Effects of different postharvest drying processes on flavonoid content and enzymatic activity of Styphnolobium japonicum (L.) Schott flowers for industrial and medicinal use.

Traditionally, fresh S. japonicum flowers (SJF) and S. japonicum flowers buds (SJFB) are dried prior to further processing and use. Here, we investigated the ways in which drying techniques, including sun drying (SD), steam drying (STD), microwave drying (MD), hot air drying (HAD, 40 °C, 60 °C, 80 °C, 100 °C), and freeze drying (FD), alter the flavonoid composition of freshly-harvested SJF and SJFB. The flavonoid content of dried samples was determined by Ultra High Performance Liquid Chromatography-Diode Array Detector (UPLC-DAD). Overall, different drying techniques had significantly different effects on the RU content, ranging from 10.63 % (HAD-80 °C) to 34.13 % (HAD-100 °C) in SJF and from 18.91 % (HAD-100 °C) to 29.16 % (HAD-40 °C) and 30.53 % (SD) in SJFB. To clarify the mechanism by which drying affects the RU content of S. japonicum flowers, we studied the activity of a rutin-hydrolyzing enzyme (RHE) isolated from SJF and SJFB using multiple separation and assay methods. According to the Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) results, the apparent molecular weight of the purified RHE was approximately 38 kDa. According to UPLC-DAD, RHE catalyzes the production of quercetin (QU) from rutin (RU), but not from other flavonoid glycosides. Drying fresh SJF and SJFB at low and high temperatures can inhibit RHE activity and prevent RU hydrolysis. Therefore, subjecting freshly-harvest SJF to HAD-100 °C, and freshly-harvest SJFB to SD or HAD-40 °C, can greatly increase the RU content. In particular, HAD is viable for large-scale application due to its simplicity and industrial feasibility.

Investigation of piezoelectric printing devices for oil-free and on-demand picolitre monodisperse droplet generation.

Picolitre monodisperse droplet printing technology has important applications in biochemistry, such as accounting for quantitative analysis and single-cell analysis, and can be used for parallel high-throughput analysis of biomarkers and chemicals. However, commonly used droplet generation devices require complex control systems or customised microfluidic chips, making them costly and difficult for researchers to operate. Additionally, generating picolitre monodisperse droplets with microfluidic devices necessitates the introduction of an oil phase to block and separate the liquid. This requirement can reduce the throughput of the target droplets and cause cell contamination, hindering the adoption of this technology. By employing a common 1-mm-diameter capillary in the laboratory in combination with a piezoelectric transducer, we have achieved on-demand picolitre droplet printing of less than 100 pL in an oil-free environment. The device was found to be biocompatible with K562 cells. This approach is less costly, offers greater operational freedom, and is easier to integrate with other downstream assay modules or even handheld cell-printing devices. This study holds great potential for application in areas such as single-cell analysis, cell sampling, and pharmaceutical analysis.

Dentate Gyrus Morphogenesis is Regulated by an Autism Risk Gene Trio Function in Granule Cells.

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.

A microchip gas chromatography column assembly with a 3D metal printing micro column oven and a flexible stainless-steel column.

In this work, a microchip gas chromatography (GC) column assembly utilizing a three-dimensional (3D) printed micro oven and a flexible stainless steel capillary column was developed. The assembly's performance and separation capabilities were characterized. The key components include a 3D printed aluminum plate (7.50 × 7.50 × 0.16 cm) with a 3-meter-long circular spiral channel, serving as the oven, and the column coiled on the channel with an inner diameter of 320 µm and a stationary phase of OV-1. A heating ceramic plate was affixed on the opposite side of the plate. The assembly weighed 40.3 g. The design allows for easy disassembly, or stacking of heating devices and columns, enabling flexibility in adjusting column length. When using n-C13 as the test analyte at 140 °C, a retention factor (k) was 8.5, and 7797 plates (2599 plates/m) were obtained. The assembly, employing resistance heating, demonstrated effective separation performance for samples containing alkanes, aromatics, alcohols and ketones, with good reproducibility. The reduction in theoretical plates compared to oven heating was only 2.95 %. In the boiling point range of C6 to C18, rapid temperature programming (120 °C/min) was achieved with a power consumption of 119.512 W. The assembly was successfully employed to separate benzene series compounds, gasoline and volatile organic compounds (VOCs), demonstrating excellent separation performance. This innovative design addresses the challenges of the complexity and low repeatability of the fabrication process and the high cost associated with microchip columns. Furthermore, its versatility makes it suitable for outdoor analysis applications.

