ICAM-1-related noncoding RNA accelerates atherosclerosis by amplifying NF-κB signaling.

Long noncoding RNAs (lncRNAs) are critical regulators of inflammation with great potential as new therapeutic targets. However, the role of lncRNAs in early atherosclerosis remains poorly characterized. This study aimed to identify the key lncRNA players in activated endothelial cells (ECs). The lncRNAs in response to pro-inflammatory factors in ECs were screened through RNA sequencing. ICAM-1-related non-coding RNA (ICR) was identified as the most potential candidate for early atherosclerosis. ICR is essential for intercellular adhesion molecule-1 (ICAM1) expression, EC adhesion and migration. In a high fat diet-induced atherosclerosis model in mice, ICR is upregulated in the development of atherosclerosis. After intravenous injection of adenovirus carrying shRNA for mouse ICR, the atherosclerotic plaque area was markedly reduced with the declined expression of ICR and ICAM1. Mechanistically, ICR stabilized the mRNA of ICAM1 in quiescent ECs; while under inflammatory stress, ICR upregulated ICAM1 in a nuclear factor kappa B (NF-κB) dependent manner. RNA-seq analysis showed pro-inflammatory targets of NF-κB were regulated by ICR. Furthermore, the chromatin immunoprecipitation assays showed that p65 binds to ICR promoter and facilitates its transcription. Interestingly, ICR, in turn, promotes p65 accumulation and activity, forming a positive feedback loop to amplify NF-κB signaling. Preventing the degradation of p65 using proteasome inhibitors rescued the expression of NF-κB targets suppressed by ICR. Taken together, ICR acts as an accelerator to amplify NF-κB signaling in activated ECs and suppressing ICR is a promising early intervention for atherosclerosis through ICR/p65 loop blockade.

Association between FADS1 rs174547 and levels of long-chain PUFA: a meta-analysis.

In the present study, we analysed the effects of SNP rs174547 (T/C) in the fatty acid desaturase 1 (FADS1) gene on long-chain PUFA levels. Four databases were searched to retrieve related literature with keywords such as fatty acid (FA), SNP, FADS1 and rs174547. A meta-analysis of the data was performed using Stata12.0 software, including summary statistics, test for heterogeneity, evaluation of publication bias, subgroup analysis and sensitivity analysis. The associations between rs174547 in FADS1 and seven types of FA, and Δ-5 (D5D) and Δ-6 fatty acid desaturase (D6D) activity were assessed based on the pooled results from eleven papers. A total of 3713 individuals (1529 TT and 2184 TC + CC) were included. The results demonstrated that minor C allele carriers of rs174547 had higher linoleic acid (LA; P < 0·001) and α-linolenic acid (P = 0·020) levels, lower γ-linolenic acid (GLA; P = 0·001) and arachidonic acid (P = 0·024) levels, and lower D5D (P = 0·005) and D6D (P = 0·004) activities than the TT genotype group. Stratification analysis showed that minor C allele carriers of rs174547 had higher LA and lower GLA levels and lower D6D activities in plasma (LA, P < 0·001; GLA, P < 0·001; D6D activity, P < 0·001) samples and in Asian populations (LA, P < 0·001; GLA, P = 0·001; D6D activity, P = 0·001) than the TT genotype group. In conclusion, minor C allele carriers of the SNP rs174547 were associated with decreased activity of D5D and D6D.

Effect of DHA supplements during pregnancy on the concentration of PUFA in breast milk of Chinese lactating mothers.

OBJECTIVE: To determine whether there is an effect of prenatal supplementation with docosahexaenoic acid (DHA) on the concentration of polyunsaturated fatty acids (PUFAs) in the breast milk of Chinese lactating women. METHODS: A total of 409 participants were recruited at the postpartum care center during their 1-month postpartum care. They were assigned to the supplement group or the control group according to whether or not DHA supplements were taken during pregnancy. Dietary intake was assessed with a food frequency questionnaire (FFQ). Breast milk samples were collected on 1 day between the 22nd and 25th day postpartum and levels of eight kinds of fatty acids in the breast milk were measured by gas chromatography. RESULTS: DHA intake was divided into three levels (<57 mg/day, 57-185 mg/day and >185 mg/day). The concentration of DHA postpartum in the breast milk of the group receiving a DHA supplement >185 mg/day was significantly higher (P=0.003) compared to the control group. CONCLUSIONS: DHA intake >185 mg/day resulted in increased DHA concentrations in breast milk. This finding suggests that mothers with inadequate dietary intake of DHA should change their dietary habits to consume a diet rich in DHA or take sufficient DHA supplements to meet the average nutritional needs of infants.

