Differential mechanisms underlie trace and delay conditioning in Drosophila.

Two forms of associative learning-delay conditioning and trace conditioning-have been widely investigated in humans and higher-order mammals1. In delay conditioning, an unconditioned stimulus (for example, an electric shock) is introduced in the final moments of a conditioned stimulus (for example, a tone), with both ending at the same time. In trace conditioning, a 'trace' interval separates the conditioned stimulus and the unconditioned stimulus. Trace conditioning therefore relies on maintaining a neural representation of the conditioned stimulus after its termination (hence making distraction possible2), to learn the conditioned stimulus-unconditioned stimulus contingency3; this makes it more cognitively demanding than delay conditioning4. Here, by combining virtual-reality behaviour with neurogenetic manipulations and in vivo two-photon brain imaging, we show that visual trace conditioning and delay conditioning in Drosophila mobilize R2 and R4m ring neurons in the ellipsoid body. In trace conditioning, calcium transients during the trace interval show increased oscillations and slower declines over repeated training, and both of these effects are sensitive to distractions. Dopaminergic activity accompanies signal persistence in ring neurons, and this is decreased by distractions solely during trace conditioning. Finally, dopamine D1-like and D2-like receptor signalling in ring neurons have different roles in delay and trace conditioning; dopamine D1-like receptor 1 mediates both forms of conditioning, whereas the dopamine D2-like receptor is involved exclusively in sustaining ring neuron activity during the trace interval of trace conditioning. These observations are similar to those previously reported in mammals during arousal5, prefrontal activation6 and high-level cognitive learning7,8.

A mitochondrial RNA processing protein mediates plant immunity to a broad spectrum of pathogens by modulating the mitochondrial oxidative burst.

Mitochondrial function depends on the RNA processing of mitochondrial gene transcripts by nucleus-encoded proteins. This posttranscriptional processing involves the large group of nuclear-encoded pentatricopeptide repeat (PPR) proteins. Mitochondrial processes represent a crucial part in animal immunity, but whether mitochondria play similar roles in plants remains unclear. Here, we report the identification of RESISTANCE TO PHYTOPHTHORA PARASITICA 7 (AtRTP7), a P-type PPR protein, in Arabidopsis thaliana and its conserved function in immunity to diverse pathogens across distantly related plant species. RTP7 affects the levels of mitochondrial reactive oxygen species (mROS) by participating in RNA splicing of nad7, which encodes a critical subunit of the mitochondrial respiratory chain Complex I, the largest of the four major components of the mitochondrial oxidative phosphorylation system. The enhanced resistance of rtp7 plants to Phytophthora parasitica is dependent on an elevated mROS burst, but might be independent from the ROS burst associated with plasma membrane-localized NADPH oxidases. Our study reveals the immune function of RTP7 and the defective processing of Complex I subunits in rtp7 plants resulted in enhanced resistance to both biotrophic and necrotrophic pathogens without affecting overall plant development.

A Compound Heterozygosis of Two Novel Mutations in vWF Exacerbates vWD in a Chinese Pedigree.

BACKGROUND: von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD. METHODS: We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing. RESULTS: The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTO-CETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF: NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF: NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges. CONCLUSIONS: We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD.

