Efficient Electrochemical Microsensor for the Simultaneous Measurement of Hydrogen Peroxide and Ascorbic Acid in Living Brains.

Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 µM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.

CircHIVEP2 alleviates Parkinson's nerve damage and inflammatory response by targeting miR-485-3p.

OBJECTIVE: Dysregulation of covalently closed circular RNAs (circRNAs) has been associated with neurological disorders, the role of circHIVP2 in Parkinson's disease (PD) and its molecular mechanism is not well understood. METHODS: 127 patients with PD and 85 healthy people were enrolled. RT-qPCR was employed to examine the levels of circHIVEP2. ROC curve to explore the diagnostic. Mpp+ induced the SH-SY5Y to construct an in vitro PD cell model. Cell viability, apoptosis, and secretion levels of inflammatory factors were analyzed by CCK-8, flow cytometry, and ELISA assay. CircHIVEP2 targets miRNA predicted by bioinformatics database and validated by the dual luciferase reporter and RIP assays. RESULTS: CircHIVEP2 was typically lower in PD patients than in controls. CircHIVEP2 has certain specificity and sensitivity to recognize PD patients from healthy individuals. miR-485-3p, a target miRNA of circHIVEP2, was significantly elevated in PD patients. Additionally, MPP+ induction reduced cell viability and promoted apoptosis and inflammatory factor overproduction. However, overexpression of circHIVEP2 significantly inhibited the effects of MPP+, but this inhibition was significantly attenuated by elevated miR-485-3p. CONCLUSION: circHIVEP2 is a potential diagnostic biomarker for PD, and its upregulation mitigated MPP+-induced nerve damage and inflammation and this may be through targeted by the miR-485-3p.

Ru doped NiMoO4 nanoarray as a high-efficiency electrocatalyst for nitrite reduction to ammonia.

The electrocatalytic reduction of nitrite to recyclable ammonia (NH3) is essential to maintain nitrogen balance and meet growing energy requirements. Herein, we report that Ru doped honeycomb NiMoO4 nanosheet with copious oxygen vacancies grown on nickel foam substrate has been prepared by a facile hydrothermal synthesis and immersion process, which can act as an efficient electrocatalyst for NH3 synthesis by reduction of nitrite. By optimizing the concentration of RuCl3 solution, 0.01Ru-NiMoO4/NF possesses excellent NO2-RR performance with NH3 yield of 20249.17 ± 637.42 µg h-1 cm-2 at -0.7 V and FE of 95.56 ± 0.72 % at -0.6 V. When assembled into a Zn-NO2- battery, it provides a remarkable level of power density of 13.89 mW cm-2, outperforming the performance of virtually all previous reports. The efficient adsorption and activation of NO2- over Ru-doped NiMoO4 with oxygen vacancy have been verified by density functional theory calculations, as well as the possible reaction pathway.

DIRECT: Digital Microfluidics for Isolation-Free Shared Library Construction of Single-Cell DNA Methylome and Transcriptome.

Simultaneous profiling of DNA methylation and gene expression within single cells is a powerful technology to dissect complex gene regulatory network of cells. However, existing methods are based on picking a single-cell in a tube and split single-cell lysate into two parts for transcriptome and methylome library construction, respectively, which is costly and cumbersome. Here, DIRECT is proposed, a digital microfluidics-based method for high-efficiency single-cell isolation and simultaneous analysis of the methylome and transcriptome in a single library construction. The accuracy of DIRECT is demonstrated in comparison with bulk and single-omics data, and the high CpG site coverage of DIRECT allows for precise analysis of copy number variation information, enabling expansion of single cell analysis from two- to three-omics. By applying DIRECT to monitor the dynamics of mouse embryonic stem cell differentiation, the relationship between DNA methylation and changes in gene expression during differentiation is revealed. DIRECT enables accurate, robust, and reproducible single-cell DNA methylation and gene expression co-analysis in a more cost-effective, simpler library preparation and automated manner, broadening the application scenarios of single-cell multi-omics analysis and revealing a more comprehensive and fine-grained map of cellular regulatory landscapes.