Computational prediction and experimental validation identify functionally conserved lncRNAs from zebrafish to human.

Functional studies of long noncoding RNAs (lncRNAs) have been hindered by the lack of methods to assess their evolution. Here we present lncRNA Homology Explorer (lncHOME), a computational pipeline that identifies a unique class of long noncoding RNAs (lncRNAs) with conserved genomic locations and patterns of RNA-binding protein (RBP) binding sites (coPARSE-lncRNAs). Remarkably, several hundred human coPARSE-lncRNAs can be evolutionarily traced to zebrafish. Using CRISPR-Cas12a knockout and rescue assays, we found that knocking out many human coPARSE-lncRNAs led to cell proliferation defects, which were subsequently rescued by predicted zebrafish homologs. Knocking down coPARSE-lncRNAs in zebrafish embryos caused severe developmental delays that were rescued by human homologs. Furthermore, we verified that human, mouse and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs with their conserved functions relying on specific RBP-binding sites. Overall, our study demonstrates a comprehensive approach for studying the functional conservation of lncRNAs and implicates numerous lncRNAs in regulating vertebrate physiology.

Expression and functional characterization of odorant-binding protein 2 in the predatory mite Neoseiulus barkeri.

Olfaction plays a crucial role for arthropods in foraging, mating, and oviposition. The odorant-binding protein (OBP) gene is considered one of the most important olfactory genes. However, little is known about its functions in predatory mites. Here, we used Neoseiulus barkeri, an important commercialized natural pest control, to explore the chemosensory characteristics of OBP. In this study, N. barkeri was attracted by methyl salicylate (MeSA) and showed higher crawling speeds under MeSA treatment. Then, we identified and cloned an OBP gene named Nbarobp2 and analyzed its expression profiles in the predatory mite. Nbarobp2 was 663 bp, was highly expressed in larval and nymphal stages, and was significantly upregulated in N. barkeri under MeSA treatment. Nbarobp2 encoded 202 amino acid residues with a molecular weight of 23 kDa (after removing the signal peptide). Sequence comparisons revealed that the OBPs in Arachnida shared 6 conserved cysteine sites, but were distinguishable from the OBPs of Insecta on the phylogenetic tree. RNA interference, Western blotting, and binding affinity assays further proved that Nbarobp2 was involved in volatile perception in predatory mites. This study shed light on the functional characteristics of OBPs in predatory mites, providing a new insight for better biological control.

Counterintuitive relationship between the triglyceride glucose index and diabetic foot in diabetes patients: A cross-sectional study.

BACKGROUND: Research has shown that insulin resistance (IR) is a known risk factor for diabetic foot (DF), and the triglyceride-glucose (TyG) index is a reliable and simple indicator of IR. However, less is known about the relationship between the TyG and the risk of DF. Here, we investigated the association between the TyG index and the prevalence of DF. METHODS: The eligible records from the Departments of Endocrinology of Shandong Provincial Hospital Affiliated to Shandong First Medical University were screened (from December 1, 2012, to December 31, 2021), and a total of 8866 patients were enrolled. The TyG index was calculated as ln[(fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2)]. The continuous variables between the DF and the non-DF groups were compared by Student's t test or the Mann-Whitney U test, and categorical variables were compared by the chi-square test. Receiver operating characteristic curve (ROC) analysis was carried out to estimate the predictive value of the TyG index for DF. Logistic regression models were used to evaluate the associations between the quartiles of the TyG index and the risk of DF. Subgroup and sensitivity analyses were conducted. RESULTS: The TyG index was significantly lower in the DF group than in the no-DF group. The logistic regression revealed that an increased TyG index was associated with a lower risk of DF after adjusting for potential confounders. In addition, an ROC analysis indicated the discriminatory ability of the TyG index in DF presence with an area under the curve (AUC) of 0.661 (95% CI 0.642-0.680, P < 0.001). Subgroup and sensitivity analysis also supported these robust results. CONCLUSIONS: The TyG index was inversely and dose-dependently associated with the risk of DF in diabetes patients, indicating that elevated TyG index was a protective factor for DF. Future studies are therefore warranted to confirm our finding and to explore the detailed pathological mechanism involved in this process.

Highly reproducible and cost-effective one-pot organoid differentiation using a novel platform based on PF-127 triggered spheroid assembly.

