Search

Abstract Background The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN). Methods In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN. Results The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90–14.25), 6.92 (2.51–19.08), and 7.33 (2.69–20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09–4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%. Conclusions The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Abstract Background Hematopoietic stem cell transplantation (HSCT) was associated with potentially life-threatening complications. Among patients supported by extracorporeal membrane oxygenation (ECMO), those who underwent HSCT had a worse prognosis than those who did not. Advances in HSCT and critical care management have improved the prognosis of ECMO-supported HSCT patients. Case The patient in the remission stage of lymphoma after 22 months of allogeneic hematopoietic stem cell transplantation, suffered from ARDS, severe neutropenia, thrombocytopenia, and long-term COVID-19. We evaluated the benefits and risks of ECMO for the patient, including the possibility of being free from ECMO, the status of malignancy, the interval from HSCT to ARDS, the function of the graft, the amount of organ failure, and the comorbidities. ECMO was ultimately used to save his life. Conclusions We did not advocate for the general use of ECMO in HSCT patients and we believed that highly selected patients, with well-controlled tumors, few comorbidities, and fewer risk factors for death, tended to benefit from ECMO with well ICU management.

BackgroundAluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity.ObjectiveTo explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)3].MethodsBV2 cells were assigned to five groups: one control group, three Al(mal)3 exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L−1 Al(mal)3 respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L−1 C188-9 +160 μmol·L−1 Al(mal)3]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA.ResultsThe results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)3 dose. Compared with the control group, the cell viability of the Al(mal)3 high-dose group was decreased by 18% (P0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)3 high-dose group (P0.05).ConclusionAluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

ABSTRACTChilling injury is the dominant factor for quality deterioration and marketability suffers of cucumber fruit during low-temperature storage. Nitric oxide (NO) is a kind of endogenous signaling molecule that significantly regulates the abiotic stress response. In the current investigation, the membrane lipid and energy metabolism were investigated after cucumber fruit was exposed to a sodium nitropruside (SNP) solution that acts as a NO donor before being kept at 4°C for 12 days. The results illustrated that SNP treatment reduced chilling injury and lightened the increase in membrane permeability under cold stress, maintaining a better quality. Subsequently, SNP regulated lipid metabolism by reducing the expression of genes encoding PLA, PLD, lipase, and LOX and decreasing the activities. Compared to the control, the SNP-treated fruit exhibited higher ATP and EC (energy charge) levels. Moreover, SNP-treated suppressed the decrease of H+-ATPase, Ca2+-ATPase, SDH, and CCO activity, which is involved in energy metabolism. The above results showed that exogenous nitric oxide might be an effective method to alleviate the chilling damage in postharvest cucumber fruit by modifying membrane lipids and energy metabolism.

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug–ocular–epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

BackgroundAluminum and fluoride are neurotoxic, and aluminum exposure alone is closely related to the overall cognitive function of operational workers. It is unclear about the effect of aluminum and fluoride interactions on cognitive function.ObjectiveTo evaluate a potential interaction effect of blood aluminum and urinary fluoride on the overall cognitive function of workers working in an aluminum plant.MethodsUsing cluster sampling, 230 workers in the electrolysis workshop of an aluminum group company in Shanxi Province were selected, and plasma aluminum concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) and urinary fluoride by ion-selective electrode. The study participants were divided into a low blood aluminum group and a high blood aluminum group according to the median (M) of blood aluminum concentration, and a low urinary fluoride group and a high urinary fluoride group by a predetermined cutoff point (2.160 mg·L−1). The Montreal Cognitive Assessment-Beijing (MoCA-BJ) was used to assess overall cognitive function of the workers. Logistic regression model was used to analyze the relationship between blood aluminum, urinary fluoride, and mild cognitive impairment (MCI), including multiplicative interaction analysis and correlation analysis; R language was used to fit an additive interaction model of blood aluminum and urinary fluoride on MCI and to calculate synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (API).ResultsAmong the 230 operational workers, the median blood aluminum concentration (P25, P75) was 40.11 (25.16, 58.89) µg·L−1, and there were 104 cases of abnormal urinary fluoride, with an abnormality rate of 45.2%. There was a multiplicative interaction (OR=7.783, 95%CI: 1.377, 43.991) and no additive interaction (RERI=0.030, 95%CI: −0.498, 0.559; API=0.018, 95%CI: −0.279, 0.316; S=1.049, 95%CI: 0.519, 2.118) for the effect between blood aluminum and urinary fluoride on overall cognitive function of the workers. The logistic regression analysis showed that the risk of MCI was 12.105 (95%CI: 2.802, 52.287) times higher in workers with both high blood aluminum and high urinary fluoride than in those with low blood aluminum and low urinary fluoride, after adjusting for selected influencing factors.ConclusionOccupational exposure related high blood aluminum and high urinary fluoride are risk factors for cognitive dysfunction, and the coexistence of both indicators increases the risk of MCI in workers with occupational aluminum exposure, with a multiplicative interaction.