Relationship between slow-wave sleep and serum γ-glutamine transaminase in non-obese men with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a disease characterized with intermittent hypoxia and sleep fragmentation. Obesity and gender are major risk factors for the onset of OSAHS. Previous studies on obese men with OSAHS have been performed, while few studies on non-obese men with OSAHS have been carried out. The purpose of this study was to explore the clinical characteristics of polysomnography and blood biochemical indexes in non-obese men with OSAHS and to identify the possible influencing factors. METHODS: This retrospective study included patients with OSAHS who underwent polysomnography in our hospital. General clinical data such as overnight polysomnography and biochemical indicators were recorded. The patients were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSAHS and severe OSAHS. The differences in biochemical parameters such as the levels of γ-glutamine transaminase (GGT), triglyceride (TG), glucose (GLU), and sleep structure parameters such as N1, N2, slow-wave sleep (SWS), and rapid eye movement (REM) sleep were compared and analyzed. Spearman correlation analysis and logistic regression were used to identify the risk factors of non-obese men with OSAHS. ROC curves were used to evaluate the predictive ability of SWS and GGT on disease severity. RESULTS: Of 94 non-obese men with OSAHS, 49 had mild to moderate OSAHS and 45 had severe OSAHS. Our data suggested that the levels of low oxygen saturation (L-SaO2), mean oxygen saturation (M-SaO2), SWS, and GGT were significantly changed in the mild to moderate OSAHS group compared with the severe group (p < 0.05). For patients with OSAHS, the proportion of SWS in the group with severe OSAHS was higher than that in the mild to moderate group (p < 0.05), and the serum GGT enzyme levels were significantly elevated in the severe group compared to the mild to moderate group (p < 0.05). Using logistic regression analyses, our data revealed that both SWS and GGT enzyme levels were independent risk factors for AHI (p < 0.05). In addition, the results of correlation analysis indicated that SWS was related to triglyceride (TG), total cholesterol (TC), apolipoprotein E (APOE), and triglyceride glucose (TyG) index (p < 0.05); GGT was related to TG, TC, APOE, and TyG index (p < 0.05). Furthermore, SWS was independently associated with GGT (p < 0.05). The area under the ROC curve plotted with the combined coefficient of SWS and serum GGT was 0.728, which was predictive of the disease severity. CONCLUSIONS: These results suggest that SWS and GGT are independent associated factors of the severity of the disease. However, TyG index was not an independent associated factor of the severity of disease in non-obese men with OSAHS. In addition, SWS and GGT were negatively correlated. SWS combined with serum GGT may be predictive of the severity of the disease. This study may have added to our understanding of the pathogenesis of OSAHS in non-obese men.

Correlation between cognitive impairment and serum markers in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Previous studies have revealed that sleep structure and hypoxemia are two important environmental factors for cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that the pathophysiological mechanisms between these two factors may also be involved in cognitive impairment in patients with OSAHS. Previous studies have suggested that alterations in serum glucose and lipid metabolism, inflammatory responses, and astrocyte markers not only contribute to sleep structural disorders in OSAHS but also affect the occurrence and development of this disease. Therefore, we hypothesized that alterations in the abovementioned indicators may be involved in cognitive impairment in OSAHS. Additionally, obesity is an important risk factor for OSAHS. This study therefore aimed to explore the correlation between serum indicators and cognitive impairment in patients with OSAHS. METHODS: Patients with OSAHS who underwent polysomnography in our hospital were recruited in this study. The overall cognitive function of patients were evaluated using the Mini mental State Examination (MMSE). Blood biochemical indicators such as glucose (GLU), triglycerides (TG), and triglyceride glucose (TyG) index were measured. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum glucagon-like peptide-1 receptor (GLP-1R), fibroblast growth factor 21 (FGF21), S100 calcium binding protein B (S100B), brain derived neurotrophic factor (BDNF), inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Spearman correlation analysis was used to determine if the indicator was related to cognitive function, and backward linear regression analysis was used to identify the main risk factors for cognitive impairment in non-obese and obese patients with OSAHS. RESULTS: Among 34 patients, 19 were non-obese and 15 were obese. Obese patients exhibited higher AHI compared to non-obese individuals, and the difference was statistically significant (p < 0.05). In non-obese patients, Spearman correlation analysis revealed a negative correlation between serum GLU, IL-4, and MMSE scores (p < 0.05); IL-6 was positively correlated with MMSE (p < 0.05). In addition, GLU and IL-6 were independently correlated with MMSE in non-obese patients (p < 0.05). In obese patients, serum TG and TyG were positively correlated with MMSE scores (p < 0.05); age, BMI, and IL-4 were negatively correlated with MMSE scores (p < 0.05). In addition, age and IL-4 were independently correlated with MMSE in obese patients (p < 0.05). CONCLUSIONS: Our data suggested that GLU and IL-6 were independently correlated with cognitive impairment in non-obese patients with OSAHS; age and IL-4 were independently correlated with cognitive impairment in obese patients. Early detection of this difference in heterogeneity may provide theoretical support for future investigations in prevention and treatment of cognitive impairment in patients with OSAHS.

