Porous-nanozyme-based colorimetric sensor for rapid detection of kanamycin in foods under neutral condition.

Most colorimetric methods based on nanozymes need to have excellent performance under acidic condition, so they are currently facing some challenges in the field of food hazard detection. Herein, a facile and rapid colorimetric sensor for kanamycin (KAN) detection in foods under neutral condition has been designed using the peroxidase-mimic activity of porous nanozyme like Co3 O4 nanodisk. Further investigations showed that the interaction mechanism between porous Co3 O4 nanodisk and substrates belongs to a ping-pong model, and the inhibition type of KAN on the peroxidase-mimic activity is noncompetitive inhibition. The constructed sensor has good sensitivity for KAN with the limit of 57 nM, and the color changes can be discerned visually when KAN exceeds 0.5 µM. Besides, the colorimetric sensor obtains excellent recovery results in chicken serum, milk, honey, and pork, which shows that the proposed sensing strategy can provide a rapid and convenient detection method for KAN in foods under neutral condition. PRACTICAL APPLICATION: The established sensing strategy can rapidly distinguish whether KAN residue exceeds the permissible level within 10 min, which meets the requirement for on-site monitoring of antibiotics in foods, and also open up a new idea for other hazards detection under neutral condition.

Diabetes remission after a lifestyle-medicine intervention on type 2 diabetes in lean and obese Chinese subjects: a prospective study.

BACKGROUND: Whether diabetes remission still happened among non-obese type 2 diabetes (T2DM) patients with a body mass index (BMI) <25 kg/m2 following lifestyle-medicine interventions was quite necessary to be reported because many diabetes happened with normal or low BMI in China. METHODS: The criteria for subject inclusion: <20 years after T2DM diagnosis, ≥6 months treatment with oral anti-diabetic drugs, without serious complications, and no history of insulin use. They were divided into two groups: the obesity group (BMI ≥25 kg/m2) and the lean group (BMI <25 kg/m2). All subjects received the following lifestyle-medicine interventions: stopping oral anti-diabetic therapy, initiating a low-carbohydrate (contributing by 35-40% to calorie intake) diet for the first month (gradual transition to a normal diet for the next 5 months), participating in resistance and aerobic exercise, and receiving strengthen management. Diabetes remission was defined as glycosylated hemoglobin (A1C) level <6.5% (<48 mmol/mol) after 6 months of not taking any anti-diabetic medications during the lifestyle-medicine intervention. Finally, 125 individuals completed the lifestyle-medicine intervention in the prospective study. The efficacy and safety of lifestyle-medicine intervention were assessed and compared between lean and obese Chinese subjects with T2DM. RESULTS: We found that 64.52% of the T2DM subjects in the obese group and 60.64% of T2DM subjects in the lean group achieved diabetes remission [i.e., an A1C level <6.5% (48 mmol/mol)] without any anti-diabetic medications after the 6-month lifestyle-medicine intervention. Our multiple linear regression analysis showed that decreases in the fasting plasma glucose (FPG) level had the most powerful effect on decreases in the A1C level after the intervention (R2=0.3072). CONCLUSIONS: Lifestyle-medicine interventions may have increased effectiveness in controlling mild T2DM as compared with the oral antidiabetic-based treatment; unexpectedly, there seems no further improvement in lean relative to obese patients. Three in five subjects could achieve diabetes remission though the lifestyle-medicine intervention regardless of whether their BMI was below or above 25 kg/m2.

Lipid transporter LSR1 positively regulates leaf senescence in Arabidopsis.

Senescence is the final stage in the life history of a leaf, whereby plants relocate nutrients from leaves to other developing organs. Recent efforts have begun to focus on understanding the network-based molecular mechanism that incorporates various environmental signals and leaf age information and involves a complex process with the coordinated actions of multiple pathways. Here, we identified a novel participant, named LSR1 (Leaf Senescence Related 1), that involved in the regulation of leaf senescence. Loss-of-function lsr1-1 mutant showed delayed leaf senescence whereas the overexpression of LSR1 accelerated senescence. LSR1 encodes a lipid transfer protein, and the results show that the protein is located in chloroplast and intercellular space. The LSR1 may be involved in the regulation of leaf senescence by transporting lipids in plants.