BackgroundPrevious studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet.ObjectiveTo evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers.MethodsA total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models.ResultsThe workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P0, Ptrend0.05).ConclusionOccupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Abstract Background Panax quinquefolius saponin (PQS) is the main active component of Panax quinquefolius. Emerging evidence suggests that PQS exerts beneficial effects against cardiovascular diseases. However, the role and mechanism of PQS in vascular calcification are not unclear. The present study investigated the effects of PQS on the calcification of vascular smooth muscle cell (VSMCs). Methods The present study used calcification medium containing 3 mM inorganic phosphate (Pi) to induce rat VSMCs calcification. We investigated the effects of PQS on VSMCs calcification using alizarin red staining and alkaline phosphatase (ALP) activity assays. The intracellular reactive oxygen species (ROS) levels and the transcriptional activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined. The mRNA and protein expression levels of Nrf2, the antioxidant gene heme oxygenase-1 (HO-1), osteogenic markers, including runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and Kelch-like ECH-associated protein 1 (Keap1) were also measured. Results Treatment with Pi significantly increased intracellular calcium deposition and ALP activity, which were suppressed by PQS in a concentration-dependent manner. During VSMCs calcification, PQS inhibited the mRNA and protein expression of Runx2 and BMP2. PQS treatment reduced intracellular ROS production and significantly upregulated Nrf2 transcriptional activity and the expression of Nrf2 and its target antioxidant gene HO-1. PQS suppressed the Pi-induced protein expression of Keap1, which is an endogenous inhibitor of Nrf2. Keap1 siRNA treatment induced Nrf2 expression and downregulated Runx2 expression in the presence of Pi and PQS. Conclusion Taken together, these findings suggest that PQS could effectively inhibit VSMCs calcification by ameliorating oxidative stress and regulating osteogenic genes via the promotion of Nrf2 expression.

BackgroundOccupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. ObjectiveTo explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. MethodsThis study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score

In order to characterize the quality characteristics of three varieties of mango (Tainong, Xiangya and Jinhuang), the main quality indexes of mango was determined and a comprehensive scoring model of main quality of mango was established by principal component analysis (PCA). The volatile flavor compounds of mango were analyzed by HS-SPME-GC-MS technology, and its quality and processing characteristics were evaluated comprehensively. The results showed that the content of soluble solids, total sugar and sugar acid ratio of Jinhuang were the highest, which were 19%, 24.18 mg/g and 10.86 respectively; The contents of VC and total phenol in Tainong were the highest, which were 9.52 mg/100 g and 1.03 mg/g respectively; The results of PCA analysis showed that the comprehensive score of Tainong was the highest, indicating that its comprehensive quality was the best, followed by Jinhuang, and the comprehensive score of Xiangya was the lowest. A total of 116 volatile compounds were detected from three mangoes by HS-SPME-GC-MS, mainly including olefins, phenols and aldehydes. The volatile compounds of Tainong and Xiangya were mainly olefins, with relative contents of 45.52% and 58.12% respectively. The volatile compounds of Jinhuang were mainly phenols, with relative contents of 56.88%. Fifteen key flavor compounds were identified from three mango varieties by the analysis of relative activity value (ROAV). Among them, (E,Z)-2,6-nonadienal contributed the most to the aroma in Tainong and Xiangya, 3-hexenal contributed the most to the aroma in Jinhuang; Tainong had citrus and sweet aroma, Xiangya had cucumber flavor, and Jinhuang had special wood flavor, which was mainly contributed by 2,4-di-tert-butylphenol. Comprehensive analysis showed that Tainong and Xiangya were suitable for deep processing, while Jinhuang was more suitable for fresh food.