A dPCR-NIPT assay for detections of trisomies 21, 18 and 13 in a single-tube reaction-could it replace serum biochemical tests as a primary maternal plasma screening tool?

BACKGROUND: The next generation sequencing (NGS) based non-invasive prenatal test (NIPT) has outplayed the traditional serum biochemical tests (SBT) in screen of fetal aneuploidies with a high sensitivity and specificity. However, it has not been widely used as a primary screen tool due to its high cost and the cheaper SBT is still the choice for primary screen even with well-known shortages in sensitivity and specificity. Here, we report a multiplex droplet digital PCR NIPT (dPCR-NIPT) assay that can detect trisomies 21, 18 and 13 (T21, T18 and T13) in a single tube reaction with a better sensitivity and specificity than the SBT and a much cheaper price than the NGS-NIPT. METHODS: In this study, the dPCR-NIPT assay's non-clinical characteristics were evaluated to verify the cell free fetal DNA (cffDNA) fraction enrichment efficiencies, the target cell free DNA (cfDNA) concentration enrichment, the analytical sensitivity, and the sample quality control on the minimum concentration of cfDNA required for the assay. We validated the clinical performance for this assay by blindly testing 283 clinical maternal plasma samples, including 36 trisomic positive samples, from high risk pregnancies to access its sensitivity and specificity. The cost effectiveness of using the dPCR-NIPT assay as the primary screen tool was also analyzed and compared to that of the existing contingent strategy (CS) using the SBT as the primary screen tool and the strategy of NGS-NIPT as the first-tier screen tool in a simulating situation. RESULTS: For the non-clinical characteristics, the sample processing reagents could enrich the cffDNA fraction by around 2 folds, and the analytical sensitivity showed that the assay was able to detect trisomies at a cffDNA fraction as low as 5% and the extracted cfDNA concentration as low as 0.2 ng/µL. By testing the 283 clinical samples, the dPCR-NIPT assay demonstrated a detection sensitivity of 100% and a specificity of 95.12%. Compared to the existing CS and the NGS-NIPT as the first-tier screen strategy, dPCR-NIPT assay used as a primary screen tool followed by the NGS-NIPT rescreen is the most economical approach to screen pregnant women for fetal aneuploidies without sacrificing the positive detection rate. CONCLUSION: This is the first report on a dPCR-NIPT assay, consisting of all the necessary reagents from sample processing to multiplex dPCR amplification, can detect T21, T18 and T13 in a single tube reaction. The study results reveal that this assay has a sensitivity and specificity superior to the SBT and a cost much lower than the NGS-NIPT. Thus, from both the test performance and the economic benefit points of views, using the dPCR-NIPT assay to replace the SBT as a primary screen tool followed by the NGS-NIPT rescreen would be a better approach than the existing CS for detection of fetal aneuploidies in maternal plasma.

Gas-Sensing Property of TM-MoTe2 Monolayer towards SO2, SOF2, and HF Gases.

Detecting the characteristic decomposition products (SO2, SOF2, and HF) of SF6 is an effective way to diagnose the electric discharge in SF6-insulated equipment. Based on first-principles calculations, Au, Ag, and Cu were chosen as the surface modification transition metal to improve the adsorption and gas-sensing properties of MoTe2 monolayer towards SO2, SOF2, and HF gases. The results show that Au, Ag, and Cu atoms tend to be trapped by TH sites on the MoTe2 monolayer, and the binding strength increases in the order of Ag < Au < Cu. In gas adsorption, the moderate adsorption energy provides the basis that the TM-MoTe2 monolayer can be used as gas-sensing material for SO2, SOF2, and HF. The conductivity of the adsorption system changes significantly. The conductivity decreases upon gases adsorption on TM-MoTe2 monolayer, except the conductivity of Ag-MoTe2 monolayer increases after interacting with SOF2 gas.

Potential mechanisms of cerebrovascular diseases in COVID-19 patients.