Organoid technology offers sophisticatedin vitrohuman models for basic research and drug development. However, low batch-to-batch reproducibility and high cost due to laborious procedures and materials prevent organoid culture standardization for automation and high-throughput applications. Here, using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly through a mechanism different from plate coating, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron, hepatic, and lung organoids with improved reproducibility compared to previous methods while reducing the original costs by 80%-95%. In addition, we adapt our platform to microfluidic chips allowing automated culture. We showcase that our platform can be applied to tissue-specific screening, such as drug toxicity and transfection reagents testing. Finally, we generateNEAT1knockout tissue-specific organoids and showNEAT1modulates multiple signaling pathways fine-tuning the differentiation of nephron and hepatic organoids and suppresses immune responses in cortical organoids. In summary, our strategy provides a powerful platform for advancing organoid research and studying human development and diseases.

Body composition of the upper limb associated with hypertension, hypercholesterolemia, and diabetes.

The associations between segmental body composition and metabolic diseases remain equivocal. This study aimed to investigate this association using the example of U.S. adults. This cross-sectional study included 12,148 participants from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariable logistic regression models were used to estimate associations between segmental body composition quartiles of hypertension, hypercholesterolemia, and diabetes. Among 12,148 participants, 3,569, 5,683, and 1,212 had hypertension, hypercholesterolemia, and diabetes, respectively. After adjusting for potential confounders, increased percent upper limb lean body mass was associated with a lower risk of hypertension (OR= 0.88, 95%CI: 0.84, 0.92, P trend<0.001), hypercholesterolemia (OR= 0.93, 95%CI: 0.89, 0.96, P trend<0.001), and diabetes (OR= 0.96, 95%CI: 0.95, 0.98, P trend<0.001). Increased upper limb fat mass is associated with an increased risk of hypertension (OR= 1.11, 95%CI: 1.07, 1.15, P trend<0.001), hypercholesterolemia (OR= 1.05, 95%CI: 1.01, 1.09, P trend=0.07), and diabetes (OR= 1.03, 95%CI: 1.01, 1.05, P trend=0.014). The same correlations were found in the torso and whole-body composition parameters. We observed that for women, lean body mass has a better protective effect on metabolic diseases [hypertension (OR= 0.88, 95%CI: 0.82, 0.93), hypercholesteremia (OR =0.86, 95%CI: 0.81, 0.92), diabetes (OR= 0.97, 95%CI: 0.85, 0.99)]; for men, increased body fat is associated with greater risk of metabolic disease[hypertension (OR= 1.24, 95%CI: 1.15, 1.33), hypercholesteremia (OR =1.09, 95%CI: 1.01, 1.18), diabetes (OR= 1.06, 95%CI: 1.01, 1.10)]. There were significant differences between different gender. These findings suggested that upper limb and torso adiposity should be considered when assessing chronic metabolic disease risk using body composition.

Sustaining induced heat shock protein 70 confers biological thermotolerance in a high-temperature adapted predatory mite Neoseiulus barkeri (Hughes).

BACKGROUND: In fluctuating climatic environments, heat acclimation in predatory mites is a superior adaptation strategy for effective agricultural pest management and can be used to enhance the abilities critical in biological control efficiency. We investigated the regulatory mechanism governing the remarkable plastic response of thermotolerance in a high-temperature adapted strain (HTAS) and discerned the differences in the defensive reactions between the HTAS and the conventional strain (CS) in the predatory mite Neoseiulus barkeri. RESULTS: At 42 °C, the relative expression levels of four identified HSP70 genes increased rapidly in both N. barkeri strains; meanwhile the expression of NbHSP70-1 and NbHSP70-2 in CS sharply decreased after 4 h, displaying a distinct contrast with the remaining elevated expression in HTAS. Western blot analysis showed that the protein level of NbHSP70-1 in CS was dramatically elevated at 0.5 h and decreased at 6 h at 42 °C. Conversely, in HTAS, NbHSP70-1 was constantly induced and peaked at 6 h at 42 °C. Furthermore, HSP70 suppression by RNAi knockdown had a greater influence on the survival of HTAS, causing a higher mortality under high temperature than CS. Finally, the recombinant exogenous NbHSP70-1 protein enhanced the viability of E. coli BL21 under a lethal temperature of 50 °C. CONCLUSION: Sustained accumulation of HSP70 proteins results in predatory phytoseiid mites with the thermotolerance advantage that could promote their biological control function to pests. The divergent constitutive regulation of HSP70 to a thermal environment is conducive to the flexible adaptability of predators in the higher trophic level to trade off under extremely adversity stress.

Evaluation of glycemic index, antioxidant capacity, and metabolic effects of a fermented beverage made from Changbai Mountain fruit and vegetables.