Vinyl-capped cationic waterborne polyurethane (CWPU) was prepared using isophorone diisocyanate (IPDI), polycarbonate diol (PCDL), N-methyldiethanolamine (MDEA), and trimethylolpropane (TMP) as raw materials and hydroxyethyl methacrylate (HEMA) as a capping agent. Then, a crosslinked FPUA composite emulsion with polyurethane (PU) as the shell and fluorinated acrylate (PA) as the core was prepared by core-shell emulsion polymerization with CWPU as the seed emulsion, together with dodecafluoroheptyl methacrylate (DFMA), diacetone acrylamide (DAAM), and methyl methacrylate (MMA). The effects of the core-shell ratio of PA/PU on the surface properties, mechanical properties, and heat resistance of FPUA emulsions and films were investigated. The results showed that when w(PA) = 30~50%, the stability of FPUA emulsion was the highest, and the particles showed a core-shell structure with bright and dark intersections under TEM. When w(PA) = 30%, the tensile strength reached 23.35 ± 0.08 MPa. When w(PA) = 50%, the fluorine content on the surface of the coating film was 14.75% and the contact angle was as high as 98.5°, which showed good hydrophobicity; the surface flatness of the film was observed under AFM. It is found that the tensile strength of the film increases and then decreases with the increase in the core-shell ratio and the heat resistance of the FPUA film is gradually increased. The FPUA film has excellent properties such as good impact resistance, high flexibility, high adhesion, and corrosion resistance.

BackgroundOccupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction.ObjectiveTo explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers.MethodsA total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP).ResultsThe M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%.ConclusionOccupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

Introduction Painless gastrointestinal endoscopy is being increasingly practised in the clinical field. The management and choice of sedation are important during the endoscopy procedure to reduce patient discomfort and facilitate high disease detection rates. Ciprofol is principally an agonist of the γ-aminobutyric acid type A receptor; it comprises the active ingredient HSK3486, which is similar to the currently used intravenous anaesthetic propofol in clinical practice. A systematic review and meta-analysis comparing ciprofol and propofol will be conducted to assess their efficacy and safety during endoscopy. Before starting the study, we describe the specific protocol of this systematic review.Methods and analysis This protocol was prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be searched: Embase, Cochrane Library, PubMed, Web of Science, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and a clinical trial registry. The database search strategy will adopt a combination of subject words and free words. Randomised controlled trials related to ciprofol use for sedation during gastrointestinal endoscopy will also be included. Based on the inclusion and exclusion criteria, two researchers will independently screen the articles and extracted data. Following the qualitative evaluation of each study, analysis will be conducted using Review Manager software.Ethics and dissemination The protocol for this systematic review and meta-analysis involves no individual patient data; thus, ethical approval is not required. This will be the first meta-analysis to assess the sedation efficacy of ciprofol and provide evidence to clinicians for decision-making. The results will be disseminated through conference presentations and publications in peer-review journals related to this field.PROSPERO registration number CRD42022370047.