Influence of white matter lesions on the prognosis of acute cardioembolic stroke without reperfusion therapy.

BACKGROUND: Few studies have investigated the influence of white matter lesions (WMLs) on the prognosis of acute cardioembolic stroke (CES). We aimed to explore the role of WMLs in predicting 3-month prognosis of CES without reperfusion therapy. METHODS: A number of 251 acute CES patients without reperfusion therapy at a single center were retrospectively recruited. The severity of WMLs was evaluated by Fazekas scale and patients were divided into mild WMLs group (188 cases, Fazekas ≤ 2 points) and moderate to severe WMLs group (63 cases, Fazekas ≥ 3 points) accordingly. General data and clinical features of the two groups were compared. Functional outcomes of patients were followed up for 3 months using the modified Rankin scale (mRS) and patients were divided into poor outcome group (mRS ≥ 3) and favorable outcome group (mRS ≤ 2). The effect of WMLs on the prognosis was identified by binary logistic regression. RESULTS: Patients in moderate to severe WMLs group were older (P < 0.001). Also, they had higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) and elevated incidence of asymptomatic cerebral hemorrhage (P = 0.040) and stroke associated pneumonia (P = 0.001) than those in mild WMLs group. At 3 months, there were 100 cases in the poor outcome group. Patients in poor outcome group had higher baseline NIHSS score, increased proportion of moderate to severe WMLs, and elevated incidence of stroke associated pneumonia than those in favorable outcome group (P < 0.001). Binary logistic regression analysis showed that moderate to severe WMLs (odds ratio [OR] = 4.105, 95 % confidence interval [CI] = 1.447-11.646), baseline NIHSS score (OR = 1.368, 95 % CI = 1.240-1.511), and stroke-associated pneumonia (OR = 4.840, 95 %CI = 1.889-12.400) were independent risk factors for poor outcome. CONCLUSIONS: Moderate to severe WMLs is an independent risk factor for prognosis of CES patients without reperfusion therapy.

Porous Co3O4 nanodisks as robust peroxidase mimetics in an ultrasensitive colorimetric sensor for the rapid detection of multiple heavy metal residues in environmental water samples.

The current method for rapid and ultrasensitive detection of multiple heavy metals in environmental water still face challenge. Herein, the porous Co3O4 nanodisks with robust peroxidase-mimicking activity were prepared, and its catalytic activity can be significantly inhibited by the heavy metals like Cd(II), Hg(II), Pb(II) and As, which makes us to establish an ultrasensitive and rapid colorimetric sensor for the detection of multiple heavy metals. Further investigation reveals the anticompetitive inhibition effect of heavy metals on peroxidase-mimicking activity. The colorimetric sensor displays excellent sensitivity and selectivity, and the limits of detection (LOD) for Cd(II), Hg(II), Pb(II) and As are 0.085 µg·L-1, 0.19 µg·L-1, 0.2 µg·L-1 and 0.156 µg·L-1, respectively. Notably, the absorbance variation will be greater than 0.5 as the concentration of heavy metals exceeds 5 µg·L-1, which can be clearly discriminated by the naked eyes. Moreover, the average recovery range of heavy metals in actual water samples is from 86.9% to 98.3%. The above results indicate that the proposed sensor exhibits excellent practical applicability for the rapid and ultrasensitive detection of multiple harmful heavy metals in several environmental water samples, which has potential bright application in protecting the environment and human health.

Facile Colorimetric Nanozyme Sheet for the Rapid Detection of Glyphosate in Agricultural Products Based on Inhibiting Peroxidase-Like Catalytic Activity of Porous Co3O4 Nanoplates.