Fermented foods and beverages have been known to be beneficial when included in the human diet. This study examined the glycemic index (GI) of a fermented beverage (FB) made from Changbai Mountain fruit and vegetables in humans and its antioxidant capacity and metabolic effects in a rat model of diabetes. Twenty healthy volunteers were tested with 50 g of glucose and 50 g equivalent of carbohydrates from FB on two separate days for GI measurement. The rats were randomly divided into blank control group (n = 15) and diabetic model (DM) group (n = 75). DM group were randomly divided into five groups, positive control group, model control group and three FB treatment (2.5, 5, 10 ml/kg·bw·d) groups. The general indices, including blood glucose and lipid levels and antioxidant index, of the rats were measured to investigate the effect of FB. The GI of FB was found to be 56.99, indicating it as a medium GI food. Compared to model control group, the low-dose FB group had lower blood glucose levels and higher high-density lipoprotein cholesterol levels in DM rats (p < .05). Medium- and high-dose FB decreased the serum malonaldehyde levels in DM rats compared to those in the model control group. The FB-treated DM rat groups showed increased serum glutathione and superoxide dismutase levels compared with those in the model control group (p < .05). FB is a medium GI food that plays a protective role against oxidative stress in DM rats. PRACTICAL APPLICATIONS: The present study evaluated the glycemic index of a fermented beverage (FB) made from Changbai Mountain fruit and vegetables in humans and investigated its antioxidant capacity and metabolic effects in a rat diabetes model. The study results may aid in the development of FB from fruits and vegetables and provide a theoretical basis for further research and development.

Acidic pH transiently prevents the silencing of self-renewal and dampens microRNA function in embryonic stem cells.

Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here, we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells (mESCs). Importantly, acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions. Furthermore, acidic pH partially blocks the differentiation of human ESCs (hESCs). Mechanistically, acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs. Interestingly, AGO1 protein is also downregulated by acidic pH in cancer cells. Altogether, this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells (PSCs).

CO2 drives the pine wood nematode off its insect vector.

Insects have developed special organs, spiracles and the trachea, for oxygen-carbon dioxide exchange to adapt to terrestrial life. The plant-parasitic nematode Bursaphelenchus xylophilus, also known as pine wood nematode (PWN), is vectored by pine sawyer beetles (Monochamus spp.) and causes destructive pine wilt disease, threatening the safety and stability of pine forest ecosystems. Unlike the free-living nematode model species Caenorhabditis elegans, PWN have two distinct life stages (dispersive and propagative), each requiring a unique host relationship ranging from symbiotic/commensal to parasitic. Its symbiotic vector beetle and the pine tree it ultimately infects represent dramatically different host environments within which it needs to successfully maneuver. In Asia, the symbiotic relationship between PWN and its host vector M. alternatus is very close (Figure S1A, see Supplemental Information). Previous studies have shown that third-stage juveniles (JIII) are attracted by specific terpenes produced by mature insect larvae and aggregate around pupal chambers in diseased trees [1] and fourth-stage juveniles (JIV) are attracted to newly eclosed adults by ascarosides the beetles secrete [2]. These JIV, sometimes up to 200,000 per beetle [3], then enter the tracheal system of the newly eclosed beetle, which is full of CO2, for dispersal. Later, those nematodes depart from the spiracles to invade new healthy trees via the feeding wounds on pine branches made during beetles' feeding, thus starting a new cycle of infection, propagation and dispersal. The mechanism mediating the nematodes' departure remains unknown and remains an important unsolved focal point in the PWN life cycle. Our experimental evidence suggests acute CO2 avoidance triggers this behavior.

Effects of the rs3834458 Single Nucleotide Polymorphism in FADS2 on Levels of n-3 Long-chain Polyunsaturated Fatty Acids: A Meta-analysis.

OBJECTIVES: Evaluate the effects of the single nucleotide polymorphism (SNP) rs3834458 in the fatty acid desaturase 2 gene (FADS2) on n-3 long-chain polyunsaturated fatty acid (LC-PUFA) levels using statistical meta-analysis. METHODS: Literatures pertaining to the relationship between the SNP rs3834458 and LC-PUFA were retrieved from three electronic databases. Original information was analyzed using RevMan 5.3, including single statistics, test for heterogeneity, summary statistics and evaluation of publication bias. RESULTS: In total, five pieces of literature were retrieved and divided into seven trials. We observed that the minor allele (Tdel+deldel) carriers of rs3834458 had higher linolenic acid levels (P < 0.00001) and lower eicosapentaenoic acid (P < 0.00001), docosapentenoic acid (P = 0.005) and docosahexaenoic acid (P < 0.00001) levels compared to those of carrying major allele homozygote (TT). CONCLUSION: This meta-analysis indicates that minor allele of rs3834458 in FADS2 may result in lower activity of delta-6 desaturase leading to higher ALA and lower EPA, DPA and DHA in blood.