Changes in sensory characteristics, chemical composition and microbial succession during fermentation of ancient plants Pu-erh tea.

"Ancient tea plants" are defined as tea trees > 100 years old, or with a trunk diameter > 25 cm; their leaves are manufactured to high - quality, valuable ancient plants pu-erh tea (APPT). In this study, a fermentation of APPT were developed, and outstanding sweetness of APPT infusion was observed. During fermentation, the content of soluble sugars, theabrownins (p < 0.05), as well as 41 metabolites were increased [Variable importance in projection (VIP) > 1.0; p < 0.05 and Fold-change (FC) FC > 2]; While relative levels of 72 metabolites were decreased (VIP > 1.0, p < 0.05 and FC < 0.5. Staphylococcus, Achromobacter, Sphingomonas, Thermomyces, Rasamsonia, Blastobotrys, Aspergillus and Cladosporium were identified as dominant genera, and their relative levels were correlated with contents of characteristic components (p < 0.05). Together, changes in sensory characteristics, chemical composition and microbial succession during APPT fermentation were investigated, and advanced the formation mechanism of its unique quality.

Ultra-high static magnetic fields cause immunosuppression through disrupting B-cell peripheral differentiation and negatively regulating BCR signaling.

To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra-high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment.

Effects of Cooking Processes on Protein Nutritional Values and Volatile Flavor Substances of Silver Carp (Hypophthalmichthys molitrix).

Silver carp (Hypophthalmichthys molitrix) is normally cooked at a high temperature. In order to explore the effects of cooking methods on the protein nutritional values and volatile flavor substances of silver carp meat, the meat was fried, roasted and steamed, and its contents were determined in relation to moisture, protein, fat, ash, amino acids and volatile flavor substances. The results show that the moisture content of cooked silver carp can be ranked as follows: raw > steamed > roasted > fried. The protein content order of the four samples can be ranked: fried > roasted > raw > steamed. The ash and the fat contents of the four samples showed similar significant (p < 0.05) differences, in the order of fried > roasted > steamed > raw. The contents of all the amino acids in the fried meat were significantly (p < 0.05) higher than the contents in others, and the frying, roasting and steaming processes improved the umami taste (supported by the increased content of glutamate and aspartate) and the protein nutritional value (supported by the amino acid score, essential amino acid index and protein efficiency ratio) of the silver carp meat. A total of 51 compounds were detected in the fried, roasted and steamed meat. Frying and roasting reduced the fishy flavor of this meat. The odor activity value (OAV) indicated that methanethiol, 1-octen-3-ol and 2-heptanone were the key flavor chemicals in raw meat. Hexanal, propionaldehyde, octanal, nonanal, decanal, 1-octen-3-ol and 2-heptanone were key to the flavor of fried meat. Pentanal, decanal, methyl mercap-tan and 1-octen-3-ol contributed greatly to the overall flavor of the roasted meat. Nonanal, methylmercaptan and 1-octene-3-ol had strong effects on the flavor of the steamed silver carp meat.

DDX24 Mutation Alters NPM1 Phase Behavior and Disrupts Nucleolar Homeostasis in Vascular Malformations.

Point mutations in the DEAD-box helicase DDX24 are associated with vascular malformations such as multi-organ venous and lymphatic defect (MOVLD) syndrome and Budd-Chiari syndrome, with the pathogenesis largely uncharacterized. DDX24 is mainly located in the nucleolus, where nucleophosmin (NPM1) regulates nucleolar homeostasis via liquid-liquid phase separation (LLPS). However, the connection between DDX24 and NPM1 in vascular malformation remains elusive. Here we demonstrated that DDX24 formed biomolecular condensates in vitro and the mutated DDX24 protein, DDX24E271K, partitioned less into the nucleoli in tissues from patients with MOVLD syndrome and cultured endothelial cells (ECs), altering nucleolar morphology. Furthermore, DDX24 was directly associated with NPM1 to regulate its phase behavior as a client in the nucleolar granular component (GC). Functionally, we showed that DDX24 was essential in maintaining nucleolar homeostasis of ECs and that either mutation or knockdown of DDX24 led to the dysfunction of ribosome biogenesis and the elevated capability of cell migration and tube formation. Our findings illustrate how DDX24 mutation affects nucleolar structure and function by regulating the phase behavior of NPM1 in the setting of vascular malformation.