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer.

BACKGROUND: Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. RESULTS: Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. CONCLUSIONS: These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. GRAPHIC ABSTARCT.

Serum metabolomics of end-stage renal disease patients with depression: potential biomarkers for diagnosis.

BACKGROUND: End-stage renal disease (ESRD) is the final stage during the development of renal failure. Depression is the most common psychiatric disorder in patients with ESRD, which in turn aggravates the progression of renal failure, however, its underlying mechanism remains unclear. This study aimed to reveal the pathogenesis and to discover novel peripheral biomarkers for ESRD patients with depression through metabolomic analysis. METHODS: Ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) was used to explore changes of serum metabolites among healthy controls, ESRD patients with or without depression. The differential metabolites between groups were subjected to clustering analysis, pathway analysis, receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 57 significant serum differential metabolites were identified between ESRD patients with or without depression, which were involved in 19 metabolic pathways, such as energy metabolism, glycerolipid metabolism, and glutamate-centered metabolism. Moreover, the area under the ROC curve of gentisic acid, uric acid, 5-hydroxytryptamine, 2-phosphoglyceric acid, leucyl-phenylalanine, propenyl carnitine, naloxone, pregnenolone, 6-thioxanthene 5'-monophosphate, hydroxyl ansoprazole, zileuton O-glucuronide, cabergoline, PA(34:2), PG(36:1), probucol and their combination was greater than 0.90. CONCLUSIONS: Inflammation, oxidative stress and energy metabolism abnormalities, glycerolipid metabolism, and glutamate-centered metabolism are associated with the pathogenesis of ESRD with depression, which may be promising targets for therapy. Furthermore, the identified differential metabolites may serve as biomarkers for the diagnosis of ESRD patients with depression.

Dual-Channel Luminescent Signal Readout Strategy for Classifying Aprotic/Protic Polar Organic Medium and Naked-Eye Monitoring of Water in Organic Solvents.

Developing a convenient and rapid detection method for water is greatly desirable in the field of chemical industry. Herein, we present a simple and effective strategy combining a fluorescence sensor and a one-to-two fluorescence colorimetric logic operation to monitor water in a wide range of organic media and classify aprotic/protic polar solvents. The dual-emitting luminescent detector was prepared by incorporating a fluorescent dye Rhodamine 6G (R6G) with strong green light emission within a red light-emitting Eu-metal-organic framework (MOF) through the "bottle around ship" method. R6G@Eu-MOF displays completely different fluorescence response behaviors to various organic solvents. Thus, when one made use of the intensity ratio of different fluorescence emission centers, a 3D decoded map was proposed to reliably and effectively distinguish different aprotic/protic polar solvents. Moreover, R6G@Eu-MOF exhibited two different ratiometric sensing modes when detecting water in aprotic/protic polar solvents due to the hydrogen bonding interaction, that is ratiometry with one reference signal or two reversible signal changes. Furthermore, using water content as the input signal and two kinds of fluorescence emission as the output signals, a one-to-two logic gate system was constructed, making it possible to develop an intelligence system for water detection. Overall, we demonstrated for the first time that R6G@Eu-MOF could serve as an efficient platform for tracing water in organic media and distinguishing protic/aprotic polar organic solvents.

Copper Ion Fluorescent Probe Based on Zr-MOFs Composite Material.

In this work, a novel and effective ratio fluorescent porphyrin metal-organic framework (MOF) probe by encapsulating UiO-66(OH)2 into the porphyrin MOF (PCN-224) was prepared, showing the excellent fluorescence performance in detecting Cu2+. In this probe, the signal from the green-emission UiO-66(OH)2 encapsulated in PCN-224 was deemed as an effective reference, thus affording an effective built-in correction in complex environmental effects. The red-emission PCN-224 contained the active site for detecting Cu2+. At the same time, Cu2+ can selectively quench the fluorescence intensity of PCN-224. The ratiometric probe therefore gave an effective and reliable Cu2+ determination platform with an LOD value as low as 0.068 nM. This LOD result was better than the Cu2+ concentration limitation in drinking water regulated by World Health Organization (WHO) and reported by some other methods. This provides a simple new sensor for rapidly detecting copper ions, which can be further expanded in various environmental and biological analysis tasks.

