-cause mortality had a U-shaped association with adult height, the lowest risk occurring at 174 cm for men and 158 cm for women (both Pnonlinearity < 0.001). Relative to the shortest adult height (147 cm for men and 137 cm for women), men at 174 cm had a 47% lower likelihood of all-cause mortality and women at 158 cm a 33% lower risk of all-cause mortality. CONCLUSIONS: Our study suggests that the relation between adult height and all-cause mortality is approximately U-shaped in both men and women.

Effects of 2,4-dichlorophenoxyacetic acid on the expression of NLRP3 inflammasome and autophagy-related proteins as well as the protective effect of Lycium barbarum polysaccharide in neonatal rats.

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) has neurotoxic effects, but its mechanism is not clear. In this study, a 2,4-D (75 mg/kg. b.w) exposure model was established in SD rats with colostrum. Lipopolysaccharide (1 mg/kg b.w) was used as the positive control, and Lycium barbarum polysaccharide (LBP, 50 mg/kg b.w) was used as an intervention factor to explore the neurotoxic effect of 2,4-D and the neuroprotective effect of LBP. Our research results show that 2,4-D causes a decrease in the number of hippocampal CA3 pyramidal cells and pyknosis in nuclei with a triangular or irregular shape and that rats show signs of anxiety or depression. In rat serum, superoxide dismutase, and glutathione peroxidase activity decreased, while malondialdehyde content increased. Protein and mRNA levels of TNFα, IL-6, IL-1ß, IL-18, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and p62 increased, while those of LC3-II/LC3-I and Beclin-1 decreased in hippocampal tissues. In conclusion, 2,4-D increased the oxidative stress level, induced neuroinflammatory response, and decreased the autophagy level in experimental rats. LBP may have upregulated the autophagy level in the body by inhibiting the activation of the NLRP3 inflammasome, thus playing a neuroprotective role.

IL-1B rs2853550 polymorphism contributes to esophageal cancer susceptibility in Chinese Han population of Northwest China.

BACKGROUND: Esophageal cancer (EC) is one of the most common human cancers, with a particularly aggressive behavior and increased incidence worldwide. The aim of this study was to assess the associations of single-nucleotide polymorphisms (SNPs) in IL-1B with the risk of EC in a northwest Chinese Han population. METHODS: In order to evaluate the correlations between IL-1B polymorphisms and EC risk, an Agena MassARRAY platform was used to determine the genotype of the candidate SNPs among 384 EC patients and 499 controls. The associations between IL-1B variants and EC risk were examined using logistic regression analysis with adjustment for gender and age. Haplotype construction and analysis were performed to detect the potential associations between haplotypes within IL-1B and EC susceptibility. Additionally, bioinformatics databases were used for gene expression analysis and SNP functional prediction. RESULTS: A significant relationship was found between IL-1B rs2853550 and an increased risk of EC in the allele model [odds ratio (OR) = 1.38, 95% confidence interval (95% CI): 1.01-1.89, p = 0.041), the codominant model (A/G, OR = 1.63, 95% CI: 1.10-2.42, p = 0.011), and the dominant model (OR = 1.49, 95% CI: 1.02-2.18, p = 0.041). Functional analysis revealed the potential effects of rs2853550, which further reinforced its influence on EC susceptibility. However, there were no statistically significant differences for other SNPs or haplotypes between EC cases and healthy controls. Expression analysis conducted with dataset indicated that the expression level of IL-1B was higher in EC cases than that in normal samples. CONCLUSIONS: This study demonstrated that rs2853550 in IL-1B might increase EC susceptibility in the Chinese Han population of Northwest China.

IL-1RN gene polymorphisms reduces thyroid cancer risk in Chinese Han population.

The purpose of this study was to investigate the effect of IL-1RN polymorphisms on thyroid cancer (TC) risk in Han population. Genotypes of four single nucleotide polymorphisms (SNPs) (rs17042888, rs928940, rs3181052, and rs452204) were analyzed by Agena MassARRAY. Meanwhile, we used the logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), and significant differences were evaluated by t test and χ2 test. Findings found that allele "G" of rs452204 and rs3181052 in interleukin-1 receptor antagonist (IL-1RN) reduced the risk of TC. (OR = 0.72, 95% CI = 0.55-0.94, p = .017; OR = 0.73, 95% CI = 0.56-0.94, p = .017, respectively). Hierarchical analysis indicated that three SNPs (rs17042888, rs3181052, and rs452204) significantly reduced the risk of TC among females or individuals older than 48 years (p < .05). Our findings indicate that IL-1RN polymorphisms may contribute to a protective role against TC risk.

Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype-phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype-phenotype relationships for ASD by using phenotype-restricted cohorts.