Acute cerebral infarction following a Trimeresurus stejnegeri snakebite: A case report.

RATIONALE: Acute cerebral infarction after snake bites is rare. The underlying mechanism causing the thrombotic process remains complex and unknown. PATIENT CONCERNS: We herein describe a 49-year-old female who was bitten by a Trimeresurus stejnegeri. After 4 days of biting, she developed acute ischemic infarct. DIAGNOSIS: The patient exhibited right side weakness and speech disturbances. Brain computed tomography (CT) scan showed no sign about cerebral hemorrhage symptoms, and brain magnetic resonance imaging (MRI) showed acute ischemic infarct in the left territory. The patient confirmed a diagnosis of acute cerebral infarction following a T. stejnegeri bite. INTERVENTIONS: The patient received an injection of polyvalent anti-snake venom serum, neuroprotective therapy, and anti-platelet aggregate treatment. OUTCOMES: At the 3-month follow-up visit, the patient's left lower extremity swelling disappeared, the right limb muscle strength recovered, and the modified Rankin scale (mRS) score was 4 points. LESSONS: The patient was diagnosed with acute ischemic infarct interrelated to snake bite; further investigations were needed to ascertain mechanism. The clinicians should pay more attention to identify potential victims of neurologic complications, to reduce the mortality rate of snake bite.

Dietary patterns affect maternal macronutrient intake levels and the fatty acid profile of breast milk in lactating Chinese mothers.

OBJECTIVES: Fatty acids (FA) in human milk play an important role in meeting the nutritional demands and promoting the growth and development of breastfeeding infants. Breast milk FA is sensitive to maternal dietary habits, and dietary patterns are better used to explain the effect of diet on FA. Few studies have examined the association between maternal dietary patterns and the FA components of breast milk in developing countries. In this study, we aimed to determine whether dietary patterns affect the FA profile of breast milk in lactating Chinese mothers with the overall goal to optimize the management of infant feeding. METHODS: A total of 274 lactating women ranging from 22 d to 6 mo postpartum were included, and samples of their breast milk were collected together with completed questionnaires. Using a principal component analysis, four dietary patterns were identified in a rotated component matrix. FA profiles were detected using capillary gas chromatography and presented as the percentage by weight of total FA. RESULTS: Maternal intake of energy, carbohydrates, and proteins showed differences between the different dietary patterns. In addition, there were significant differences in the total proportions of saturated, polyunsaturated, and ω-6 polyunsaturated fatty acids in breast milk among the four patterns (P < 0.001; P = 0.025; P = 0.038, respectively). CONCLUSIONS: The results demonstrate that maternal dietary patterns can affect macronutrient intake levels and milk FA profiles in lactating Chinese women. These results are of great significance in understanding how a maternal diet can both improve maternal macronutrient intake and the FA nutritional status of breast milk.

Association of the FADS gene cluster with coronary artery disease and plasma lipid concentrations in the northern Chinese Han population.

We investigated the association of single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster with coronary artery disease (CAD) in a case-control study and evaluated the possible influence of genetic variation on total cholesterol (TC) and triglyceride concentrations in the controls. In total, 497 CAD patients and 495 unrelated controls were genotyped for eight SNPs in the FADS gene cluster, and the blood lipid levels of subjects were measured. Three genetic models, including codominant, dominant and recessive, were used to analyze the genotypic relationship with CAD and plasma lipid levels. Single locus genotypic analysis revealed that rs1000778 in FADS3 under a recessive model (AA vs. GG-GA) was significantly associated with CAD adjusted for risk factors. The rs1000778 minor allele AA was associated with a lower risk of CAD (OR =0.37, 95% CI: 0.15-0.89, P=0.025). In the control group, there were significant differences in TC concentrations under a recessive genetic model for rs174575 (C/G) in FADS2 and for rs174450 (A/C) and rs7115739 (G/T) in FADS3 (P=0.053, 0.016 and 0.018, respectively). The rs1000778-G variant in FADS3 may contribute to the susceptibility of CAD, but the result needs to be further confirmed because of small sample size in our study. Genetic variations in FADS2 and FADS3 influence TC concentration in the northern Chinese Han population.

Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers.

BACKGROUND: The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. DESIGN: Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. RESULTS: A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. CONCLUSION: Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women.