The rapid and onsite detection of glyphosate herbicides in agricultural products is still a challenge. Herein, a novel colorimetric nanozyme sheet for the rapid detection of glyphosate has been successfully prepared through the physical adsorption of porous Co3O4 nanoplates on a polyester fiber membrane. Glyphosate can specifically inhibit the peroxidase-mimicking catalytic activity of porous Co3O4 nanoplates, thereby the visual detection of glyphosate can be realized by distinguishing the change in the color intensity of the established nanozyme sheet. The prepared nanozyme sheet has good sensitivity and selectivity, with a detection limit of 0.175 mg·kg-1 for glyphosate detection just by the naked eyes. It can effectively detect glyphosate within 10 min, and the color spots can maintain more than 20 min. The nanozyme sheet is not easily affected by the external environment in detection and storage. The merits of the nanozyme sheet facilitate its practical application in the large-scale preliminary screening of glyphosate residues in agricultural products.

Leptin Receptor Deficiency Protects Mice against Chronic Cerebral Hypoperfusion-Induced Neuroinflammation and White Matter Lesions.

Leptin participates in the inflammatory responses in multiple cell types and animal models. Chronic cerebral hypoperfusion (CCH) induces inflammation in the central nervous system (CNS), which acts as one of the main reasons for CCH-induced white matter lesions (WMLs). But whether leptin participates in the pathogenesis of CCH-induced WMLs remains unknown. Therefore, we performed bilateral common carotid artery stenosis (BCAS) to induce CCH on the leptin receptor- (LepR-) deficient db/db mice, aiming to evaluate the possible involvement of leptin in CCH-induced cognitive impairment, WMLs, and neuroinflammation, and further explore the effect of leptin on chronic hypoxia-induced inflammation using the BV2 microglial cell line. After four weeks of BCAS, wild-type mice showed significant working memory deficits, WMLs, activation of microglia and astrocytes, decrease in the number of oligodendrocytes, downregulation of myelin basic protein expression, and increase in the expression of TNF-α and IL-1ß; however, four weeks of BCAS failed to induce significant changes in the LepR-deficient db/db mice but elevated the production of anti-inflammatory cytokines and activated the M2 microglia. We further confirmed that leptin would aggravate the hypoxia-induced proinflammatory cytokine expression in the BV2 microglia cell line. These results suggested that LepR deficiency would protect mice against the CCH-induced cognitive impairment and WMLs by inhibiting glial activation and suppressing proinflammatory responses as well as promoting anti-inflammatory cytokine expression and M2 microglia activation in the white matter.

Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis.

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under hypoxic and/or high-glucose conditions.

Chronic cerebral hypoperfusion (CCH) plays an insidious role in the development of cognitive impairment. Considerable evidence suggests that Diabetes Mellitus (DM) as a vascular risk factor may exacerbate CCH and is closely related to cognitive decline. Dysregulation of autophagy is known to be associated with the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. To elucidate the role of autophagy in CCH- and/or DM-related pathogenesis, mouse neuroblastoma Neuro-2a cells were exposed to hypoxia and/or high glucose for 48 h, mimicking CCH complicated with DM pathologies. Chronic hypoxia reduced cell proliferation and increased levels of cleaved caspase-3, whereas high glucose had no obvious synergistic toxic effect. Accumulation of autophagic vacuoles under hypoxia may be due to both autophagy impairment and induction, with the former accounting for Neuro-2a cell death. Additionally, aberrant accumulation of mitochondria in Neuro-2a cells may be attributed to insufficient BNIP3-mediated mitophagy due to poor interaction between BNIP3 and LC3-II. Despite the lack of a significant cytotoxic effect of high glucose under our experimental conditions, our data indicated for the first time that impaired autophagy degradation and inefficient BNIP3-mediated mitophagy may constitute mechanisms underlying neuronal cell damage during chronic hypoxia.

The Role of Autophagy in the Correlation Between Neuron Damage and Cognitive Impairment in Rat Chronic Cerebral Hypoperfusion.