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD). Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining. Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms. Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Genomes to Fields 2022 Maize genotype by Environment Prediction Competition.

OBJECTIVES: The Genomes to Fields (G2F) 2022 Maize Genotype by Environment (GxE) Prediction Competition aimed to develop models for predicting grain yield for the 2022 Maize GxE project field trials, leveraging the datasets previously generated by this project and other publicly available data. DATA DESCRIPTION: This resource used data from the Maize GxE project within the G2F Initiative [1]. The dataset included phenotypic and genotypic data of the hybrids evaluated in 45 locations from 2014 to 2022. Also, soil, weather, environmental covariates data and metadata information for all environments (combination of year and location). Competitors also had access to ReadMe files which described all the files provided. The Maize GxE is a collaborative project and all the data generated becomes publicly available [2]. The dataset used in the 2022 Prediction Competition was curated and lightly filtered for quality and to ensure naming uniformity across years.

NiMoO4 nanorods with oxygen vacancies self-supported on Ni foam towards high-efficiency electrocatalytic conversion of nitrite to ammonia.

As an eco-friendly and sustainable strategy, the electrochemical reduction of nitrite (NO2-) can simultaneous generation of NH3 and treatment of NO2- contamination in the environment. Herein, monoclinic NiMoO4 nanorods with abundant oxygen vacancies self-supported on Ni foam (NiMoO4/NF) are considered high-performance electrocatalysts for ambient NH3 synthesis by reduction of NO2-, which can deliver an outstanding yield of 18089.39 ± 227.98 µg h-1 cm-2 and a preferable FE of 94.49 ± 0.42% at -0.8 V. Additionally, its performance remains relatively stable during long-term operation as well as cycling tests. Furthermore, density functional theory calculations unveil the vital role of oxygen vacancies in promoting nitrite adsorption and activation, ensuring efficient NO2-RR towards NH3. A Zn-NO2- battery with NiMoO4/NF as the cathode shows high battery performance as well.

Phosphoproteomic analysis on ovarian follicles reveals the involvement of LSD1 phosphorylation in Chicken follicle selection.

BACKGROUND: Follicle selection in chickens refers to the process of selecting one follicle from a group of small yellow follicles (SY, 6-8 mm in diameter) for development into 12-15 mm hierarchal follicles (usually F6 follicles), which is controlled by sex hormones including follicle-stimulating factor (FSH), estrogen and progesterone. Follicle selection is a critical process impacting egg production in chicken, therefore, is the focus of many studies. Phosphorylation is important for the proper function of proteins, thus, needs to be analyzed by proteomic level. RESULT: In this study, we compared the phosphoproteomes of SY and F6 follicles in laying hens and identified 2,386 phosphoproteins and 5,940 phosphosites, of which 4,235 sites of 1,963 phosphoproteins were quantified. From SY to F6 follicles, 190 phosphorylation sites of 149 proteins changed significantly, among which the phosphorylation level of lysine demethylase 1 A (LSD1) at the conserved 54th serine (LSD1Ser54p) was significantly upregulated in F6 follicles compared to SY follicles (p < 0.05); however, the expression of chicken LSD1 were not significantly different on both mRNA and protein levels. LSD1Ser54p is mainly located in the nucleus of both SY and F6 follicles, and was higher in F6 follicles than that of SY follicles revealed by both immunofluorescence and Western blotting. LSD1Ser54p level increased after treatment with 5 ng/mL and 10 ng/mL of FSH in the theca cells and the granulosa cells of pre-hierarchal follicles, and with 50 ng/mL in granulosa cells of hierarchal follicles. In the theca cells of hierarchal follicles, estrogen stimulated the level of LSD1Ser54p in a dosage-dependent manner, and in granulosa cells of pre-hierarchal follicles, 10 ng/mL of estrogen increased LSD1Ser54p expression. Treatment with 50 ng/mL of progesterone increased LSD1Ser54p expression in theca cells of pre-hierarchal follicles, and with 10 to 100 ng/ml enhanced LSD1Ser54p expression in the granulosa cells of hierarchal follicles. CONCLUSION: The expression dynamics of LSD1Ser54p in follicles from SY to F6 and its regulation by sex hormones suggest that it is involved in chicken follicle selection.