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy.

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.

Differential Impact In Vivo of Pf4-ΔCre-Mediated and Gp1ba-ΔCre-Mediated Depletion of Cyclooxygenase-1 in Platelets in Mice.

BACKGROUND: Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1-derived thromboxane A2. Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte/platelet ablation of Cox-1 in mice. However, Pf4-ΔCre displays ectopic expression outside the megakaryocyte/platelet lineage, especially during inflammation. The use of the Gp1ba (glycoprotein 1bα) Cre promises a more specific, targeted approach. METHODS: To evaluate the role of Cox-1 in platelets, we crossed Pf4-ΔCre or Gp1ba-ΔCre mice with Cox-1flox/flox mice to generate platelet Cox-1-/- mice on normolipidemic and hyperlipidemic (Ldlr-/-; low-density lipoprotein receptor) backgrounds. RESULTS: Ex vivo platelet aggregation induced by arachidonic acid or adenosine diphosphate in platelet-rich plasma was inhibited to a similar extent in Pf4-ΔCre Cox-1-/-/Ldlr-/- and Gp1ba-ΔCre Cox-1-/-/Ldlr-/- mice. In a mouse model of tail injury, Pf4-ΔCre-mediated and Gp1ba-ΔCre-mediated deletions of Cox-1 were similarly efficient in suppressing platelet prostanoid biosynthesis. Experimental thrombogenesis and attendant blood loss were similar in both models. However, the impact on atherogenesis was divergent, being accelerated in the Pf4-ΔCre mice while restrained in the Gp1ba-ΔCres. In the former, accelerated atherogenesis was associated with greater suppression of PGI2 biosynthesis, a reduction in the lipopolysaccharide-evoked capacity to produce PGE2 (prostaglandin E) and PGD2 (prostanglandin D), activation of the inflammasome, elevated plasma levels of IL-1ß (interleukin), reduced plasma levels of HDL-C (high-density lipoprotein receptor-cholesterol), and a reduction in the capacity for reverse cholesterol transport. By contrast, in the latter, plasma HDL-C and α-tocopherol were elevated, and MIP-1α (macrophage inflammatory protein-1α) and MCP-1 (monocyte chemoattractant protein 1) were reduced. CONCLUSIONS: Both approaches to Cox-1 deletion similarly restrain thrombogenesis, but a differential impact on Cox-1-dependent prostanoid formation by the vasculature may contribute to an inflammatory phenotype and accelerated atherogenesis in Pf4-ΔCre mice.

High-Density Artificial Synapse Array Consisting of Homogeneous Electrolyte-Gated Transistors.

The artificial synapse array with an electrolyte-gated transistor (EGT) as an array unit presents considerable potential for neuromorphic computation. However, the integration of EGTs faces the drawback of the conflict between the polymer electrolytes and photo-lithography. This study presents a scheme based on a lateral-gate structure to realize high-density integration of EGTs and proposes the integration of 100 × 100 EGTs into a 2.5 × 2.5 cm2 glass, with a unit density of up to 1600 devices cm-2 . Furthermore, an electrolyte framework is developed to enhance the array performance, with ionic conductivity of up to 2.87 × 10-3  S cm-1 owing to the porosity of zeolitic imidazolate frameworks-67. The artificial synapse array realizes image processing functions, and exhibits high performance and homogeneity. The handwriting recognition accuracy of a representative device reaches 92.80%, with the standard deviation of all the devices being limited to 9.69%. The integrated array and its high performance demonstrate the feasibility of the scheme and provide a solid reference for the integration of EGTs.

Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS / 法医学杂志

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Protective effect and mechanism of acellular nerve allografts combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury / 解剖学报

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

Simultaneous detection of 34 emerging contaminants in tap water by HPLC-MS/MS and health risk assessment / 中国法医学杂志

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

Deep phenotyping of the lipidomic response in COVID-19 and non-COVID-19 sepsis.

BACKGROUND: Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs-CoV-2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU). METHODS: Mass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity. RESULTS: Circulating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID-19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α-III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12-HETE, exhibited relative specificity for COVID-19 and correlated with sPLA2 and the interleukin-13 receptor to drive lymphopenia, a marker of disease severity. Pro-inflammatory eicosanoids remained correlated with severity in COVID-19 28 days after admission. Amongst non-COVID ICU patients, elevations in 5- and 15-HETE and 9- and 13-HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflected disease severity in COVID-19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non-B non-T cell activation. In COVID-19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids - ChoE 18:3, LPC-O-16:0 and PC-O-30:0 - were altered specifically in COVID. LPC-O-16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi-omic inflammatory pathways and disease severity. CONCLUSIONS: A broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12-HETE and the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients and correlate with the inflammatory response to link to disease severity.

Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis.

Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find a broad based lipidomic storm driven predominantly by secretory (s) phospholipase A 2 (sPLA 2 ) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD 2 and PGI 2 , and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.

The expansion of newborn neurons in hippocampus improves social recognition deficit in a mouse model of autism.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by core symptoms of impaired social interaction and communication. The pathological mechanism and treatment are not clear and need further study. Our previous study found that the deletion of high-risk gene Autism Susceptibility 2 (AUTS2) in mice led to dentate gyrus (DG) hypoplasia that highly associated with impaired social novelty recognition. Here we aim to improve the social deficit through increasing the neurogenesis in the subgranular zone (SGZ) and expanding the newborn granule neurons in DG. Methods: Three approaches including repeated oxytocin administration, feeding in enriched environment and overexpression of cyclin-dependent kinase 4 (Cdk4)-CyclinD1 complex in DG neural stem cells (NSCs) at the post-weaning stage were conducted. Results: We found that the number of EdU labeled proliferative NSCs or retrovirus labeled newborn neurons was significantly increased after manipulations. The social recognition deficit was also significantly improved. Discussion: Our findings suggested a possible strategy to restore the social deficit through expansion of newborn neurons in hippocampus, which might provide a new insight into the treatment of autism.

Sexual dimorphism in the response to chronic circadian misalignment on a high-fat diet.

Longitudinal studies associate shiftwork with cardiometabolic disorders but do not establish causation or elucidate mechanisms of disease. We developed a mouse model based on shiftwork schedules to study circadian misalignment in both sexes. Behavioral and transcriptional rhythmicity were preserved in female mice despite exposure to misalignment. Females were protected from the cardiometabolic impact of circadian misalignment on a high-fat diet seen in males. The liver transcriptome and proteome revealed discordant pathway perturbations between the sexes. Tissue-level changes were accompanied by gut microbiome dysbiosis only in male mice, biasing toward increased potential for diabetogenic branched chain amino acid production. Antibiotic ablation of the gut microbiota diminished the impact of misalignment. In the United Kingdom Biobank, females showed stronger circadian rhythmicity in activity and a lower incidence of metabolic syndrome than males among job-matched shiftworkers. Thus, we show that female mice are more resilient than males to chronic circadian misalignment and that these differences are conserved in humans.

Modulation of the Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination by Nonsteroidal Anti-Inflammatory Drugs.

Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related adverse effects, given the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine-specific receptor binding domain (RBD) IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here we report a series of divergent omics signals that invites additional hypotheses testing. SIGNIFICANCE STATEMENT: The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on the immune response elicited by repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunizations was profiled by immunophenotypic, proteomic, and metabolomic approaches in a clinical pilot study of small sample size. A SARS-CoV-2 vaccine-specific immune response was evident irrespective of concomitant NSAID consumption. The information gathered may inform the design of a definitive clinical trial.

Superconductivity in Mo4Ga20As with endohedral gallium clusters.