Aim: Existing targeted therapies for hepatocellular carcinoma (HCC) are resistant and have limitations. It is crucial to find new HCC-related target genes.Methods: RNA-sequencing data of HCC were gathered from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Initially, differentially expressed genes between normal and tumor tissues were identified from four Gene Expression Omnibus datasets, GSE36376, GSE102079, GSE54236, and GSE45267. GO terms and KEGG pathway enrichment analyses were performed to explore the potential biological functions of differentially expressed genes. A PPI network was constructed by using the STRING database, and up-regulated and down-regulated hub genes were defined through 12 topological approaches. Subsequently, the correlation bounded by up-regulated genes and down-regulated genes in the diagnosis, prognosis, and clinicopathological features of HCC was analyzed. Beyond a shadow of doubt, the key oncogene PBK and tumor suppressor gene F9 were screened out, and the specific mechanism was investigated through GSEA enrichment analysis and immune correlation analysis. The role of PBK in HCC was further verified by western blot, CCK8, transwell, and tube formation experiments.Results:CDCA5, CDC20, PBK, PRC1, TOP2A, and NCAPG are good indicators of HCC diagnosis and prognosis. The low expressions of F9, AFM, and C8B indicate malignant progression and poor prognosis of HCC. PBK was found to be closely related to VEGF, VEGFR, and PDGFR pathways. Experiments showed that PBK promotes HCC cell proliferation, migration, invasion, and tube formation in HUVEC cells. F9 was negatively correlated with the degree of immune infiltration, and low expression of F9 suggested a poor response to immunotherapy.Conclusion: The role of HCC-related oncogenes and tumor-suppressor genes in diagnosis and prognosis was identified. In addition, we have found that PBK may promote tumor proliferation through angiogenesis and F9 may be a predictor of tumor immunotherapy response.

Coal workers’ pneumoconiosis (CWP) is a fatal occupational disease caused by inhalation of coal dust particles, which leads to progressive pulmonary fibrosis. Recently, as new signal carriers for intercellular communication, exosomal miRNAs have been validated in the pathogenesis of multiple diseases. However, the research on exosomal miRNAs in CWP is still in the preliminary stage. Here, using miRNA sequencing, exosomal miRNA profiles in bronchoalveolar lavage fluid (BALF) from rats with pulmonary fibrosis induced by coal dust particles were analyzed, and the underlying biological function of putative target genes was explored by GO term analysis and KEGG pathway enrichment analysis. According to the results, intratracheal instillation of coal dust particles can alter the exosomal miRNAs expression in the BALF of rats. Further bioinformatics analysis provided some clues to reveal their function in pathological process of pneumoconiosis. More importantly, we identified 4 differentially expressed exosomal miRNAs (miRNA-21–5p, miRNA-29a-3p, miRNA-26a-5p, and miRNA-34a-5p) by qRT‑PCR and further verified the temporal changes in the expression of these exosomal miRNAs in animal models from 2 weeks to 16 weeks postexposure. In addition, we conducted a preliminary study on Smad7 as a potential target of miRNA-21–5p and found that exosomal miRNA 21–5p/Smad7 may contribute to the pulmonary fibrosis induced by coal dust particles. Our study confirmed the contribution of exosomal miRNAs to coal dust particle-induced pulmonary fibrosis and provided new insights into the pathogenesis of CWP.

Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD.

Background Idiopathic granulomatous mastitis (IGM) can clinically and radiographically mimic an abscess or breast cancer. Although IGM is benign, it can cause the breast skin to appear “riddled with holes” and can even result in the loss of the breast. The optimal treatment has not been established. Methods We retrospectively studied the medical records of 200 patients with IGM who were treated for skin rupture from June 2015 to June 2017 in our institute. The patients’ treatment modalities (including surgery after steroid therapy and steroid therapy alone), outcomes, and scores of satisfaction questionnaires were analyzed. The time to healing and recurrence rate were compared with a focus on the treatment modalities to identify the most effective treatments for IGM. Results The median follow-up time was 15.64 months (range, 12–36 months). In total, 156 patients were treated with surgery after steroid therapy and 44 were treated with steroid therapy alone. The median times to healing in the surgical and nonsurgical groups were 25 and 258 days, respectively (p = 0.003). Four of 156 (2.56%) patients developed post-excision wound complications. Eight of 156 patients (5.1%) in the surgical group and 10 of 44 (22.7%) patients in the nonsurgical group developed recurrence (p