An In Vitro Catalysis of Tea Polyphenols by Polyphenol Oxidase.

Tea polyphenol (TPs) oxidation caused by polyphenol oxidase (PPO) in manufacturing is responsible for the sensory characteristics and health function of fermented tea, therefore, this subject is rich in scientific and commercial interests. In this work, an in vitro catalysis of TPs in liquid nitrogen grinding of sun-dried green tea leaves by PPO was developed, and the changes in metabolites were analyzed by metabolomics. A total of 441 metabolites were identified in the catalyzed tea powder and control check samples, which were classified into 11 classes, including flavonoids (125 metabolites), phenolic acids (67 metabolites), and lipids (55 metabolites). The relative levels of 28 metabolites after catalysis were decreased significantly (variable importance in projection (VIP) > 1.0, p < 0.05, and fold change (FC) < 0.5)), while the relative levels of 45 metabolites, including theaflavin, theaflavin-3'-gallate, theaflavin-3-gallate, and theaflavin 3,3'-digallate were increased significantly (VIP > 1.0, p < 0.05, and FC > 2). The increase in theaflavins was associated with the polymerization of catechins catalyzed by PPO. This work provided an in vitro method for the study of the catalysis of enzymes in tea leaves.

Gradient hydrogel actuator with fast response and self-recovery in air.

The driving principle of a thermal-responsive hydrogel that loses water at high temperature and absorbs water at low temperature limits its application in an aqueous environment. Here, a gradient hydrogel actuator was developed by introducing sodium hyaluronate into poly(N-isopropylacrylamide) hydrogel by an asymmetric mold method. The hydrogel exhibited a fast response above the LCST in air and unusual self-recovery without the need for further temperature stimuli. The actuation behavior was related to conversion from free water to bound water and water retention within the gradient matrix. The self-recovery mechanism was explored. This work provides a new insight into designing bionic hydrogels applied in a non-aqueous environment.

Serum amyloid P component (SAP) modulates antidepressant effects through promoting membrane insertion of the serotonin transporter.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits including those in Alzheimer's disease. SAP has been observed to be elevated in patients with depression, and higher SAP levels are associated with better response to the antidepressant escitalopram. The mechanisms underlying these clinical observations remain unclear. We examined the effect of SAP on serotonin transporter (SERT) expression and localization using Western blot, confocal microscopy, and positron emission tomography with the radioligand [11C]DASB. We also investigated the effect of SAP on treatment response to escitalopram in mice with the forced swim test (FST), a classical behaviour paradigm to assess antidepressant effects. SAP reduced [11C]DASB binding as an index of SERT levels, consistent with Western blots showing decreased total SAP protein because of increased protein degradation. In conjunction with the global decrease in SERT levels, SAP also promotes VAMP-2 mediated SERT membrane insertion. SAP levels are correlated with behavioural despair and SSRI treatment response in mice with FST. In MDD patients, the SAP and membrane SERT levels are correlated with response to SSRI treatment. SAP has complex effects on SERT levels and localization, thereby modulating the effect of SSRIs, which could partially explain clinical variability in antidepressant treatment response. These results add to our understanding of the mechanism for antidepressant drug action, and with further work could be of clinical utility.