Pathological changes and cognitive impairment caused by chronic cerebral hypoperfusion (CCH) have been previously reported. However, how these changes progress remains unclear. Additionally, there are few studies regarding the mechanism underlying the involvement of autophagy in these processes. Two-step bilateral common carotid artery occlusion (BCCAO) was performed to replicate CCH in Sprague Dawley rats. The animals were divided into seven groups, including a sham group and 2-, 4-, 8-, 12-, 16-, and 20-week BCCAO groups (n = 7 per group). Five additional rats were used to monitor cerebral blood fluid (CBF) changes via laser speckle contrast imaging (LSCI). We tested for cognitive changes and pathological changes, including neuronal injury, white matter lesions, and ß-Amyloid (Aß) deposition, via acknowledged methods. Autophagy was analyzed via western blotting and immunohistochemistry. Cognitive impairment appeared beginning at 8 weeks after BCCAO despite improvement in CBF. Neuronal damage began at 8 weeks in the hippocampal CA1 region and at 4 weeks in the cortex. White matter injury was detected in all BCCAO groups. Intracellular Aß accumulation occurred earlier than extracellular plaque formation. The levels of autophagy-related proteins (Beclin-1, light chain 3B, and P62) increased beginning at 2 weeks in the cortex and at 4 weeks in the hippocampus and remained elevated throughout the remainder of the study period. Despite recovery of CBF, autophagy dysfunction occurred early after CCH and played an important role in neuronal deterioration, cognitive decline, and intracellular Aß aggregation.

Cinepazide Maleate Improves Cognitive Function and Protects Hippocampal Neurons in Diabetic Rats with Chronic Cerebral Hypoperfusion.

To determine the combined effect of type 2 diabetes (T2D) and chronic cerebral hypoperfusion (CCH) on learning and spatial memory, we developed a rat model of CCH by permanent occlusion of bilateral common carotid arteries (2-vessel occlusion (2VO)) in high-fat diet (HFD)-fed rats injected with low-dose streptozotocin (STZ). Furthermore, we examined the effect of cinepazide maleate (CM) on cognitive deficits and brain damage in this rat model. Rats were maintained on HFD for 6 weeks and then injected with 35 mg/kg STZ to induce T2D. Sham or 2VO surgery was performed in non-diabetic or diabetic (DM) rats to obtain four groups: blank, DM, CCH, and DM-CCH groups. Cognitive function was tested by the Morris water maze (MWM) test. To determine the effects of the vasodilator cinepazide maleate (CM) on cognitive deficits and brain damage, DM-CCH rats were administered with 10 mg/kg CM or saline daily for 14 d. Neuronal damage in DM-CCH rats was associated with increased expression of glial fibrillary acidic protein (GFAP) and ß-secretase 1 (BACE1), but decreased expression of choline acetyltransferase (ChAT). Moreover, the levels of all these proteins were significantly alleviated by CM treatment. These results suggest that T2D exacerbated CCH-induced brain damage and cognitive impairment, and CM ameliorated these effects.

Relationships between CETP genetic polymorphisms and Alzheimer's disease risk: a meta-analysis.

This meta-analysis was performed to evaluate the relationships between single-nucleotide polymorphisms in the CETP gene and the risk of Alzheimer's disease (AD). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through October 1, 2013, without language restrictions. Nine case-control studies with a total of 2172 AD patients and 8017 healthy controls were involved in this meta-analysis. Two common polymorphisms (rs708272 T>C and rs5882 A>G) in the CETP gene were assessed. Our meta-analysis results showed that CETP rs5882 A>G polymorphism might increase the risk of AD (A allele vs. G allele: odds ratio [OR]=1.11, 95% confidence interval [95% CI]=1.02-1.21, p=0.014; AA+AG vs. GG: OR=1.28, 95% CI=1.07-1.52, p=0.006; AA vs. GG: OR=1.32, 95% CI=1.10-1.70, p=0.003; AA vs. AG: OR=1.25, 95% CI=1.03-1.50, p=0.020; respectively). However, we found no correlations of CETP rs708272 T>C polymorphism with AD risk (all p>0.05). Subgroup analysis by ethnicity suggested positive associations between CETP rs5882 A>G polymorphism and an increased risk of AD among Caucasians (A allele vs. G allele: OR=1.10, 95% CI=1.01-1.21, p=0.014; AA+AG vs. GG: OR=1.34, 95% CI=1.06-1.69, p=0.015; AA vs. GG: OR=1.35, 95% CI=1.07-1.70, p=0.011; respectively), but not among Asians (all p>0.05). No associations were found between CETP rs708272 T>C polymorphism and AD risk among both Asians and Caucasians (all p>0.05). Our findings provide empirical evidence that CETP rs5882 A>G polymorphism may contribute to susceptibility to AD, especially among Caucasians. However, CETP rs708272 T>C polymorphism does not seem to be an important determinant in the pathogenesis of AD.