OBJECTIVES:. The aim was to evaluate the effect of dihydropyridine calcium channel blocker on the prognosis for moderate-severe pulmonary acute respiratory distress syndrome in hypertension patients. DESIGN:. A retrospective, observational, multicenter cohort study. SETTING:. A total of 307 patients without propensity score matching and 186 adult inpatients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome in five teaching hospitals in Jiangsu province, China, from December 2015 to December 2020 were enrolled. PATIENTS:. A total of 307 patients without propensity score matching and 186 patients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome were included in the final analysis. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Demographic characteristics and clinical characteristics were recorded. The propensity score matching method was used to eliminate the difference between group with dihydropyridine calcium channel blocker and group without dihydropyridine calcium channel blocker. The primary outcome was in-hospital mortality. We used univariate and multivariate regression analyses for both patients with or without propensity score matching to assess the effect of these variables on mortality. In the subset of 186 patients with propensity score matching, in-hospital mortality was 53.2%. Inpatient mortality was significantly higher in patients treated with dihydropyridine calcium channel blocker than in those not treated with dihydropyridine calcium channel blocker of patients without propensity score matching (65.4% vs 40.4%; p < 0.01). Multivariate analysis for patients without propensity score matching showed that dihydropyridine calcium channel blocker (hazard ratio, 1.954; 95% CI, 1.415–2.699), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 3.809; 95% CI, 2.106–4.531), and lactate greater than or equal to 2 mmol/L (hazard ratio, 1.454; 95% CI, 1.041–2.029) were independently associated with in-hospital mortality. Based on univariate analysis for patients with propensity score matching, dihydropyridine calcium channel blocker (hazard ratio, 2.021; 95% CI, 1.333–3.064), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 4.379; 95% CI, 2.642–7.257), and lactate greater than or equal to 2 mmol/L (hazard ratio, 2.461; 95% CI, 1.534–3.951) were independently associated with in-hospital mortality. In contrast, patients not treated with dihydropyridine calcium channel blocker had a significant survival advantage over those treated with dihydropyridine calcium channel blocker in both patients without or with propensity score matching (p < 0.001; p = 0.001 by Kaplan-Meier analysis). CONCLUSIONS:. Dihydropyridine calcium channel blocker, lactate dehydrogenase greater than or equal to 600 U/L, and lactate greater than or equal to 2 mmol/L at admission were independent risk factors for patients with hypertension and moderate-severe pulmonary acute respiratory distress syndrome.

Previous studies have explored associations between betaine and diabetes, but few have considered the effects of genes on them. We aimed to examine associations between serum betaine, methyl-metabolizing genetic polymorphisms and the risk of type 2 diabetes in Chinese adults. This prospective study comprised 1565 subjects aged 40–75 without type 2 diabetes at baseline. Serum betaine was measured by high-performance liquid chromatography tandem mass spectrometry. Genotyping of methyl-metabolizing genes was detected by Illumina ASA-750K arrays. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 8.9 years of follow-up, 213 participants developed type 2 diabetes. Compared with participants in the lowest quartile of serum betaine, those in the highest quartile had lower risk of type 2 diabetes, adjusted HRs (95%CIs) was 0.46 (0.31, 0.69). For methylenetetrahydrofolate reductase (MTHFR) G1793A (rs2274976) and MTHFR A1298C (rs1801131), participants carrying 1793GA + AA and 1298AC + CC had lower risk of type 2 diabetes. Interactions of serum betaine and genotype of MTHFR G1793A and MTHFR A1298C could be found influencing type 2 diabetes risk. Our findings indicate that higher serum betaine, mutations of MTHFR G1793A and A1298C, as well as the joint effects of them, are associated with lower risk of type 2 diabetes.

BackgroundCoronavirus disease 2019 (COVID-19) has spread to the world. Whether there is an association between lifestyle behaviors and the acquisition of COVID-19 remains unclear.MethodsIn this case-control study, we recruited 105 patients with SARS-CoV-2 infection as a case group from the Wuhan Tongji Hospital (Wuhan, China). For each case two control subjects were recruited. Participants were randomly selected from communities in Wuhan and matched for sex, age (± 2yrs), and pre-existing comorbidities (hypertension and diabetes).ResultsA total of 105 patients diagnosed with COVID-19 and 210 controls were included. Compared with control group, the case group had higher proportions of lack of sleep (30.5% vs. 14.8%, P = 0.001) and increased physical activities (56.2% vs. 32.9%, P < 0.001). And patients in the case group were more likely to have alopecia (28.6% vs. 10.0%, P < 0.001) than people from the control group. Overall, we found that lack of sleep [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 1.03-2.39)], physical activities (≥ 5 times a week) (adjusted OR 2.05, 95%CI 1.39-3.02) and alopecia (adjusted OR 1.73, 95%CI 1.13-2.66) were independent risk factors for COVID-19 infection. Conversely, low-dose alcohol intake (ConclusionsIndividual lifestyle behaviors and health status can affect the occurrence of COVID-19.