Leek-derived codoped carbon dots as efficient fluorescent probes for dichlorvos sensitive detection and cell multicolor imaging.

A biomass nitrogen and sulfur codoped carbon dots (NS-Cdots) was prepared by a simple and clean hydrothermal method using leek, and was employed as efficient fluorescent probes for sensitive detection of organophosphorus pesticides (OPs). The leek-derived NS-Cdots emitted blue fluorescence, but was quenched by H2O2. Due to acetylcholinesterase/choline oxidase-based cascade enzymatic reaction that produces H2O2 and the inhibition effect of OPs on acetylcholinesterase activity, a NS-Cdots-based fluorescence "off-on" method to detect OPs-dichlorvos (DDVP) was developed. More sensitivity and wider linear detection range were achieved from 1.0 × 10-9 to 1.0 × 10-3 M (limit of detection = 5.0 × 10-10 M). This developed method was applied to the detection of DDVP in Chinese cabbage successfully. The average recoveries were in the range of 96.0~104.0% with a relative standard deviation of less than 3.3%. In addition, the NS-Cdots fluorescent probes were also employed successfully in multicolor imaging of living cells, manifesting that the NS-Cdots fluorescent probes have great application potential in agricultural and biomedical fields. Graphical Abstract.

P,N Codoped carbon dots as an efficient "off-on" fluorescent probe for lipoic acid detection and its cellular dual-color imaging.

A facile single hydrothermal method was developed to synthetize P,N codoped carbon dots (P,N/CDs), which show strong and stable fluorescence, good water solubility, low toxicity and good biocompatibility. Hence, a novel and efficient "off-on" P,N/CDs fluorescent probe was developed for the highly sensitive detection of lipoic acid (LA) for the first time. The fluorescence of the P,N/CDs was quenched by Cu2+ forming a P,N/CDs-Cu2+ complex, which acted as the "off" process, but Cu2+ could be removed by LA, due to stronger chelating between LA and Cu2+, forming a more stable complex, which recovered the fluorescence of the P,N/CDs, in order to achieve the "on" process. Under optimal conditions, the concentration of LA and the increased fluorescence intensity of the P,N/CDs-Cu2+ complex displayed a good linear relationship within the range of 0.05-28 µM, with a detection limit (S/N = 3) of 0.02 µM. The established "off-on" fluorescent probe was successfully applied to the analysis of LA in urine samples. The average recoveries were in the range of 98.3-101.5%, with a relative standard deviations of less than 3.1%. In addition, the P,N/CDs were also successfully applied to cellular dual-color imaging of live T24 cells. The results show that the P,N/CDs have great application potential in clinical diagnosis, bioassay and bioimaging. Graphical abstract.

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes.

BACKGROUND/AIMS: HIF-1α is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1α contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1α in regulating neurological injury evoked by intracerebral hemorrhage (ICH) through its downstream product, namely vascular endothelial growth factor (VEGF). In particular, we examined the effects of diabetic hyperglycemia on HIF-1α response in the processing of ICH. METHODS: ELISA was used to measure HIF-1α and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. RESULTS: HIF-1α and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1α and VEGF were attenuated in diabetic rats (P<0.05 vs. non-diabetic rats) as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (P<0.05 vs. non-diabetic rats). Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. CONCLUSION: HIF-1α activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1α is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1α and VEGF pathway for neuronal dysfunction and vulnerability related to ICH.

Analysis of risk factors of ST-segment elevation myocardial infarction in young patients.