Requirement for both receptor-operated and store-operated calcium entry in N-formyl-methionine-leucine-phenylalanine-induced neutrophil polarization.

Tissue penetration of neutrophils is a key process in many inflammatory diseases. In response to inflammatory stimuli such as N-formyl-methionine-leucine-phenylalanine (fMLP), neutrophils polarize and migrate towards the chemotactic gradient of the stimulus. Elevated intracellular Ca(2+) concentration is known to play a critical role in neutrophil polarization and migration; however, the exact mechanism remains elusive. Here, we demonstrated that fMLP stimulation caused not only store-operated calcium entry (SOCE), but also receptor-operated calcium entry (ROCE) in neutrophils by using both pharmacological and neutralizing monoclonal antibody approaches. We also investigated neither Rac2 nor Cdc42 activation could take place if either SOCE or ROCE was inhibited. This study thus provides the first evidence for coordination of Ca(2+) influx by SOCE and ROCE to regulate neutrophil polarization.

Store-operated Ca2+ entry (SOCE) plays a role in the polarization of neutrophil-like HL-60 cells by regulating the activation of Akt, Src, and Rho family GTPases.

Neutrophil polarization is a basic activity involved in the innate immune response, and it may be initiated by extracellular Ca(2+) entry, a process primarily mediated through store-operated Ca(2+) entry (SOCE). Yet, the mechanisms by which SOCE participates in cell polarization remain unclear. We hypothesized that Akt- and Src-dependent pathways, traditionally linked to neutrophil polarization, may interact with SOCE in this event. In this study, SKF96365 and 2-APB, inhibitors of SOCE as proved by their inhibition on Mn(2+) influx, were observed to inhibit the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced influx of Ca(2+), the activation of Akt, Src, Rac1, Rac2, and Cdc42, and the polarization of differentiated HL-60 (dHL-60) cells. Downregulation of stromal interaction molecule 1 (STIM1), a Ca(2+) sensor identified to induce SOCE, by siRNA led to decreases in the following indexes: Ca(2+) entry, activation of Akt, Src, Rac2 (rather than Rac1) and Cdc42, and fMLP-induced polarization. This study suggests that SOCE might be the predominant form of Ca(2+) entry involved in the regulation of cell polarization, and it may act through the Akt/Src/Rac pathways, as modeled in dHL-60 cells. It also suggests that STIM1 is a key modulator of cell polarization, potentially serving as a target for the designation of anti-immune deficiency therapies.

AKT-mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells.

OBJECTIVES: Neutrophil polarization is critical for the inflammatory response. AKT is a serine/threonine protein kinase and has been implicated in cell migration. However, it is not completely clear whether AKT affects neutrophil polarization. In this study, we tested the hypothesis that AKT regulates the polarization of neutrophil-like differentiated HL-60 cells (dHL-60) in response to fMLP. METHODS: HL-60 cells were differentiated into dHL-60 by incubation in medium containing 1.3 % DMSO for up to 6 days. Polarization of dHL-60 cells and primary human neutrophils were measured by Zigmond chamber. Phospho-Akt was analyzed by immunofluorescence and Western blot analysis. F-actin polymerization was detected by Rhodamine-Phalloidine staining. Rac2 activation was evaluated using GST Pull-down assay. RESULTS: We found that changes in the rate of cell polarization were consistent with the changes in AKT phosphorylation levels during HL-60 cell differentiation in response to fMLP. Moreover, cell polarization and AKT phosphorylation were reduced in fMLP-stimulated dHL-60 cells pretreated with the PI3 kinase inhibitors or the AKT inhibitors, which was confirmed in the primary human neutrophils. The AKT inhibitors altered fMLP-induced F-actin polymerization. Rac2 GTPases was also decreased by the AKT inhibitors in fMLP-stimulated dHL-60 cells. CONCLUSION: This study demonstrates that AKT activation plays a crucial role in dHL-60 cell polarization.