We report the discovery and detailed investigation of superconductivity in Mo4Ga20As. Mo4Ga20As crystallizes in a space group ofI4/m(No. 87), with the lattice parametersa= 12.86352 Å andc= 5.30031 Å. The resistivity, magnetization, and specific heat data reveal Mo4Ga20As to be a type-II superconductor withTc= 5.6 K. The upper and lower critical fields are estimated to be 2.78 T and 22.0 mT, respectively. In addition, electron-phonon coupling in Mo4Ga20As is possibly stronger than the BCS weak-coupling limit. First-principles calculations suggest the Fermi level being dominated by the Mo-4dand Ga-4porbitals.

An interaction effect of external noise and exposure duration on the spatial contrast sensitivity function.

It has been demonstrated that contrast sensitivity is sensitive to stimulus exposure duration. Here, we investigated how the duration effect on contrast sensitivity was modulated by the spatial frequency and intensity of external noise. Through a contrast detection task, the contrast sensitivity function under 10 spatial frequencies, three external noise, and two exposure duration conditions was measured. The temporal integration effect was defined by the difference in contrast sensitivity or the area under the log contrast sensitivity function between short and long exposure durations. We found that (1) the temporal integration effect was less pronounced in the zero-noise condition than in the low- or high-noise condition; (2) in the zero-noise condition, a stronger temporal integration effect was observed at high spatial frequencies; (3) in the high-noise condition, a stronger temporal integration effect was observed at low spatial frequencies; (4) the spatial-frequency-dependent transient or sustained mechanism is also sensitive to external noise level; and (5) perceptual template model analysis revealed that both decreased additive internal noise and an improved perceptual template accounted for the temporal integration effect, and these two factors were tuned to spatial frequency.

Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts

Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.

Identification of immune associated potential molecular targets in proliferative diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and causes of blindness in developed countries. Our study was designed to identify immune-related genes involved in the progression of proliferative diabetic retinopathy (PDR). METHODS: The "GSE102485" dataset of neovascular membrane samples (NVMs) from type 1 and 2 diabetes mellitus patients was downloaded from the Gene Expression Omnibus database. Functional enrichment analyses, protein-protein interaction network (PPI) construction, and module analysis of immune pathways in NVMs and controls were conducted via Gene Set Enrichment Analysis and Metascape. RESULTS: The significantly upregulated hallmark gene sets in DR2 and DR1 groups were involved in five immune pathways. Only CCR4, CXCR6, C3AR1, LPAR1, C5AR1, and P2RY14 were not previously reported in the context of PDR molecular pathophysiology. Except for P2RY14, all of the above were upregulated in retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) by quantitative Real Time Polymerase Chain Reaction (qRT-PCR). CONCLUSION: The genes identified herein provide insight into immune-related differential gene expression during DR progression.

Nonsteroidal anti-inflammatory drugs as a targeted therapy for bone marrow failure in Ghosal hematodiaphyseal dysplasia.

Advances in genomic diagnostics hold promise for improved care of rare hematologic diseases. Here, we describe a novel targeted therapeutic approach for Ghosal hematodiaphyseal dysplasia, an autosomal recessive disease characterized by severe normocytic anemia and bone abnormalities due to loss-of-function mutations in thromboxane A synthase 1 (TBXAS1). TBXAS1 metabolizes prostaglandin H2 (PGH2), a cyclooxygenase (COX) product of arachidonic acid, into thromboxane A2. Loss-of-function mutations in TBXAS result in an increase in PGH2 availability for other PG synthases. The current treatment for Ghosal hematodiaphyseal dysplasia syndrome consists of corticosteroids. We hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and COX-2, could ameliorate the effects of TBXAS1 loss and improve hematologic function by reducing prostaglandin formation. We treated 2 patients with Ghosal hematodiaphyseal dysplasia syndrome, an adult and a child, with standard doses of NSAIDs (aspirin or ibuprofen). Both patients had rapid improvements concerning hematologic parameters and inflammatory markers without adverse events. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenia, and should be considered for first-line treatment for Ghosal hematodiaphyseal dysplasia syndrome.