BACKGROUND: Acute myocardial infarction (AMI) is often present in old populations and rare in young people. Its incidence significantly increased recent years. The mechanism and disease course of AMI in young people are probably different from that in old population. The aim of this study was to analyze clinical risk factors of STEMI in young patients. METHODS: Data was collected from consecutive patients ≤ 44 years of age (young; n = 86) and 60-74 years of age (old; n = 65) diagnosed with STEMI, and 79 young age-matched patients without coronary artery disease (CAD), hospitalized between January 2009 and June 2013. RESULTS: The young STEMI group had a significantly higher proportion of males (88.37 vs. 53.16%; P < 0.01), smokers (82.56 vs. 49.37%; P < 0.01) and patients with a family history of early CAD (54.65 vs. 32.91%; P < 0.05) than age-matched controls. Young STEMI patients also had significantly higher levels of fasting blood sugar (6.39 vs. 5.25 mmol/L; P < 0.001), glycated hemoglobin (HbA1c) (6.26 vs. 5.45%; P < 0.05), total cholesterol (5.14 vs. 4.65 mmol/L, P < 0.05), and fibrinogen (Fib) (3.39 vs. 2.87; P < 0.01). Compared with the old STEMI group, young STEMI patients had significantly higher proportions of males (88.37 vs. 63.08%; P < 0.01) smokers (82.56 vs. 41.54%; P < 0.01), and those with a family history of early CAD (54.65 vs. 18.46%; P < 0.01). Young STEMI patients also lower Fib (3.39 vs. 3.88 g/L; P < 0.01), less frequent occurrence of angina pectoris before STEMI (13.95 vs. 29.23%; P < 0.05) compared with the old STEMI group. Logistic regression analysis indicated that male sex (OR = 5.891), smoking (OR = 3.500), family history of early CAD (OR = 3.194), Fib (OR = 2.414) and HbA1c (OR = 1.515) are associated with STEMI in young patients. CONCLUSION: In addition to previously recognized risk factors (male sex, smoking and family history of early CAD), Fib and HbA1c are associated with STEMI in individuals ≤ 44 years of age without antecedent angina pectoris.

Sialic acid metabolism of oral bacteria and its potential role in colorectal cancer and Alzheimer's disease.

Sialic acid metabolism in oral bacteria is a complex process involving nutrient acquisition, immune evasion, cell surface modification, and the production of metabolites that contribute to bacterial persistence and virulence in the oral cavity. In addition to causing various periodontal diseases, certain oral pathogenic bacteria, such as Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum, can induce inflammatory reactions and influence the immunity of host cells. These associations with host cells are linked to various diseases, particularly colorectal cancer and Alzheimer's disease. Sialic acid can be found in the host oral mucosa, saliva, or food residues in the oral cavity, and it may promote the colonization of oral bacteria and contribute to disease development. This review aims to summarize the role of sialic acid metabolism in oral bacteria and discuss its effect on the pathogenesis of colorectal cancer and Alzheimer's disease.

Low-temperature CO preferential oxidation in H2-rich stream over Indium modified Pd-Cu/Al2O3 catalyst.

The impact of Indium (In) doping upon the catalytic performance of Pd-Cu/Al2O3 for carbon monoxide preferential oxidation (CO-PROX) in hydrogen (H2) rich atmosphere at low temperature has been studied. A series of catalysts with extremely low palladium (Pd) loading (0.06 wt%) are synthesized by the facile co-impregnation method. When the In/copper (Cu) atomic ratio equals 0.25, Pd-Cu-In0.25/Al2O3 can keep 40% CO conversion and 100% carbon dioxide (CO2) selectivity at least 120 min at 30 °C, which is significantly superior to the catalytic performance of Pd-Cu/Al2O3. The elaborate characterization findings reveal that the added In species to Pd-Cu/Al2O3 causes Indium oxide (In2O3) to generate, which produces the interaction of In2O3 with Pd-Cu/Al2O3, further promoting the dispersion of copper chloride hydroxide (Cu2Cl(OH)3). Moreover, the modification of In facilitates the re-oxidation of Pd0 to Pd+ through reducing the formation of palladium hydride (PdHx) during the CO-PROX reaction. Meanwhile, the addition of In leads to the decrease of Cu+ electron cloud density, making it easier to be oxidized to Cu2+. Collectively, the easy re-oxidation of Pd0 and Cu+ is favorable to fulfill the Wacker cycle between Pd and Cu species, thus improving the catalytic performance for CO-PROX.