Loop-mediated isothermal amplification (LAMP) technology has been applied in a wide range of fields such as detection of foodborne bacteria and clinical pathogens due to its simplicity and efficiency. However, existing LAMP primer designing systems require a conserved gene or a short genome region as input, and they can’t design group-specific primers. With the growing number of whole genomes available, it is possible to design better primers to target a set of genomes with high specificity based on whole genomes. We present here a whole Genome based LAMP primer designer (GLAPD), a new system to design LAMP primer for a set of target genomes using whole genomes. Candidate single primer regions are identified genome wide and then combined into LAMP primer sets. For a given set of target genomes, only primer sets amplifying them and only these genomes will be output. In order to accelerate the primer designing, a GPU version is provided as well. The effectiveness of primers designed by GLAPD has been assessed for a wide range of foodborne bacteria. GLAPD can be accessed at http://cgm.sjtu.edu.cn/GLAPD/ or https://github.com/jiqingxiaoxi/GLAPD.git. A simple online version is also supplied to help users to learn and test GLAPD: http://cgm.sjtu.edu.cn/GLAPD/online/.

Identification of microbe-disease associations provides insight into the mechanism that microbes cause diseases at the molecular level. Existing microbe-disease association prediction methods mainly utilize microbe-disease association profiles to calculate microbe-microbe similarities and disease-disease similarities, and then build similarity-based prediction models. However, they ignore important biological knowledge, e.g., disease Medical Subject Headings (MeSH), and do not consider unequal contributions of microbe information and disease information. In this paper, we propose the bi-direction similarity integration label propagation (BDSILP) method for predicting microbe-disease associations. First, BDSILP introduces disease MeSH to calculate the disease-disease semantic similarity and the microbe-microbe functional similarity. Although MeSH is not available for all diseases, BDSILP presents a strategy for integrating multiple similarities for microbes and diseases. Second, two graphs are constructed by using integrated disease similarity and integrated microbe similarity, and BDSILP implements the label propagation on the graphs to score microbe-disease pairs. Third, BDSILP adopts the weighted averages of their scores as final predictions. BDSILP produces better performances than existing state-of-the-art methods, achieving the AUC of 0.9131 and the AUPR of 0.5343 in leave-one-out cross validation, and achieving the AUC of 0.9051 and the AUPR of 0.3037 in five-fold cross validation. Moreover, case studies and discussion demonstrate that BDSILP is promising for predicting novel microbe-disease associations.

Abstract This study aimed to explore the link between various forms of obesity, including body mass index (BMI) and waist circumference (WC), and the risk of dyslipidemia among Chinese residents. We selected the study population through a multi-stage random sampling method from permanent residents aged 35 and older in Ganzhou. Obesity was categorized as non-obesity, general obesity, central obesity, or compound obesity according to established diagnostic criteria. We employed a logistic regression model to assess the relationship between different types of obesity and the risk of dyslipidemia. Additionally, we used the restricted cubic spline model to analyze the association between BMI, WC, and the risk of dyslipidemia. The study included 2030 residents aged 35 or older from Ganzhou, China. The prevalence of dyslipidemia was found to be 39.31%, with an age-standardized prevalence of 36.51%. The highest prevalence of dyslipidemia, 58.79%, was observed among those with compound obesity. After adjusting for confounding factors, we found that the risk of dyslipidemia in those with central and compound obesity was respectively 2.00 (95% CI 1.62–2.46) and 2.86 (95% CI 2.03–4.03) times higher than in the non-obese population. Moreover, the analysis using the restricted cubic spline model indicated a nearly linear association between BMI, WC, and the risk of dyslipidemia. The findings emphasize the significant prevalence of both dyslipidemia and obesity among adults aged 35 and above in Ganzhou, China. Notably, individuals with compound obesity are at a substantially increased risk of dyslipidemia. Therefore, it is crucial to prioritize the use of BMI and WC as screening and preventive measures for related health conditions.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. Methods Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. Results From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. Conclusions Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.