Morphology-Controlled Synthesis of V1.11S2 for Electrocatalytic Hydrogen Evolution Reaction in Acid Media.

High-performance low-cost catalysts are in high demand for the hydrogen evolution reaction (HER). In the present study, we reported that V1.11S2 materials with flower-like, flake-like, and porous morphologies were successfully synthesized by hydrothermal synthesis and subsequent calcination. The effects of morphology on hydrogen evolution performance were studied. Results show that flower-like V1.11S2 exhibits the best electrocatalytic activity for HER, achieving both high activity and preferable stability in 0.5 M H2SO4 solution. The main reason can be ascribed to the abundance of catalytically active sites and low charge transfer resistance.

Higher serum albumin-corrected calcium levels are associated with revascularization and poor outcome after mechanical thrombectomy.

BACKGROUND: Serum calcium abnormalities have been determined to be associated with the risk and outcome of stroke. The aim of the present study was to examine the associations of serum calcium with vascular recanalization, symptomatic intracranial haemorrhage and functional outcome in stroke patients after mechanical thrombectomy. METHODS: A total of 192 patients treated with mechanical thrombectomy for anterior circulation large vessel occlusion were consecutively included from August 2017 to June 2021. Serum calcium levels were measured on admission, and albumin-corrected calcium levels were calculated for subsequent analysis. Successful arterial revascularization was defined as a modified Thrombolysis in Cerebral Infarction scale score ≥ 2b. Symptomatic intracranial haemorrhage was assessed according to the European Cooperative Acute Stroke Study (ECASS) III criteria. Poor functional outcome was defined as a modified Rankin Scale score > 2 at 3 months. RESULTS: Patients with poor outcomes had higher albumin-corrected calcium levels than patients with good outcomes before (2.20 (2.10, 2.30) mmol/L vs. 2.13 (2.04, 2.24) mmol/L, P = 0.002), and after adjusting for other factors (AOR 95% CI, 1.812 (1.253, 2.621), P = 0.002). Patients with unsuccessful recanalization had higher albumin-corrected calcium levels than those with recanalization (2.26 (2.09, 2.46) mmol/L vs. 2.17 (2.07, 2.27) mmol/L, P = 0.029), and after adjusting for other factors (AOR 95% CI, 2.068 (1.214, 3.524)), P = 0.008). No association was found between albumin-corrected calcium and symptomatic intracranial haemorrhage. CONCLUSIONS: Higher serum albumin-corrected calcium levels are independently associated with revascularization and poor outcome in stroke patients after mechanical thrombectomy.

Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model.

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound-target-pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4'-sulfate, tectoridin-4'-sulfate, and 6″-O-xylosyltectoridin-4'-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.

High-Efficiency Ammonia Electrosynthesis on Anatase TiO2-x Nanobelt Arrays with Oxygen Vacancies by Selective Reduction of Nitrite.

Electrocatalytic reduction of nitrite to NH3 provides a new route for the treatment of nitrite in wastewater, as well as an attractive alternative to NH3 synthesis. Here, we report that an oxygen vacancy-rich TiO2-x nanoarray with different crystal structures self-supported on the Ti plate can be prepared by hydrothermal synthesis and by subsequently annealing it in an Ar/H2 atmosphere. Anatase TiO2-x (A-TiO2-x) can be a superb catalyst for the efficient conversion of NO2- to NH3; a high NH3 yield of 12,230.1 ± 406.9 µg h-1 cm-2 along with a Faradaic efficiency of 91.1 ± 5.5% can be achieved in a 0.1 M NaOH solution containing 0.1 M NaNO2 at -0.8 V, which also exhibits preferable durability with almost no decay of catalytic performances after cycling tests and long-term electrolysis. Furthermore, a Zn-NO2- battery with such A-TiO2-x as a cathode delivers a power density of 2.38 mW cm-2 as well as a NH3 yield of 885 µg h-1 cm-2.